tag:theconversation.com,2011:/us/topics/genes-3429/articlesGenes – The Conversation2024-03-01T00:39:18Ztag:theconversation.com,2011:article/2222642024-03-01T00:39:18Z2024-03-01T00:39:18ZCurious Kids: what are the main factors in forming someone’s personality?<figure><img src="https://images.theconversation.com/files/577829/original/file-20240226-24-q8fp4p.jpg?ixlib=rb-1.1.0&rect=0%2C11%2C7348%2C4891&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/casual-children-cheerful-cute-friends-kids-499922971">Rawpixel.com/Shutterstock</a></span></figcaption></figure><p><strong>“What are the main factors in forming someone’s personality?” – Emma, age 10, from Shanghai</strong></p>
<p><a href="https://theconversation.com/au/topics/curious-kids-36782"><img src="https://images.theconversation.com/files/291898/original/file-20190911-190031-enlxbk.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=90&fit=crop&dpr=1" width="100%"></a></p>
<p>Hello Emma, and thank you for this very interesting question!</p>
<p>Let’s start by exploring what we mean by personality. Have you noticed no two people are completely alike? We all see, experience, and understand the world in different ways. </p>
<p>For example, some people love spending time with friends and being the centre of attention, whereas other people are more shy and enjoy having time to themselves. </p>
<p>Your unique personality is shaped by your genes as well as various influences in your environment. And your personality plays an important role in how you interact with the world.</p>
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<strong>
Read more:
<a href="https://theconversation.com/curious-kids-how-did-the-first-person-evolve-142735">Curious Kids: how did the first person evolve?</a>
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</em>
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<h2>The big five</h2>
<p>Did you know there are scientists who spend time researching personality? Their research is concerned with describing the ways <a href="https://www.annualreviews.org/doi/abs/10.1146/annurev.psych.093008.100507">people differ from each other</a>, and understanding how these differences could be important for other parts of life such as our health and how well we do in school or at work.</p>
<p>There are many different perspectives on personality. A widely accepted viewpoint based on <a href="https://www.sciencedirect.com/science/article/abs/pii/S0092656620301367?via%3Dihub">a lot of research</a> is called the five factor model or the “big five”. According to this theory, a great deal of a person’s personality can be summarised in terms of where they sit on five dimensions, called traits:</p>
<ol>
<li><p>the <strong>introversion-extraversion</strong> trait refers to how much someone is outgoing and social (extroverted) or prefers being with smaller groups of friends or focusing on their own thoughts (introverted)</p></li>
<li><p><strong>agreeableness</strong> captures how much someone tends to be cooperative and helps others</p></li>
<li><p><strong>openness to experience</strong> refers to how much a person is creative and enjoys experiencing new things</p></li>
<li><p><strong>neuroticism</strong> describes a person’s tendency to experience negative feelings, like worrying about things that could go wrong</p></li>
<li><p><strong>conscientiousness</strong> encompasses how much a person is organised, responsible, and dedicated to things that are important to them, like schoolwork or training for a sports team. </p></li>
</ol>
<p>A person can have high, low, or moderate levels of each of these traits. And understanding whether someone has higher or lower levels of the big five can tell us a lot about how we might expect them to behave in different situations.</p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/curious-kids-how-does-our-dna-relate-to-our-personality-and-appearance-168489">Curious Kids: how does our DNA relate to our personality and appearance?</a>
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</em>
</p>
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<h2>So what shapes our personalities?</h2>
<p>A number of factors shape <a href="https://www.annualreviews.org/doi/10.1146/annurev-psych-010418-103244">our personalities</a>, including our genes and social environment. </p>
<p>Our bodies are made up of many very small structures called cells. Within these cells are genes. We inherit genes from our parents, and they carry the information needed to make our bodies and personalities. So, your personality may be a bit like your parents’ personalities. For example, if you’re an outgoing sort of person who loves to meet new people, perhaps one or both of your parents are very social too.</p>
<figure class="align-center ">
<img alt="A mother getting her son ready, fastening his backpack." src="https://images.theconversation.com/files/577830/original/file-20240226-16-1uvanq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/577830/original/file-20240226-16-1uvanq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=397&fit=crop&dpr=1 600w, https://images.theconversation.com/files/577830/original/file-20240226-16-1uvanq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=397&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/577830/original/file-20240226-16-1uvanq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=397&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/577830/original/file-20240226-16-1uvanq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=499&fit=crop&dpr=1 754w, https://images.theconversation.com/files/577830/original/file-20240226-16-1uvanq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=499&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/577830/original/file-20240226-16-1uvanq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=499&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Our personalities are influenced by the genes we get from our parents.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/mother-dressing-her-child-getting-ready-2012433464">KieferPix/Shutterstock</a></span>
</figcaption>
</figure>
<p>Personalities are also affected by our environment, such as our experiences and our relationships with family and friends. For example, <a href="https://www.sciencedirect.com/science/article/pii/S0165178102001282">some research has shown</a> our relationships with our parents can influence our personality. If we have loving and warm relationships, we may be more agreeable and open. But if our relationships are hurtful or stressful, this may increase our neuroticism. </p>
<p><a href="https://bpspsychub.onlinelibrary.wiley.com/doi/full/10.1111/bjdp.12102">Another study</a> showed that, over time, young children who were more physically active were less introverted (less shy) and less likely to get very upset when things don’t go their way, compared to children who were less physically active. Although we don’t know why this is for sure, one possible explanation is that playing sport leads to reduced shyness because it introduces children to different people.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/curious-kids-why-do-some-people-worry-more-than-others-119874">Curious Kids: why do some people worry more than others?</a>
</strong>
</em>
</p>
<hr>
<p>While we’re learning more about personality development all the time, research in this area presents quite a few challenges. Many different biological, cultural and environmental influences shape our development, and these factors can interact with each other <a href="https://www.annualreviews.org/doi/abs/10.1146/annurev-psych-010213-115100">in complex ways</a>. </p>
<h2>Is our personality fixed once we become adults?</h2>
<p>Although we develop most of our personality when we are young, and people’s personalities tend to become more stable as they get older, it is possible for aspects of a person’s personality to change, even when they are fully grown. </p>
<p>A good example of this can be seen among people who seek treatment for conditions like anxiety or depression. People who respond well to working with a psychologist can show <a href="https://onlinelibrary.wiley.com/doi/10.1002/cpp.2541">decreases in neuroticism</a>, indicating they become less likely to worry a lot or feel strong negative feelings when something stressful happens.</p>
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<p><em>Hello, Curious Kids! Do you have a question you’d like an expert to answer? Ask an adult to send your question to curiouskids@theconversation.edu.au</em></p><img src="https://counter.theconversation.com/content/222264/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Tim Windsor receives funding from the Australian Research Council. </span></em></p><p class="fine-print"><em><span>Natalie Goulter receives funding from the National Health and Medical Research Council. </span></em></p>Personality is shaped by our genes and various influences in our social environments, and it plays an important role in how we interact with the world.Tim Windsor, Professor, Director, Generations Research Initiative, College of Education, Psychology and Social Work, Flinders UniversityNatalie Goulter, Lecturer, College of Education, Psychology and Social Work, Flinders UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2230682024-02-20T19:37:25Z2024-02-20T19:37:25ZCanada’s Genetic Non-Discrimination Act has only had a limited impact on the use of genetic information by life insurers<figure><img src="https://images.theconversation.com/files/575694/original/file-20240214-20-o0yrke.jpg?ixlib=rb-1.1.0&rect=0%2C31%2C4256%2C2790&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Collecting genetic information for the purposes of determining life insurance protections could lead to genetic discrimination.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>The advancement of genetic technologies in the past three decades has spotlighted the urgent need to address genetic discrimination. Genetic discrimination is the differential adverse treatment or unfair profiling of an individual relative to the rest of the population <a href="https://www.facetsjournal.com/doi/10.1139/facets-2023-0101">based on actual or presumed genetic information</a>. </p>
<p>If not regulated, genetic discrimination has the potential to infringe on people’s privacy and fundamental freedoms. This in turn may deter people from accessing clinical genetic services and testing based on concerns about how their personal information may be used.</p>
<p>Evidence from a growing number of countries shows that a person’s genetic information can be misused by third parties. A person may be refused employment or <a href="https://theconversation.com/life-insurers-can-charge-more-or-decline-cover-based-on-your-genetic-test-results-new-laws-must-change-this-212183">insurance</a> based on an assumption that they may develop a life-threatening disease.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/576037/original/file-20240215-24-m5aodk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="ALT" src="https://images.theconversation.com/files/576037/original/file-20240215-24-m5aodk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/576037/original/file-20240215-24-m5aodk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/576037/original/file-20240215-24-m5aodk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/576037/original/file-20240215-24-m5aodk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/576037/original/file-20240215-24-m5aodk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/576037/original/file-20240215-24-m5aodk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/576037/original/file-20240215-24-m5aodk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The widespread availability of genetic testing poses new risks for consumers.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<h2>New avenues for discrimination</h2>
<p>While instances of genetic discrimination have primarily arisen in the context of life insurance, the wider use of genetic testing and data usage in non-health settings has introduced new avenues for discrimination to occur. </p>
<p>Recently, genetic discrimination has taken on many forms, with reports emerging in <a href="https://doi.org/10.1177/0034523719869956">education</a>, access to <a href="https://ssrn.com/abstract=2973255">property</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/34366728">sports</a>, <a href="https://doi.org/10.1038/sj.ejhg.5201937">adoption</a> and <a href="https://doi.org/10.1097/hrp.0000000000000141">crime prevention</a>.</p>
<p>In an effort to prevent genetic discrimination and advance research, the Canadian Parliament adopted the <a href="https://laws-lois.justice.gc.ca/eng/annualstatutes/2017_3/page-1.html">Genetic Non-Discrimination Act</a> (GNDA) in 2017. Broadly understood, the GNDA prohibits the imposition and use of genetic test results as a condition to access goods and services. </p>
<p>The GNDA also makes “genetic characteristics” a prohibited ground for discrimination under the <a href="https://www.chrc-ccdp.gc.ca/en/node/723">Canadian Human Rights Act</a> and prohibits the use of genetic testing in matters of employment under the <a href="https://laws-lois.justice.gc.ca/eng/acts/l-2/page-34.html#:%7E:text=247.98%20(1)%20The%20following%20definitions%20apply%20in%20this%20Division.&text=(2)%20Every%20employee%20is%20entitled,to%20undergo%20a%20genetic%20test.&text=(3)%20Every%20employee%20is%20entitled,results%20of%20a%20genetic%20test.">Canadian Labour Code</a>.</p>
<p>After a series of revisions, debates and legal challenges, the GNDA was <a href="https://www.cbc.ca/news/politics/stefanovich-supreme-court-of-canada-genetic-information-1.5643245">finally confirmed in 2020 by the Supreme Court of Canada</a>.</p>
<h2>A modest impact</h2>
<p>Our research at McGill University’s <a href="https://www.genomicsandpolicy.org/">Centre of Genomics and Policy</a> investigated the impact of the GNDA. We focused on genetic discrimination in the context of purchasing life insurance coverage from private insurers — an area that has received significant attention in genetic discrimination literature. </p>
<p>We found that the <a href="https://www.facetsjournal.com/doi/full/10.1139/facets-2023-0101">GNDA has had only a modest impact</a> on <a href="https://www.usatoday.com/money/blueprint/insurance/what-is-insurance-underwriting/">the underwriting practices</a> of Canadian life insurance companies. The researchers reviewed 16 application forms, accounting for almost 50 per cent of the life insurance companies in Québec.</p>
<p>The study demonstrated that, while a small number of companies are taking steps to comply with the GNDA, the impact of the law on the industry as a whole has been limited. Only four companies explicitly stated that applicants should not submit genetic test results. </p>
<p>The study also confirmed that it is possible for life insurers to circumvent the law by asking broadly phrased questions regarding genetic information that would not qualify as “results,” prompting voluntary submission of genetic results.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/576095/original/file-20240215-26-m2z2lh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="a couple sit across from a doctor in a white coat" src="https://images.theconversation.com/files/576095/original/file-20240215-26-m2z2lh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/576095/original/file-20240215-26-m2z2lh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/576095/original/file-20240215-26-m2z2lh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/576095/original/file-20240215-26-m2z2lh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/576095/original/file-20240215-26-m2z2lh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/576095/original/file-20240215-26-m2z2lh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/576095/original/file-20240215-26-m2z2lh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Life insurance companies sometimes solicit information in a manner that could prompt applicants to provide genetic information.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<h2>Preventing genetic discrimination</h2>
<p>While the GNDA marks an important first step in curtailing the spread of genetic discrimination, it appears that further steps will be necessary to prevent it. </p>
<p>Our study also raises fundamental questions about the opacity of the practices of the personal insurance industry in Canada, the limits of data protection legislation and the need to consider the potential discriminatory impact of third parties’ use of predictive health data in general. </p>
<p>We recommend the adoption of provincial regulations to provide more comprehensive protections, beyond those in the GNDA. Inclusive societal conversations and debate are also needed to further identify and design additional safeguards against discrimination. </p>
<p>Ultimately, given the lack of clarity around practices of insurers, there is a need for dialogue with the <a href="https://www.clhia.ca/">Canadian Life and Health Insurance Association</a> to encourage greater transparency around the underwriting process.</p><img src="https://counter.theconversation.com/content/223068/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Diya Uberoi receives funding from Genome Canada. </span></em></p><p class="fine-print"><em><span>Yann Joly receives funding from Genome Canada. </span></em></p>Canada needs additional regulation, developed through public consultations, stakeholder collaborations and community partnerships, to help regulate genetic testing and prevent genetic discrimination.Diya Uberoi, Academic Associate, Centre of Genomics and Policy, McGill UniversityYann Joly, James McGill Professor, Department of Human Genetics and Health Sciences, McGill UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2222962024-02-05T16:13:03Z2024-02-05T16:13:03ZA new virus-like entity has just been discovered – ‘obelisks’ explained<figure><img src="https://images.theconversation.com/files/573101/original/file-20240202-31-42ohg4.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C8038%2C5354&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/rear-view-male-doctor-taking-bodily-1510584707">Andrey_Popov/Shutterstock</a></span></figcaption></figure><p>Biological entities called obelisks have been hiding – in large numbers – inside the human mouth and gut. These microscopic entities, which were recently discovered by a team at Stanford University, are circular bits of genetic material that contain one or two genes and self-organise into a rod-like shape. </p>
<p>Although the study is still in <a href="https://www.biorxiv.org/content/10.1101/2024.01.20.576352v1">preprint</a> form, meaning that it has not been peer-reviewed, it has already been extensively written about, including in two heavyweight journals: <a href="https://www.nature.com/articles/d41586-024-00266-7">Nature</a> and <a href="https://www.science.org/content/article/it-s-insane-new-viruslike-entities-found-human-gut-microbes">Science</a>.</p>
<p>Let’s delve deeper into the strange world of very tiny “lifeforms”.</p>
<p>In biology, as in physics, things can get weirder and the rules fuzzier as we move through smaller and smaller scales. </p>
<p>Viruses, being unable to replicate without the help of a host, can most generously be considered to be on the edge of what constitutes life. Yet the estimated <a href="https://www.nationalgeographic.com/science/article/factors-allow-viruses-infect-humans-coronavirus">10 nonillion (one followed by 31 zeroes) individual viruses</a> on the planet can be found in every conceivable habitat and, through infecting and manipulating their hosts, have probably affected the evolutionary trajectories of all life. </p>
<p>Peering even further down into the world of minuscule biological entities, are the viroids – tiny scraps of genetic material (DNA-like molecules known as RNA) that cannot make proteins and, unlike viruses, don’t have a protective shell to encase their genome. </p>
<p>Viroids are examples of ribozymes: RNA molecules that may be a distant echo of the very first self-replicating genetic elements from which cellular life emerged. </p>
<p>Viroids can self-cleave (chop up) and re-ligate (stick back together) their genome as part of the replication cycle. And, despite their simplicity, they can cause serious disease in <a href="https://pubmed.ncbi.nlm.nih.gov/33801996/">flowering plants</a>.</p>
<h2>Between a virus and a viroid – perhaps</h2>
<p>The new <a href="https://www.biorxiv.org/content/10.1101/2024.01.20.576352v1.full">preprint</a> describes “viroid-like colonists of human microbiomes”. If “viroid-like” sounds non-committal, that is entirely deliberate. The newly discovered biological entity falls somewhere between viruses and viroids. </p>
<p>In fact, the name obelisks was proposed not only because of their shape, but also to provide wiggle room in case they turn out to be more like RNA plasmids (a different type of genetic element that resides inside bacteria) than either viruses or viroids.</p>
<p>Like viroids, obelisks have a circular single-stranded RNA genome and no protein coat but, like viruses, their genomes contain genes that are predicted to code for proteins. </p>
<p>All obelisks so far described encode a single major protein known as obulin, and many encode a second, smaller obulin. </p>
<p>Obulins bear no evolutionary resemblance, or “homology”, to any other protein found, and there are few clues as to their function. </p>
<p>By analysing existing datasets taken from the gut and mouth of humans as well as other diverse sources, the Stanford team found almost 30,000 distinct obelisk types. </p>
<p>These obelisk genomes have been previously overlooked because they are so dissimilar to anything described previously. The Stanford team found them using a clever bespoke method for searching databases for single-stranded circular RNA molecules to fish out any viroid-like elements. </p>
<p>It is clear from their results that obelisks are not rare. The researchers found them in datasets spanning the globe and in diverse niches. </p>
<p>These elements were detected in around 7% of microbiome datasets from the human gut and 50% of datasets from the mouth. However, whether these datasets provide a true representation of the prevalence and distribution of obelisks is unclear. </p>
<p>Different obelisk types were found in different body sites and in different donors. Long-term data revealed that people can harbour a single obelisk type for around a year. </p>
<p>Obelisks probably rely on microbial host cells to replicate, including those that live inside humans to replicate. Bacteria or fungi are likely hosts, but it is not known which exact species harbour these elements. </p>
<p>However, the researchers provide a critical lead through the analysis by providing strong evidence that a common bacterial component of dental plaque, <em>Streptococcus sanguinis</em>, plays host to a specific obelisk type.</p>
<figure class="align-center ">
<img alt="Illustration of the human gut full of microbes" src="https://images.theconversation.com/files/573105/original/file-20240202-29-62uqwp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/573105/original/file-20240202-29-62uqwp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/573105/original/file-20240202-29-62uqwp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/573105/original/file-20240202-29-62uqwp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/573105/original/file-20240202-29-62uqwp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=425&fit=crop&dpr=1 754w, https://images.theconversation.com/files/573105/original/file-20240202-29-62uqwp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=425&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/573105/original/file-20240202-29-62uqwp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=425&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">We might have to re-think the gut microbiome.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/3d-rendered-medical-illustration-microbiome-small-2221001821">SciePro/Shutterstock</a></span>
</figcaption>
</figure>
<h2>Friend or foe?</h2>
<p>As <em>S sanguinis</em> is easy to grow and experiment on in the laboratory, this will provide a valuable model for understanding the fundamentals of obelisk biology. </p>
<p>This is critical, as nothing is known about the broader evolutionary and ecological significance of obelisks. They may be parasitic and harm host cells, or they may be beneficial. </p>
<p>Hosts may have evolved elaborate defence mechanisms against obelisks, or else actively recruit them to gain some unsuspected advantage. If obelisks change or upset the human microbiome, this may in turn have implications for human health – they may even have therapeutic potential. </p>
<p>Alternatively, obelisks may cause neither harm nor benefit to their microbial host, or to humans. Instead, they may simply exist as stealthy evolutionary passengers, silently and endlessly replicating, like the original “selfish gene”.</p><img src="https://counter.theconversation.com/content/222296/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ed Feil does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Your mouth and your gut is full of them. But we don’t know if they’re friend or foe.Ed Feil, Professor of Microbial Evolution at The Milner Centre for Evolution, University of BathLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2224462024-02-02T16:38:10Z2024-02-02T16:38:10ZHow long might your dog live? New study calculates life expectancy for different breeds<figure><img src="https://images.theconversation.com/files/572481/original/file-20240131-25-hw9am.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Survival curves for eight pure breeds. Border collie (dark blue), border terrier (light blue), bulldog (green), French bulldog (red), labrador retriever (orange), mastiff (purple), miniature dachshund (pink) and pug (brown). All purebreds vary significantly from crossbreds (light purple). </span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/dog-breeds-whippet-greyhound-hunting-437336992">Liliya Kulianionak/Shutterstock</a></span></figcaption></figure><p>The UK has long been considered to have some of the strongest animal welfare laws in the world. Beginning with <a href="https://edm.parliament.uk/early-day-motion/59989/200th-anniversary-of-the-cruel-treatment-of-cattle-act-1822">Martin’s act</a> on the cruel treatment of cattle, through to the <a href="https://www.legislation.gov.uk/ukpga/2006/45/contents">Animal Welfare Act 2006</a> and then <a href="https://www.parliament.uk/business/news/2019/april/royal-assent-finns-law/">Finn’s law</a> to protect service animals, UK animal welfare laws have sought to reduce harm and cruelty to animals. But what happens when companion animals suffer or live shorter lives simply because of their genetic make-up?</p>
<p>On average, <a href="https://www.rvc.ac.uk/Media/Default/VetCompass/Infograms/220422%20Life%20Tables.pdf">dogs live for 10-13 years</a>, which is considered roughly equivalent to between 60-74 human years.</p>
<p>Small, long-nosed dogs have the highest life expectancies in the UK, while male dogs from medium-sized, flat-faced breeds such as English bulldogs have the lowest, according to a new study published in <a href="https://www.nature.com/articles/s41598-023-50458-w">Scientific Reports</a>. The research team’s results were based on data from more that 580,000 individual dogs from over 150 different breeds and could help identify those dogs most at risk of an early death. </p>
<p>The study is an important one, not least because of its size and scope, but also because very little research of this type had been done previously. We have <a href="https://www.who.int/data/gho/data/themes/mortality-and-global-health-estimates/ghe-life-expectancy-and-healthy-life-expectancy">life expectancy tables</a> and research for humans that show how long we might be expected to live according to a range of factors. But there has been very little research into dog life expectancy that considered how different factors affect lifespan. </p>
<p>The research team created a database of 584,734 dogs using data from 18 different UK sources. These included breed registries, vets, pet insurance companies, animal welfare charities and academic institutions. </p>
<p>Dogs included were from one of 155 pure breeds or classified as a crossbreed, and 284,734 of the dogs had died before being added to the database. Breed, sex, date of birth, and date of death (if applicable) were included for all dogs. </p>
<p>Pure-bred dogs were assigned to size (small, medium or large) and head shape (short-nosed, medium-nosed and long-nosed) categories based on the <a href="https://www.thekennelclub.org.uk/search/breeds-a-to-z/">Kennel Club’s literature</a>. The researchers then calculated median life expectancy for all breeds individually and then for the crossbreed group. Finally, they calculated life expectancy for each combination of sex, size and head shape.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/573116/original/file-20240202-29-nnz0m1.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Line graph showing probability different dog breeds will reach certain ages." src="https://images.theconversation.com/files/573116/original/file-20240202-29-nnz0m1.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/573116/original/file-20240202-29-nnz0m1.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=404&fit=crop&dpr=1 600w, https://images.theconversation.com/files/573116/original/file-20240202-29-nnz0m1.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=404&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/573116/original/file-20240202-29-nnz0m1.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=404&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/573116/original/file-20240202-29-nnz0m1.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=508&fit=crop&dpr=1 754w, https://images.theconversation.com/files/573116/original/file-20240202-29-nnz0m1.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=508&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/573116/original/file-20240202-29-nnz0m1.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=508&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Survival curves for 8 purebreds: Border Collie (dark blue, x̃ = 13.1), Border Terrier (light blue, x̃ = 14.2), Bulldog (green, x̃ = 9.8), French Bulldog (red, x̃ = 9.8), Labrador Retriever (orange, x̃ = 13.1), Mastiff (purple, x̃ = 9.0), Miniature Dachshund (pink, x̃ = 12.2) and Pug (brown, x̃ = 11.6).</span>
<span class="attribution"><a class="source" href="https://www.nature.com/articles/s41598-023-50458-w/figures/3">McMillan, K.M., Bielby, J., Williams, C.L. et al. / Scientific Reports</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<h2>How long do dogs live?</h2>
<p>This study from researchers at the Dogs Trust provides us with new information about the life expectancy of our canine companions. The researchers found that small, long-nosed female dogs tended to have the longest lifespans among pure breeds overall, with a median lifespan of 13.3 years. But breeds with flat-faces had a median lifespan of 11.2 years, and a 40% increased risk of shorter lives than dogs with medium-length snouts, such as spaniels.</p>
<p>Amongst the 12 most popular breeds, which accounted for more than 50% of all recorded pure breeds in the database, labradors had a median life expectancy of 13.1 years, jack russell terriers had a median life expectancy of 13.3 years, and cavalier king charles spaniels had a median life expectancy of 11.8 years. </p>
<p>Pure breeds had a higher median life expectancy than crossbreeds (12.7 years compared to 12.0 years), while female dogs had a slightly higher median life expectancy than males (12.7 years compared to 12.4 years).</p>
<h2>The ethics of ageing</h2>
<p>Research has previously suggested a <a href="https://www.theguardian.com/lifeandstyle/2020/feb/07/popularity-of-pug-flat-nosed-dogs-could-be-fuelling-rise-in-canine-fertility-clinics">growing popularity of small nose dogs</a> such as bulldog breeds and pugs. These dogs have become fashionable and highly prized as pets, but are prone to various health problems, including brachycephalic obstructive airway syndrome (Boas). </p>
<p>This potentially life-threatening condition includes <a href="https://onlinelibrary.wiley.com/doi/full/10.1111/jsap.12286#:%7E:text=The%20brachycephalic%20breeds%20have%20been,nares%20and%20overlong%20soft%20palate.">symptoms</a> such as panting, overheating, exercise intolerance, retching, gastrointestinal signs and disturbed sleep patterns. So for some of these dogs, their life is potentially marked by suffering. This latest study shows they are also likely to live shorter lives. </p>
<p>This raises some questions about dog ownership and the ethics of breeding dogs likely to suffer from Boas. It might be seen as cruel to breed dogs that are either prone to or bound to suffer. </p>
<p>Other countries, including the Netherlands, have considered whether to <a href="https://www.fecava.org/news-and-events/news/dutch-prohibition-of-the-breeding-of-dogs-with-too-short-muzzles/">limit the breeding of these dogs</a> to prevent such suffering and we might expect UK law to consider this. But while the Animal Welfare Act creates an offence of <a href="https://www.legislation.gov.uk/ukpga/2006/45/section/4">causing unnecessary suffering</a>, this relates to suffering of a protected animal that is already alive. </p>
<p>So, the act of breeding an animal with Boas is unlikely to be caught by these provisions and once in ownership of a dog with Boas, the owner has to treat that companion animal in accordance with its normal functions. Even though these conditions may be problematic if they are a natural part of the dog’s make-up, there is no offence of unnecessary suffering simply by having the dog. </p>
<p>The animal welfare acts include a duty to <a href="https://www.legislation.gov.uk/ukpga/2006/45/section/9">provide for good animal welfare</a>. This means that dog owners should understand the needs of their chosen companion animal and should be confident that they can provide for them. </p>
<p>In addition to identifying possible directions for future research and animal welfare interventions, this study provides some important information that might help some potential owners decide which dog is right for them.</p><img src="https://counter.theconversation.com/content/222446/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Angus Nurse has previously received funding from the Department for Environment Food and Rural Affairs to investigate the issue of dangerous dogs and responsible dog ownership.</span></em></p>New research shows that certain breeds tend to live longer than others, and this could help potential owners decide which companion is best for them.Angus Nurse, Professor of Law and Environmental Justice, Anglia Ruskin UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2201342024-01-22T13:32:06Z2024-01-22T13:32:06ZAlcohol and drugs rewire your brain by changing how your genes work – research is investigating how to counteract addiction’s effects<figure><img src="https://images.theconversation.com/files/569941/original/file-20240117-21-ycbpim.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C3600%2C1810&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Alcohol and other drugs can overpower the reward pathways of the brain.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/illustration-of-a-brain-cocktail-isolate-don-a-royalty-free-image/1263367270">Simona Dumitru/Moment via Getty Images</a></span></figcaption></figure><p>Many people are wired to <a href="https://www.penguinrandomhouse.ca/books/306396/the-compass-of-pleasure-by-david-j-linden/9780143120759">seek and respond to rewards</a>. Your brain interprets food as rewarding when you are hungry and water as rewarding when you are thirsty. But addictive substances like alcohol and drugs of abuse can <a href="https://doi.org/10.1016/S2215-0366(16)00104-8">overwhelm the natural reward pathways</a> in your brain, resulting in intolerable cravings and reduced impulse control. </p>
<p>A popular misconception is that addiction is a result of low willpower. But an explosion of knowledge and technology in the field of <a href="https://plato.stanford.edu/entries/molecular-genetics/">molecular genetics</a> has changed our basic understanding of addiction drastically over the past decade. The general consensus among scientists and health care professionals is that there is a <a href="https://www.penguinrandomhouse.ca/books/557515/never-enough-by-judith-grisel/9780525434900">strong neurobiological and genetic basis</a> for addiction.</p>
<p>As a <a href="https://scholar.google.com/citations?user=XgunjGkAAAAJ&hl=en">behavioral neurogeneticist</a> <a href="https://www.kaunlab.com">leading a team</a> investigating the molecular mechanisms of addiction, I combine neuroscience with genetics to understand how alcohol and drugs influence the brain. In the past decade, I have seen changes in our understanding of the molecular mechanisms of addiction, largely due to a better understanding of how genes are dynamically regulated in the brain. New ways of thinking about how addictions form have the potential to change how we approach treatment.</p>
<h2>Alcohol and drugs affect brain gene activity</h2>
<p>Each of your brain cells has your genetic code stored in long strands of DNA. For all that DNA to fit into a cell, it needs to be packed tightly. This is achieved by winding the DNA around “spools” of protein <a href="https://www.genome.gov/genetics-glossary/histone">called histones</a>. Areas where DNA is unwound contain active genes coding for proteins that serve important functions within the cell.</p>
<p>When gene activity changes, the proteins your cells produce also change. Such changes can range from a single neuronal connection in your brain to how you behave. This genetic choreography suggests that while your genes affect how your brain develops, <a href="https://theconversation.com/brains-work-via-their-genes-just-as-much-as-their-neurons-47522">which genes are turned on or off</a> when you are learning new things is dynamic and adapts to suit your daily needs.</p>
<p>Recent data from animal models suggests that alcohol and drugs of abuse directly influence <a href="https://doi.org/10.1523/JNEUROSCI.1649-20.2020">changes in gene expression</a> in areas of the brain that help drive memory and reward responses. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/567627/original/file-20240103-29-mcair4.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram magnifying the nucleus of a neuron, showing spirals of DNA wound around bundles of protein" src="https://images.theconversation.com/files/567627/original/file-20240103-29-mcair4.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/567627/original/file-20240103-29-mcair4.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=358&fit=crop&dpr=1 600w, https://images.theconversation.com/files/567627/original/file-20240103-29-mcair4.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=358&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/567627/original/file-20240103-29-mcair4.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=358&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/567627/original/file-20240103-29-mcair4.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=449&fit=crop&dpr=1 754w, https://images.theconversation.com/files/567627/original/file-20240103-29-mcair4.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=449&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/567627/original/file-20240103-29-mcair4.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=449&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Within each neuron in the brain, how tightly DNA is wound around or bound to histones and other proteins determines which genes are expressed and which proteins are produced.</span>
<span class="attribution"><span class="source">Karla Kaun and Vinald Francis</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>There are <a href="https://doi.org/10.1523/JNEUROSCI.1649-20.2020">many ways</a> addictive substances can change gene expression. They can alter which proteins bind to DNA to turn genes on and off and which segments of DNA are unwound. They can change the process of how DNA is read and translated into proteins, as well as alter the proteins that determine how cells use energy to function.</p>
<p>For example, alcohol can cause an alternative form of a gene to be expressed in the memory circuits <a href="https://doi.org/10.1534/genetics.120.303101">in flies</a> <a href="https://doi.org/10.1038/s41598-023-30926-z">and people</a>, resulting in changes in dopamine receptors and transcription factors involved in reward signaling and neuronal function. Similarly, cocaine can cause an alternative form of a gene to be expressed in the <a href="https://doi.org/10.1016/j.neuron.2021.08.008">reward centers</a> <a href="https://doi.org/10.1016/j.biopsych.2017.11.027">of mice</a>, leading them to seek out more cocaine.</p>
<p>Exactly how these drugs cause changes in gene regulation is unknown. However, a direct link between alcohol consumption and changes in gene expression in mice provides a clue. A byproduct of alcohol being broken down in the liver called acetate can cross the blood-brain barrier and <a href="https://doi.org/10.1038/s41586-019-1700-7">unwind DNA from histones</a> in mouse memory circuits. </p>
<p>Alcohol, nicotine, cocaine and opioids also all activate important signaling pathways that are <a href="https://doi.org/10.1111/jnc.12725">central regulators of metabolism</a>. This suggests they can also affect many aspects of neuronal function and consequently affect which genes are expressed.</p>
<h2>Changing brain gene activity with lifestyle</h2>
<p>How addictive substances change cell function is complex. The version of a gene you’re born with can be modified in many ways before it becomes a functional protein, including exposure to alcohol and drugs. Rather than discouraging researchers, this complexity is empowering because it provides evidence that changes to gene expression in your brain aren’t permanent. They can also be altered by medications and lifestyle choices.</p>
<p>Many commonly prescribed medications for mental health disorders also affect gene expression. <a href="https://doi.org/10.1038%2Fs41398-019-0589-0">Antidepressants and</a> <a href="https://doi.org/10.1016/j.jpsychires.2013.05.028">mood stabilizers</a> can change how DNA is modified and which genes are expressed. For example, a commonly prescribed drug for depression called escitalopram affects how tightly wound DNA is and can change the expression of genes important to brain plasticity.</p>
<p>Additionally, <a href="https://theconversation.com/customizing-mrna-is-easy-and-thats-what-makes-it-the-next-frontier-for-personalized-medicine-a-molecular-biologist-explains-216127">mRNA-based therapies</a> can specifically change which genes are expressed to treat diseases like cancer. In the future, we may discover similar therapies for alcohol and substance use disorder. These treatments could potentially target important <a href="https://doi.org/10.1016%2Fj.tins.2021.09.006">signaling pathways linked to addiction</a>, altering how brain circuits function and how alcohol and drugs affect them.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/569945/original/file-20240117-29-n459lb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Close-up of person sitting with crossed legs on a yoga mat, hands resting on knees with pointer finger touching thumb" src="https://images.theconversation.com/files/569945/original/file-20240117-29-n459lb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/569945/original/file-20240117-29-n459lb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/569945/original/file-20240117-29-n459lb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/569945/original/file-20240117-29-n459lb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/569945/original/file-20240117-29-n459lb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/569945/original/file-20240117-29-n459lb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/569945/original/file-20240117-29-n459lb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Exercise and other lifestyle choices can affect gene regulation.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/indonesian-woman-is-meditating-in-a-half-lotus-royalty-free-image/1391023941?adppopup=true">Afriandi/Moment via Getty Images</a></span>
</figcaption>
</figure>
<p>Lifestyle choices can also affect gene expression in your brain, though researchers don’t yet know whether they can alter the changes induced by addictive substances. </p>
<p>Like alcohol and drugs, <a href="https://theconversation.com/what-you-eat-can-reprogram-your-genes-an-expert-explains-the-emerging-science-of-nutrigenomics-165867">dietary changes</a> can affect gene expression in many ways. In flies, a high sugar diet can <a href="https://doi.org/10.1126/sciadv.abc8492">reprogram the ability to taste sweetness</a> by tapping into a gene expression network involved in development.</p>
<p><a href="https://doi.org/10.1016/j.cpnec.2022.100152">Intensive</a> <a href="https://doi.org/10.1016/j.psyneuen.2013.11.004">meditation</a>, even after only <a href="https://doi.org/10.1016/j.bbi.2019.11.003">one day</a>, can also affect gene regulation in your brain through similar mechanisms. Attending a <a href="https://doi.org/10.1016/j.cpnec.2022.100152">monthlong meditation retreat</a> reduces the expression of genes that affect inflammation, and experienced meditators can reduce inflammatory genes after just <a href="https://doi.org/10.1016/j.bbi.2019.11.003">one day of intensive meditation</a>. </p>
<p>Work in animal models has also shown that exercise changes gene expression by altering both <a href="https://doi.org/10.1016/j.brainres.2020.147191">histones</a> <a href="https://doi.org/10.1016/j.molmet.2021.101398">and the</a> <a href="https://doi.org/10.1111/j.1460-9568.2010.07508.x">molecular tags</a> directly attached to DNA. This increases the activity of genes important to the activity and plasticity of neurons, supporting the idea that <a href="https://theconversation.com/high-intensity-exercise-improves-memory-and-wards-off-dementia-127001">exercise improves learning and memory</a> and can decrease the risk of dementia.</p>
<p>From <a href="https://doi.org/10.1037/hea0000297">Dry January</a> and beyond, many factors can have profound effects on your brain biology. Taking steps to reduce consumption of alcohol and drugs and picking up healthy lifestyle practices can help stabilize and bring long-lasting benefits for your physical and mental health.</p><img src="https://counter.theconversation.com/content/220134/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Karla Kaun receives funding from the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse and the National Institute of General Medical Sciences.</span></em></p>Improved understanding of the molecular mechanisms of addiction can change how researchers and clinicians approach treatments.Karla Kaun, Associate Professor of Neuroscience, Brown UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2113962023-11-29T13:38:49Z2023-11-29T13:38:49ZMicroRNA is the master regulator of the genome − researchers are learning how to treat disease by harnessing the way it controls genes<figure><img src="https://images.theconversation.com/files/561973/original/file-20231127-27-vqtw0l.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2121%2C1400&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">RNA is more than just a transitional state between DNA and protein.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/molecule-of-mrna-illustration-royalty-free-illustration/1450368774">Kateryna Kon/Science Photo Library via Getty Images</a></span></figcaption></figure><p>The Earth <a href="https://www.scientificamerican.com/article/evolution-of-earth/">formed 4.5 billion years ago</a>, and life less than a billion years after that. Although life as we know it is <a href="https://sciencing.com/abundant-organic-compound-earth-22851.html">dependent on four major macromolecules</a> – DNA, RNA, proteins and lipids – only one is thought to have been present at the beginning of life: RNA. </p>
<p>It is no surprise that <a href="https://www.khanacademy.org/science/ap-biology/natural-selection/origins-of-life-on-earth/a/rna-world">RNA likely came first</a>. It is the only one of those major macromolecules that can both replicate itself and catalyze chemical reactions, both of which are essential for life. Like DNA, RNA is made from individual nucleotides linked into chains. Scientists initially understood that genetic information flows in one direction: DNA is transcribed into RNA, and RNA is translated into proteins. That principle is called the <a href="https://www.genome.gov/genetics-glossary/Central-Dogma">central dogma of molecular biology</a>. But there are many deviations.</p>
<p>One major example of an exception to the central dogma is that some RNAs are never translated or coded into proteins. This fascinating diversion from the central dogma is what led me to <a href="https://scholar.google.com/citations?user=4JMQMLgAAAAJ&hl=en">dedicate my scientific career</a> to understanding how it works. Indeed, research on RNA has lagged behind the other macromolecules. Although there are multiple classes of these so-called noncoding RNAs, researchers like myself have started to focus a great deal of attention on short stretches of genetic material called <a href="https://www.ibiology.org/genetics-and-gene-regulation/introduction-to-micrornas/">microRNAs</a> and their potential to treat various diseases, including cancer.</p>
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<figcaption><span class="caption">MicroRNAs play a key role in regulating gene expression.</span></figcaption>
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<h2>MicroRNAs and disease</h2>
<p>Scientists regard microRNAs as <a href="https://doi.org/10.1146/annurev-pharmtox-010510-100517">master regulators of the genome</a> due to their ability to bind to and alter the expression of many protein-coding RNAs. Indeed, a single microRNA can regulate anywhere from 10 to 100 protein-coding RNAs. Rather than translating DNA to proteins, they instead can bind to protein-coding RNAs to silence genes. </p>
<p>The reason microRNAs can regulate such a diverse pool of RNAs stems from their ability to bind to target RNAs they don’t perfectly match up with. This means a single microRNA can often regulate a pool of targets that are all involved in similar processes in the cell, leading to an enhanced response.</p>
<p>Because a single microRNA can regulate multiple genes, many microRNAs can contribute to disease when they become dysfunctional.</p>
<p>In 2002, researchers first identified the role dysfunctional microRNAs play in disease through patients with a type of blood and bone marrow cancer called <a href="https://doi.org/10.1073/pnas.242606799">chronic lymphocytic leukemia</a>. This cancer results from the <a href="https://doi.org/10.1038/cdd.2009.69">loss of two microRNAs</a> normally involved in blocking tumor cell growth. Since then, scientists have identified <a href="https://mirbase.org/browse/results/?organism=hsa">over 2,000 microRNAs in people</a>, many of which are altered in various diseases. </p>
<p>The field has also developed a fairly solid understanding of how microRNA dysfunction contributes to disease. Changing one microRNA can change several other genes, resulting in a plethora of alterations that can collectively reshape the cell’s physiology. For example, over half of all cancers have significantly reduced activity in a <a href="https://doi.org/10.3389/fcell.2021.640587">microRNA called miR-34a</a>. Because miR-34a regulates many genes involved in preventing the growth and migration of cancer cells, losing miR-34a can increase the risk of developing cancer.</p>
<p>Researchers are looking into using microRNAs as therapeutics for cancer, heart disease, neurodegenerative disease and others. While results in the laboratory have been promising, bringing microRNA treatments into the clinic has <a href="https://doi.org/10.1016/j.tig.2022.02.006">met multiple challenges</a>. Many are related to inefficient delivery into target cells and poor stability, which limit their effectiveness.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/561975/original/file-20231127-26-jqjjuh.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram showing a loop of microRNA binding to a strand of mRNA as it's being translated from DNA" src="https://images.theconversation.com/files/561975/original/file-20231127-26-jqjjuh.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/561975/original/file-20231127-26-jqjjuh.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=385&fit=crop&dpr=1 600w, https://images.theconversation.com/files/561975/original/file-20231127-26-jqjjuh.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=385&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/561975/original/file-20231127-26-jqjjuh.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=385&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/561975/original/file-20231127-26-jqjjuh.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=484&fit=crop&dpr=1 754w, https://images.theconversation.com/files/561975/original/file-20231127-26-jqjjuh.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=484&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/561975/original/file-20231127-26-jqjjuh.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=484&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">MicroRNA can silence genes by binding to mRNA.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Conceptual_overview_of_multiomics_-_digital_skewed.png">Kajsa Mollersen/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<h2>Delivering microRNA to cells</h2>
<p>One reason why delivering microRNA treatments into cells is difficult is because microRNA treatments need to be delivered specifically to diseased cells while avoiding healthy cells. Unlike <a href="https://theconversation.com/how-mrna-and-dna-vaccines-could-soon-treat-cancers-hiv-autoimmune-disorders-and-genetic-diseases-170772">mRNA COVID-19 vaccines</a> that are taken up by scavenging immune cells whose job is to detect foreign materials, microRNA treatments need to fool the body into thinking they aren’t foreign in order to avoid immune attack and get to their intended cells.</p>
<p>Scientists are studying various ways to deliver microRNA treatments to their specific target cells. One method garnering a great deal of attention relies on directly <a href="https://doi.org/10.1093/narcan/zcab030">linking the microRNA to a ligand</a>, a kind of small molecule that binds to specific proteins on the surface of cells. Compared with healthy cells, diseased cells can have a disproportionate number of some surface proteins, or receptors. So, ligands can help microRNAs home specifically to diseased cells while avoiding healthy cells. The first ligand approved by the U.S. Food and Drug Administration to deliver small RNAs like microRNAs, <a href="https://doi.org/10.1007/s40265-020-01269-0">N-acetylgalactosamine, or GalNAc</a>, preferentially delivers RNAs to liver cells.</p>
<p>Identifying ligands that can deliver small RNAs to other cells requires finding receptors expressed at high enough levels on the surface of target cells. Typically, <a href="https://doi.org/10.1038/nrd4519">over one million copies per cell</a> are needed in order to achieve sufficient delivery of the drug.</p>
<p>One ligand that stands out is <a href="https://theconversation.com/adding-folic-acid-to-staple-foods-can-prevent-birth-defects-but-most-countries-dont-do-it-55533">folate, also referred to as vitamin B9</a>, a small molecule critical during periods of rapid cell growth such as fetal development. Because some tumor cells have over one million folate receptors, this ligand provides sufficient opportunity to deliver enough of a therapeutic RNA to target different types of cancer. For example, my laboratory developed a new molecule <a href="https://doi.org/10.1126/scitranslmed.aam9327">called FolamiR-34a</a> – folate linked to miR-34a – that reduced the size of breast and lung cancer tumors in mice.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/561976/original/file-20231127-18-5pbfrd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Microscopy image juxtaposing endothelial cells sprouting extensions to form new blood vessels and a cell bathed in microRNA unable to sprout" src="https://images.theconversation.com/files/561976/original/file-20231127-18-5pbfrd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/561976/original/file-20231127-18-5pbfrd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=387&fit=crop&dpr=1 600w, https://images.theconversation.com/files/561976/original/file-20231127-18-5pbfrd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=387&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/561976/original/file-20231127-18-5pbfrd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=387&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/561976/original/file-20231127-18-5pbfrd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=486&fit=crop&dpr=1 754w, https://images.theconversation.com/files/561976/original/file-20231127-18-5pbfrd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=486&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/561976/original/file-20231127-18-5pbfrd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=486&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Tumors can exploit healthy cells to grow blood vessels that provide them nutrients, as seen in the endothelial cells to the left sprouting extensions. Exposing these cells to certain microRNAs, however, can disable that growth, as seen in the cell to the right.</span>
<span class="attribution"><a class="source" href="https://flic.kr/p/2hrJ3g4">Dudley Lab, University of Virginia School of Medicine/NIH via Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
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<h2>Making microRNAs more stable</h2>
<p>One of the other challenges with using small RNAs is their <a href="https://doi.org/10.1093/narcan/zcab030">poor stability</a>, which leads to their rapid degradation. As such, RNA-based treatments are generally short-lived in the body and require frequent doses to maintain a therapeutic effect. </p>
<p>To overcome this challenge, researchers are <a href="https://doi.org/10.1093/narcan/zcab030">modifying small RNAs</a> in various ways. While each RNA requires a specific modification pattern, successful changes can <a href="https://doi.org/10.1038/s41388-023-02801-8">significantly increase their stability</a>. This reduces the need for frequent dosing, subsequently decreasing treatment burden and cost. </p>
<p>For example, <a href="https://doi.org/10.1089%2Fnat.2018.0736">modified GalNAc-siRNAs</a>, another form of small RNAs, reduces dosing from every few days to once every six months in nondividing cells. My team developed <a href="https://doi.org/10.1038/s41388-023-02801-8">folate ligands</a> linked to modified microRNAs for cancer treatment that reduced dosing from once every other day to once a week. For diseases like cancer where cells are rapidly dividing and quickly diluting the delivered microRNA, this increase in activity is a significant advancement in the field. We anticipate this accomplishment will facilitate further development of this folate-linked microRNA as a cancer treatment in the years to come.</p>
<p>While there is still considerable work to be done to overcome the hurdles associated with microRNA treatments, it’s clear that RNA shows promise as a therapeutic for many diseases.</p><img src="https://counter.theconversation.com/content/211396/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Andrea Kasinski receives funding from the National Institutes of Health, Department of Defense, and the American Lung Association. Kasinski is also the inventor on multiple patients associated with her discoveries in the RNA therapeutics field. </span></em></p>When just one of the thousands of microRNAs in people go awry, it can cause diseases ranging from heart disease to cancer.Andrea Kasinski, Associate Professor of Biological Sciences, Purdue UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2093122023-09-15T12:31:41Z2023-09-15T12:31:41ZCan at-home DNA tests predict how you’ll respond to your medications? Pharmacists explain the risks and benefits of pharmacogenetic testing<figure><img src="https://images.theconversation.com/files/545852/original/file-20230831-15-xftd5k.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2070%2C1449&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Pharmacogenetic testing is a form of precision medicine, using your genes to personalize your care.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/medicine-concept-royalty-free-image/815702424">D3Damon/E+ via Getty Images</a></span></figcaption></figure><p>Have you ever wondered why certain medications <a href="https://theconversation.com/why-prescription-drugs-can-work-differently-for-different-people-168645">don’t seem to work as well</a> for you as they do for others? This variability in drug response is what pharmacogenomic testing hopes to explain by looking at the genes within your DNA. </p>
<p><a href="https://www.cdc.gov/genomics/disease/pharma.htm">Pharmacogenomics, or PGx</a>, is the study of how genes affect your response to medications. <a href="https://www.genome.gov/genetics-glossary/Gene">Genes are segments of DNA</a> that serve as an instruction manual for cells to make proteins. Some of these proteins break down or transport certain medications through the body. Others are proteins that medications target to generate a desired effect.</p>
<p><a href="https://www.pharmacy.pitt.edu/people/kayla-rowe">As pharmacists</a> <a href="https://scholar.google.com/citations?user=9Np7_DYAAAAJ&hl=en">who see</a> <a href="https://scholar.google.com/citations?user=LKG31OkAAAAJ&hl=en">patients who</a> have stopped multiple medications because of side effects or ineffectiveness, we believe pharmacogenomic testing has the potential to help guide health care professionals to more precise dosing and prescribing.</p>
<h2>How do PGx tests work?</h2>
<p><a href="https://medlineplus.gov/lab-tests/pharmacogenetic-tests/">PGx tests</a> look for variations within the genes of your DNA to predict drug response. For instance, the presence of one genetic variant might predict that the specific protein it codes for is unable to break down a particular medication. This could potentially lead to increased drug levels in your body and an increased risk of side effects. The presence of another genetic variant might predict the opposite: It might predict that the protein it codes for is breaking down a medication more rapidly than expected, which may decrease the drug’s effectiveness.</p>
<p>For example, <a href="https://doi.org/10.1002/cpt.2903">citalopram is an antidepressant</a> broken down by a protein called CYP2C19. Patients with genetic variants that code for a version of this protein with a reduced ability to break down the drug may have an increased risk of side effects.</p>
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<figcaption><span class="caption">PGx is a form of personalized or precision medicine.</span></figcaption>
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<p>Currently, there are over 80 medications with <a href="https://cpicpgx.org/">prescribing recommendations</a> based on PGx results, including treatments for depression, cancer and heart disease. There are commercially available PGx tests that patients can have sent directly to their doorstep with or without the involvement of a health care professional. These direct-to-consumer PGx tests collect DNA from either a saliva sample or cheek swab that is then sent to the laboratory. Results can take anywhere from a few days to a few weeks depending on the company. </p>
<p>Some companies <a href="https://doi.org/10.1038%2Fnature15817">require a consultation</a> with a health care provider, often a pharmacist or genetic counselor, who can facilitate a test order and discuss any medication changes once the results come back. </p>
<h2>Limitations of PGx testing</h2>
<p>PGx testing will not be able to predict how you will respond to all medications for several reasons.</p>
<p>First, most PGx tests <a href="https://doi.org/10.3390/genes11121456">do not look for every possible variant</a> of every gene in the human genome. Instead, they look only at a limited number of genes and variants strongly linked to specific drugs. PGx tests can predict how you will respond only to medications associated with the genes it tests for. </p>
<p>Some drugs are broken down in very complicated pathways entailing multiple proteins and byproducts, and the usefulness of PGx testing for them remains unclear. For example, the <a href="https://www.pharmgkb.org/pathway/PA166170276">antidepressant bupropion</a> has three major pathways involved in its breakdown and forms three active byproducts that can interact with other drugs or body processes. This makes predicting how you will respond to the drug much more challenging because there is more than one variable involved. In many cases, there also isn’t conclusive data to confidently predict the general function of a protein and how it would affect your response to a drug.</p>
<p>The applicability of PGx test results is additionally limited by a <a href="https://theconversation.com/uncovering-the-genetic-basis-of-mental-illness-requires-data-and-tools-that-arent-just-based-on-white-people-this-international-team-is-collecting-dna-samples-around-the-globe-185997">lack of diversity of study participants</a>. Typically, populations of European ancestry are overrepresented in clinical trials. An ongoing research initiative by the National Institutes of Health called the <a href="https://allofus.nih.gov/">All of Us Research Program</a> aims to address this issue by collecting genetic samples from people of diverse backgrounds. </p>
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<figcaption><span class="caption">The All of Us research program seeks to conduct research that is more representative of a diverse population.</span></figcaption>
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<p>Another limitation of direct-to-consumer PGx tests is that they can predict drug response based only on your genetics. <a href="https://my.clevelandclinic.org/health/diagnostics/21093-pharmacogenomics">Lifestyle and environmental factors</a> such as your age, liver or kidney function, tobacco use, drug interactions and other diseases can heavily influence how you may respond to medication. For example, leafy greens with high amounts of vitamin K can <a href="https://www.pennmedicine.org/updates/blogs/heart-and-vascular-blog/2015/june/consistency-not-avoidance-the-truth-about-blood-thinners-leafy-greens-and-vitamin-k">lower the effectiveness</a> of the blood thinner warfarin. But PGx tests don’t take these factors into account.</p>
<p>Finally, your PGx results may predict that you may respond to medications differently, but this does not guarantee that the medication won’t have its intended effect. In other words, PGx testing is predictive rather than deterministic.</p>
<h2>Risks of PGx testing</h2>
<p>PGx testing carries the risk of not telling the whole story of drug response. If variations within the gene are not found, the testing company often assumes the proteins those genes code for function normally. Because of this assumption, someone carrying a rare or unknown variant may receive inaccurate results.</p>
<p>It may be tempting for some people to see their results and want to change their dose or discontinue their medications. However, this can be dangerous. Abruptly stopping some medications may cause withdrawal effects. Never change the way you take your medications without consulting your pharmacist and physician first.</p>
<p>Sharing your PGx test results with all the clinicians involved in your care can help prevent medication failure and improve safety. Pharmacists are increasingly trained in pharmacogenomics and can serve as a resource to address medication-related questions or concerns.</p>
<p>PGx tests that are not authorized by the Food and Drug Administration cannot be clinically interpreted and therefore cannot be used to inform prescribing. Results from these tests should not be added to your medical record.</p>
<h2>Benefits of PGx testing</h2>
<p>Direct-to-consumer PGx testing can empower patients to advocate for themselves and be an active participant in their health care by increasing access to and knowledge of their genetic information.</p>
<p>Patients’ knowledge of their PGx genetic profile has the potential to improve treatment safety. For example, a 2023 study of over 6,000 patients in Europe found that those who used their PGx results to guide medication therapy were <a href="https://doi.org/10.1016/s0140-6736(22)01841-4">30% less likely</a> to experience adverse drug reactions.</p>
<p>Most PGx test results stay valid throughout a patient’s life, and <a href="https://mhealthfairview.org/services/pharmacogenomics">retesting is not needed</a> unless additional genes or variants need to be evaluated. As more research on gene variants is conducted, prescribing recommendations may be updated. </p>
<p>Overall, genetic information from direct-to-consumer PGx tests can help you collaborate with health care professionals to select more effective medications with a lower risk of side effects.</p><img src="https://counter.theconversation.com/content/209312/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Genetic testing can help take the guesswork out of finding the right treatment. For certain diseases. To an extent.Kayla B. Rowe, Fellow in Clinical Pharmacogenomics, University of PittsburghLucas A. Berenbrok, Associate Professor of Pharmacy and Therapeutics, University of PittsburghPhilip Empey, Associate Professor of Pharmacogenomics, University of PittsburghLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2121832023-09-07T07:15:46Z2023-09-07T07:15:46ZLife insurers can charge more or decline cover based on your genetic test results. New laws must change this<figure><img src="https://images.theconversation.com/files/546781/original/file-20230907-25-43r0xc.jpg?ixlib=rb-1.1.0&rect=9%2C133%2C6361%2C4107&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/head-shot-stressed-young-woman-holding-1667439796">Shutterstock</a></span></figcaption></figure><p>Genetic tests can provide life-saving information. They can help diagnose disease, enable access to preventive care, prompt early screening and treatment, and guide patients’ therapeutic options. </p>
<p>In Australia, life insurance companies can legally use the results of genetic tests to discriminate. They can decline to provide life insurance coverage, increase the cost of premiums, or place exclusions on an individual’s cover. This is known as “genetic discrimination”.</p>
<p>This week, a number of <a href="https://www.aph.gov.au/News_and_Events/Watch_Read_Listen/ParlView/video/1695787">federal parliamentarians argued for a ban</a> on genetic discrimination by life insurance companies. This follows <a href="https://doi.org/10.26180/23564538">recommendations</a> from our research team for <a href="https://www.mja.com.au/journal/2021/214/4/monitoring-genetic-testing-and-life-insurance-moratorium-australia-national">legislative reform</a> so Australians don’t forego important genetic tests for fear of this discrimination. </p>
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<a href="https://theconversation.com/australians-need-more-protection-against-genetic-discrimination-health-experts-168563">Australians need more protection against genetic discrimination: health experts</a>
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<h2>Why would you have a genetic test?</h2>
<p>We don’t choose our genetic risk factors. They exist from birth, can’t be changed, and are often passed down from parents to children, causing generations of disease. </p>
<p>Genetic testing can, in some cases, stop the generational curse of genetic disease through prevention and early intervention. </p>
<p>One of the most well-known examples is testing for changes in the BRCA1 gene – which significantly increases risks of breast, ovarian and prostate cancer. </p>
<p><a href="https://www.nytimes.com/2015/03/24/opinion/angelina-jolie-pitt-diary-of-a-surgery.html">Angelina Jolie</a>, who carries the BRCA1 gene mutation, famously wrote in the New York Times in 2013 about her decision to have surgeries to drastically reduce her chance of developing cancer. </p>
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<h2>How is this discrimination currently allowed?</h2>
<p>The Disability Discrimination Act 1992 (Cth) prohibits discrimination on a number of different bases, including genetic risk factors. </p>
<p>However, there is a specific carve-out in the Act that allows life insurers to discriminate in ways other entities are prohibited from doing. </p>
<p>This means companies providing insurance for death, income protection, and disability can discriminate on the basis of genetic risk of disease. Other companies that provide risk-rated insurance (where insurers assess an individual’s risk factors and change coverage or premiums based on this risk) can also use genetic test results to discriminate. This includes travel insurance. </p>
<p>Health insurance, however, is not risk-rated. This means a health insurer is not allowed to decline cover or change the cost of premiums based on any risk factors, including genetic risk factors. </p>
<h2>Protections are needed</h2>
<p>Fears of insurance discrimination <a href="https://pubmed.ncbi.nlm.nih.gov/28197815/">deter many people</a> from having genetic testing or participating in genetic research. For this reason, numerous other countries <a href="https://www.genevaassociation.org/sites/default/files/ga2017_globalageing_genetics_and_life_insurance_0.pdf">have banned</a> the use of genetic results by insurance companies. </p>
<p>Canada did so in 2017. Its Act prohibits entities (including insurance companies) from collecting or using genetic results to discriminate against individuals. </p>
<figure class="align-center ">
<img alt="Man has blood taken" src="https://images.theconversation.com/files/546784/original/file-20230907-29-xup8ya.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/546784/original/file-20230907-29-xup8ya.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/546784/original/file-20230907-29-xup8ya.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/546784/original/file-20230907-29-xup8ya.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/546784/original/file-20230907-29-xup8ya.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/546784/original/file-20230907-29-xup8ya.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/546784/original/file-20230907-29-xup8ya.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Canadian insurer’s have been prohibited from genetic discrimination since 2017.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/man-woman-wearing-doctor-uniform-having-2266894075">Shutterstock</a></span>
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<p>Insurance industry bodies frequently raise claims that banning the use of genetic results will increase the cost of premiums, making them unaffordable. </p>
<p>Before the Canadian Act was introduced, its Privacy Commissioner commissioned an <a href="https://www.priv.gc.ca/en/opc-actions-and-decisions/research/explore-privacy-research/2011/gi_macdonald_201107/">actuarial expert</a> and <a href="https://theconversation.com/why-insurers-are-wrong-about-canadas-genetic-non-discrimination-law-81380">economic analyst</a> to consider what impact this ban might have on the Canadian insurance industry. </p>
<p>Both experts concluded the impact of Canada’s ban would be negligible in the medium term, and the Privacy Commissioner <a href="https://www.priv.gc.ca/en/opc-news/news-and-announcements/2017/nr-c_170505/">welcomed the Act</a> as an “important step for privacy and human rights”.</p>
<h2>Genetic testing is likely to expand</h2>
<p>At the moment, only people with a strong personal or family history of certain diseases are eligible for publicly funded genetic testing. </p>
<p>However, research projects such as the <a href="https://dnascreen.monash.edu/">DNA Screen study</a> are piloting <a href="https://www.abc.net.au/radionational/programs/bigideas/dna-screen-testing-disease-cancer-young-population-health/102598372">the offer of</a> DNA screening to the whole population.</p>
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Read more:
<a href="https://theconversation.com/should-i-get-my-dna-tested-we-asked-five-experts-120664">Should I get my DNA tested? We asked five experts</a>
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<p>DNA Screen is offering testing to 10,000 young Australians (18-40 year olds) for genetic risk factors for cancer and heart disease, which can be prevented or treated early. </p>
<p>However, we have to tell people when they sign up about potential life insurance discrimination, and many of them change their minds about being part of our study. </p>
<p>As genetic testing offers may expand to the whole population in the future, every person being offered genetic testing will have to consider the implications for their life insurance. </p>
<h2>The long road to legislating protections</h2>
<p>Following <a href="https://www.aph.gov.au/Parliamentary_Business/Committees/Joint/Corporations_and_Financial_Services/LifeInsurance/Report">parliamentary recommendations</a> to ban the use of genetic results by life insurers in 2018, the life insurance industry <a href="https://www.fsc.org.au/resources-category/standard/1779-standard-11-moratorium-on-genetic-tests-in-life-insurance/file">introduced</a> a partial, self-regulated moratorium on using genetic results in 2019. </p>
<p>We had concerns about its terms and the fact that it was self-regulated, with no government oversight. So we <a href="https://www.monash.edu/medicine/a-glimmer/home">gathered views</a> from <a href="https://pubmed.ncbi.nlm.nih.gov/34544841/">health professionals</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/37169978/">consumers</a>, researchers and <a href="https://pubmed.ncbi.nlm.nih.gov/37573782/">financial advisers</a>. </p>
<p>We found the the industry moratorium <a href="https://pubmed.ncbi.nlm.nih.gov/36509687/">did not meet</a> the expectations of the parliamentary recommendations. Overwhelmingly, patients, the general public, health professionals and genetic researchers believed legislation on this issue was required. Our <a href="https://doi.org/10.26180/23564538">final report</a>, released in June, recommends the Australian government introduce a legislative prohibition on the use of genetic test results in insurance underwriting. </p>
<p>This week, federal MP Josh Burns, Chair of the Parliamentary Joint Committee on Human Rights, took the first step by <a href="https://www.aph.gov.au/News_and_Events/Watch_Read_Listen/ParlView/video/1680734">introducing a motion</a>, for the parliament to consider policy reform on this issue. </p>
<p>This was supported by five other federal MPs, including from the coalition and independents. As Labor MP Louise Miller-Frost explained:</p>
<blockquote>
<p>Australians should be able to make these decisions based on their health needs, not financial ones, and we have the opportunity to make that a reality… self-regulation is clearly not sufficient to protect our interests. I believe legislation is required. </p>
</blockquote>
<p>Separate speeches by MP Dr <a href="https://www.linkedin.com/feed/update/urn:li:activity:7104284518328516608/">Daniel Mulino</a> and Assistant Minister for Health and Ageing <a href="https://www.aph.gov.au/News_and_Events/Watch_Read_Listen/ParlView/video/1695787">Ged Kearney</a> this week also supported the motion. </p>
<p>Ms Kearney spoke about several constituents who have shared their concerns about this issue, and also called for <a href="https://www.aph.gov.au/News_and_Events/Watch_Read_Listen/ParlView/video/1695787">policy changes</a>. She noted the benefits for life insurance companies if people can get genetic testing and are able to take preventive action, to become “better risks”. </p>
<p>The Treasury Department, and Stephen Jones MP (Assistant Treasurer and Financial Services Minister) are now considering the appropriate policy solution, together with the Department of Health and Ageing and the Attorney-General’s Department. There is no timeline for this legislation to be introduced, but this urgent policy change must be prioritised by the current government. </p>
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Read more:
<a href="https://theconversation.com/population-dna-testing-for-disease-risk-is-coming-here-are-five-things-to-know-112522">Population DNA testing for disease risk is coming. Here are five things to know</a>
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<img src="https://counter.theconversation.com/content/212183/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jane Tiller received funding from the Commonwealth Government's Genomic Health Futures Fund to complete this research</span></em></p><p class="fine-print"><em><span>Paul Lacaze received funding from the Commonwealth Government's Genomic Health Futures Fund to complete this research.</span></em></p>Life insurance companies can legally use the results of genetic tests to decline coverage or increase premiums. MPs have called for legislation that bans this practice.Jane Tiller, Ethical, Legal & Social Adviser - Public Health Genomics, Monash UniversityPaul Lacaze, Head, Public Health Genomics Program, Monash UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2120732023-08-27T13:32:44Z2023-08-27T13:32:44ZLearning from failures: Support for scientific research needs to include when things don’t work out<figure><img src="https://images.theconversation.com/files/544660/original/file-20230824-17-fr9wys.jpg?ixlib=rb-1.1.0&rect=10%2C0%2C2378%2C1084&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A failed experiment led to researchers showing that assumptions about chromosomal behaviour were wrong.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><iframe style="width: 100%; height: 100px; border: none; position: relative; z-index: 1;" allowtransparency="" allow="clipboard-read; clipboard-write" src="https://narrations.ad-auris.com/widget/the-conversation-canada/learning-from-failures-support-for-scientific-research-needs-to-include-when-things-dont-work-out" width="100%" height="400"></iframe>
<p>The cellular processes involved in gene regulation can be unexpectedly complicated. The expression of genes — the when, where and how much of gene activity — underlies all of biology, but is surprisingly poorly understood. </p>
<p>A recent paper published by our research group <a href="https://doi.org/10.1093/genetics/iyac181">generates as many questions as answers</a>, but gives some explanations to possible mechanisms underlying the tangle of gene function. And notably, this published research shouldn’t exist, given the way we generally fund and support scientific research.</p>
<h2>Complexity and genetic regulation</h2>
<p>Biological complexity — the gloriously complicated and convoluted living world around us — is driven by regulation and specificity. </p>
<p>Essentially, every cell in a multicellular organism has the same set of genes known as their genome. What gives cells their unique identity — what makes a skin cell a skin cell and not a muscle cell — is their specific set of genes that are turned on or off. This regulation process is incredibly specific but frustratingly messy, and follows staggeringly tangled webs of rules. </p>
<p>This complexity makes the details of regulation of gene activity one of the great unknowns of modern biology.</p>
<p>In our paper, we explore how chromosomes physically interact and share information, how that sharing substantially modifies gene expression, and how that modification varies drastically between individuals. All three of these points explain some of the complexity in gene expression, but all three have been largely ignored in conventional modelling of gene regulation.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/544713/original/file-20230825-27-l9lc4q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="an x shaped 3-d figure coloured pink and yellow floating among other similar blue shapes" src="https://images.theconversation.com/files/544713/original/file-20230825-27-l9lc4q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/544713/original/file-20230825-27-l9lc4q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/544713/original/file-20230825-27-l9lc4q.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/544713/original/file-20230825-27-l9lc4q.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/544713/original/file-20230825-27-l9lc4q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/544713/original/file-20230825-27-l9lc4q.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/544713/original/file-20230825-27-l9lc4q.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Geneticists have long assumed that chromosomes operate independently, but a failed research experiment showed that this was not the case.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
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<p>Geneticists have been taught that chromosomes are independent, don’t modify each other’s expression and that gene expression is similar between individuals. Except they aren’t, they do and it isn’t. </p>
<h2>Chromosomal communication</h2>
<p>In a process called <a href="https://doi.org/10.1016/j.cub.2017.08.001">transvection</a>, pairs of chromosomes physically couple, modifying the expression of the genes they contain. We studied the phenomena in fruit flies using an unusual genetic situation we had created by pairing a series of chromosomes with small genetic deletions that inactivate a gene with wild, functional chromosomes. </p>
<p>Other labs have shown that chromosome pairing is part of <a href="https://doi.org/10.1038/s41467-022-31737-y">normal gene regulation</a> and <a href="https://doi.org/10.1016/j.celrep.2022.111910">development</a>. But pairing errors similar to the ones in our study do occur, and they drive at least one type of <a href="https://doi.org/10.1371/journal.pgen.1000176">human cancer</a>. </p>
<p>Transvection is <a href="https://doi.org/10.1016/j.gde.2016.03.002">a widespread process</a> and a powerful example of the hidden complexity of gene regulation. </p>
<p>It is also an example of research we would not have pursued if not for some uncommon direction and mentoring Thomas Merritt, a co-author of this article, received just before starting his own lab.</p>
<p>Our transvection project started as a <a href="https://doi.org/10.1534/genetics.105.048249">failed experiment</a> while Merritt worked in evolutionary geneticist Walt Eanes’s <a href="https://life2.bio.sunysb.edu/ee/eaneslab/">lab at Stony Brook University</a>. As part of a study on metabolic interactions in flies, Merritt had edited a gene to produce a specific level of protein activity. Although the editing worked, there was much higher than expected levels of protein <a href="https://doi.org/10.1534/genetics.111.133231">and gene activity</a>. The experiment had failed. </p>
<p>Fortunately, Eanes explicitly guided researchers under his mentorship to pay attention to the unexpected, including failed experiments, and use them as an opportunity to question assumptions. </p>
<p>Two decades later, <a href="http://www.boscogeneticslab.com/people2">working alongside</a> <a href="https://www.bowdoin.edu/profiles/faculty/jbateman/">other scientists</a>, we’re still <a href="https://www.transvection.org/">finding new complications in genetics</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/544715/original/file-20230825-17-rz04it.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="a small fly" src="https://images.theconversation.com/files/544715/original/file-20230825-17-rz04it.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/544715/original/file-20230825-17-rz04it.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/544715/original/file-20230825-17-rz04it.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/544715/original/file-20230825-17-rz04it.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/544715/original/file-20230825-17-rz04it.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/544715/original/file-20230825-17-rz04it.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/544715/original/file-20230825-17-rz04it.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Studying the genome of Drosophila melanogaster reveals how chromosomes interact with and affect each genetic expression.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
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</figure>
<h2>Failed experiments and scientific assumptions</h2>
<p>That initial experiment had failed — but it had done so for a very interesting reason. That failed experiment, and the series of studies that followed it, showed that what geneticists typically think of as “<a href="https://wyss.harvard.edu/news/light-shed-on-century-old-riddle-of-chromosome-pairing/">independent</a>” chromosomes actually interact with each other through direct physical connections.</p>
<p>That failed experiment illuminated a world of complex regulatory control. Not only do genes have incredibly complex on/off switches, these switches sometimes work across and between chromosomes. </p>
<p>Handled well, these unexpected failures in the lab pushed us to question the assumptions that led to the unexpected result. Here, the failed experiment forced us to rethink the independence of chromosomes. </p>
<p>Our further studies explored how this genetic conversation was dynamic, changed <a href="https://doi.org/10.1534/g3.114.012484">in response to the environment</a> and differed between <a href="https://doi.org/10.1534/genetics.111.133231">individuals</a>.</p>
<h2>Individual variation</h2>
<p>The dynamic gene regulation and individual variation that allows multicellularity is also a central player in disease and individuality. For example, why do some people, but not others, respond to cancer treatments or even fall victim to cancer in the first place? </p>
<p>A better appreciation of individual variation is one of the major advances of our paper. Knowing that the amount of communication between chromosomes varies substantially across individuals and our work begins to shed light on the genes and mechanisms behind that variation. </p>
<p>These are important steps towards a more complete understanding of gene regulation and the misregulation that leads to diseases like <a href="https://openoregon.pressbooks.pub/mhccmajorsbio/chapter/cancer-and-gene-regulation/">cancer</a>. </p>
<h2>Dynamic science</h2>
<p>Science advances when scientists push boundaries and explore, not when we repeat or timidly inch forward. Too often we try to avoid or prevent failure. Funding agencies may also hesitate to fund projects seen as <a href="https://www.science.org/content/article/audacity-part-3-funding-audacious-science">risky</a>. </p>
<p>Science needs a culture that promotes risk and exploring the unexpected.</p>
<p>And while we turn to science to address emerging crises, we are not supporting the necessary scientific development. Think of the increasingly frequent <a href="https://theconversation.com/canadians-are-unprepared-for-natural-hazards-heres-what-we-can-do-about-it-201863">climate disasters</a>, the <a href="https://theconversation.com/the-quest-for-delicious-decaf-coffee-could-change-the-appetite-for-gmos-153032">challenges of feeding an exploding global population</a>, <a href="https://doi.org/10.1038/s41586-019-1717-y">the ongoing global pandemic</a> and <a href="https://www.nytimes.com/2023/06/16/opinion/cancer-treatment-disparities.html">cancer</a>.</p>
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Read more:
<a href="https://theconversation.com/doctors-are-drowning-in-a-tsunami-of-liver-disease-and-cancer-98061">Doctors are drowning in a tsunami of liver disease and cancer</a>
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<p>All of these issues will require novel solutions and dynamic approaches that scientific funding agencies should <a href="https://www.forbes.com/sites/drdonlincoln/2021/06/28/why-you-should-care-about-federally-funded-science/">acknowledge and support</a>.</p>
<p>Breakthroughs in understanding require dynamic science and scientists who are supported to explore, ask unusual questions and, occasionally, fail in the lab. Sometimes the most important results from an experiment are the questions it forces us to ask.</p><img src="https://counter.theconversation.com/content/212073/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Thomas Merritt receives funding from the Natural Sciences and Engineering Research Council of Canada.</span></em></p><p class="fine-print"><em><span>Teresa Rzezniczak does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>A failed experiment led the researchers to question their assumptions and realize that, contrary to popular belief, chromosomes interact with and affect genetic expression.Thomas Merritt, Professor, Chemistry and Biochemistry, Laurentian UniversityTeresa Rzezniczak, PhD Candidate, Biomolecular Sciences, Laurentian UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1847232023-08-22T21:54:17Z2023-08-22T21:54:17ZNew research into genetic mutations may pave the way for more effective gene therapies<figure><img src="https://images.theconversation.com/files/543314/original/file-20230817-8328-bdaz8a.jpg?ixlib=rb-1.1.0&rect=44%2C0%2C5000%2C3315&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A lab dish containing embryos that have been injected with Cas9 protein and PCSK9 sgRNA is seen in a laboratory in Shenzhen in southern China's Guangdong province.</span> <span class="attribution"><span class="source">(AP Photo/Mark Schiefelbein)</span></span></figcaption></figure><iframe style="width: 100%; height: 100px; border: none; position: relative; z-index: 1;" allowtransparency="" allow="clipboard-read; clipboard-write" src="https://narrations.ad-auris.com/widget/the-conversation-canada/new-research-into-genetic-mutations-may-pave-the-way-for-more-effective-gene-therapies" width="100%" height="400"></iframe>
<p>Consider a living cell, which can have thousands of genes. Now think of these genes as dials that can be tweaked to change how the cell grows in a given environment. Tweaking a gene can either increase or decrease growth, and this is made more complex considering these dials are interconnected with each other, like cogs in a machine. </p>
<p>While scientists are now able to edit genes in laboratory conditions and attempt to produce findings that may lead to cures, evolution has been doing this for billions of years. Evolution is the natural process that turns these dials, allowing populations to adapt. However, unlike scientists, evolution turns these dials randomly as mutations affect the function of genes.</p>
<p>One underlying hypothesis in evolutionary theory — the evolutionary contingency hypothesis — has been that this tuning can have chaotic behaviours. Or, in other words, dials tweaked early in the process can dramatically alter later evolutionary potential.</p>
<p>Stephen Jay Gould was a famous proponent of this theory, arguing in his 1989 book <a href="https://wwnorton.com/books/9780393307009"><em>Wonderful Life</em></a> that since beneficial mutations occur randomly, chance must play an important role in evolutionary diversification.</p>
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Read more:
<a href="https://theconversation.com/does-our-dna-really-determine-our-intelligence-and-health-199266">Does our DNA really determine our intelligence and health?</a>
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<p>If this hypothesis is true, it affects how scientists should edit genes in the laboratory as they will face the chaotic interconnections of our cells. Our work set out to test this hypothesis.</p>
<h2>Resolving an evolutionary paradox</h2>
<p>We can observe the process of evolution in the laboratory under extremely well-controlled conditions. We have done so by growing populations of micro-organisms for hundreds — <a href="https://doi.org/10.7554/eLife.63910">even thousands — of days</a>. </p>
<p>Since these organisms divide and reproduce so quickly, this process represents thousands of generations of growth. These experiments have allowed us to pinpoint <a href="https://doi.org/10.1038/s41586-019-1749-3">precisely when</a>, and how, beneficial mutations co-occur and compete to take over the population.</p>
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<img alt="Image of a human genome." src="https://images.theconversation.com/files/543310/original/file-20230817-41912-psfxhj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/543310/original/file-20230817-41912-psfxhj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=418&fit=crop&dpr=1 600w, https://images.theconversation.com/files/543310/original/file-20230817-41912-psfxhj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=418&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/543310/original/file-20230817-41912-psfxhj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=418&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/543310/original/file-20230817-41912-psfxhj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=525&fit=crop&dpr=1 754w, https://images.theconversation.com/files/543310/original/file-20230817-41912-psfxhj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=525&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/543310/original/file-20230817-41912-psfxhj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=525&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Image readout of a human genome.</span>
<span class="attribution"><span class="source">(NHGRI via AP)</span></span>
</figcaption>
</figure>
<p>One striking observation from every single one of these experiments is that increases in fitness slow down over time at a rate that is surprisingly reproducible. Despite accumulating different mutations, different populations show remarkably predictable diminishing returns in how fast they adapt.</p>
<p>In contrast with the seemingly chaotic behaviour of mutations, fitness or growth changes are highly predictable. This has led many to hypothesize that this order of mutation is an <a href="https://doi.org/10.3389/fgene.2015.00099">inherent consequence</a> of the way biological systems have evolved. </p>
<p>This striking hypothesis is at odds with the idea that the <a href="https://doi.org/10.1038/s41559-020-01286-y">specifics of an organism’s biology matter for evolution</a>. In other words, it has been difficult to prove that the order in which evolution turns dials has any impact on the future.</p>
<h2>The answer to the paradox</h2>
<p>My team was able to show that the answer to resolving this paradox lies within the interconnected gene network of the cell itself. </p>
<p>For evolution to work, the dial-tuning must be precise: even if the net outcome is beneficial, adjusting one set of linked dials can trickle down and affect other previously correctly placed dials. As evolution continues, the probability of breaking harmoniously-tuned dials grows. This seemingly simple principle explains why the rate of evolutionary improvements typically slows down over time. </p>
<figure class="align-center ">
<img alt="A tray containing human DNA samples ready for genetic sequencing." src="https://images.theconversation.com/files/543312/original/file-20230817-23-a743da.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/543312/original/file-20230817-23-a743da.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=521&fit=crop&dpr=1 600w, https://images.theconversation.com/files/543312/original/file-20230817-23-a743da.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=521&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/543312/original/file-20230817-23-a743da.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=521&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/543312/original/file-20230817-23-a743da.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=654&fit=crop&dpr=1 754w, https://images.theconversation.com/files/543312/original/file-20230817-23-a743da.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=654&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/543312/original/file-20230817-23-a743da.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=654&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A tray containing human DNA samples ready for genetic sequencing.</span>
<span class="attribution"><span class="source">(AP Photo/Patricia McDonnell)</span></span>
</figcaption>
</figure>
<p>Resolving this paradox experimentally was not an easy task. After all, how can one show the entanglement of dials within the cell? <a href="https://doi.org/10.1126/science.abm4774">In our recent study</a>, we tackled this challenge by systematically trying out every possible combination of 10 key beneficial mutations and looking at how they affect the growth of cells.</p>
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<strong>
Read more:
<a href="https://theconversation.com/human-genome-editing-offers-tantalizing-possibilities-but-without-clear-guidelines-many-ethical-questions-still-remain-200983">Human genome editing offers tantalizing possibilities – but without clear guidelines, many ethical questions still remain</a>
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<p>By testing out combinations of mutations, we were able to reliably understand which mutations were entangled together (this entanglement is known as epistasis) and for just 10 mutations, over 1,000 combinations had to be generated.</p>
<h2>How this affects genetic precision medicine</h2>
<p>Current futuristic technologies tout the ability to generate precise single mutations within our own genomes with the hope that this can be used to repair non-functional genetic variants. For example, <a href="https://doi.org/10.1038/s41586-019-1711-4">prime editing</a> is an effective “search-and-replace” genome editing technology.</p>
<p>One important concern with these approaches is they can introduce undesired mutations at the same time. However, even as scientists solve these concerns, the field of human genetics has often <a href="https://doi.org/10.1038/s41576-019-0127-1">overlooked the importance of the interconnectedness of genes</a>.</p>
<p>Our study demonstrates that bioengineers should think not only about the effect a mutation has on the gene it is in, but also about the effect of the mutation in the context of all other variations in our genomes. Altering the function of any of our genes can affect our interconnected cellular networks. </p>
<p>This is compounded by the fact that all of us carry hundreds of extremely rare variants, which means each of us carries a unique interconnected network of genes. These personalized networks make us who we are. </p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/somatic-genome-editing-therapies-are-becoming-a-reality-but-debate-over-ethics-equitable-access-and-governance-continue-201234">Somatic genome editing therapies are becoming a reality – but debate over ethics, equitable access and governance continue</a>
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<p>Genome interpretation is at the heart of genetic testing for disease. And while scientists have made some progress in identifying key pathogenic genetic variants (those that can cause disease), our findings demonstrate that classifying a variant as pathogenic or benign requires us to also understand how the other genetic dials in our cells are tuned.</p><img src="https://counter.theconversation.com/content/184723/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Alex Nguyen Ba receives funding from the Natural Sciences and Engineering Research Council of Canada. </span></em></p>New research sheds light on the interconnected nature of the human genome and what this means for future gene therapies.Alex Nguyen Ba, Assistant Professor, Biology, University of TorontoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2100362023-07-26T12:15:25Z2023-07-26T12:15:25ZFragile X syndrome often results from improperly processed genetic material – correctly cutting RNA offers a potential treatment<figure><img src="https://images.theconversation.com/files/538608/original/file-20230720-23-yssm44.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2308%2C1298&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">For many people with fragile X, the mutated gene that causes symptoms is active rather than silenced.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/fragile-x-chromosome-illustration-royalty-free-illustration/1407268269">Thom Leach/Science Photo Library</a></span></figcaption></figure><p><a href="https://www.cdc.gov/ncbddd/fxs/features/fragile-x-five-things.html">Fragile X syndrome</a> is a genetic disorder caused by a mutation in a gene that lies at the tip of the X chromosome. It is linked to autism spectrum disorders. People with fragile X experience a range of symptoms that include cognitive impairment, developmental and speech delays and hyperactivity. They may also have some physical features such as large ears and foreheads, flabby muscles and poor coordination.</p>
<p>Along with our colleagues <a href="https://scholar.google.com/citations?user=fbDXtcUAAAAJ&hl=en">Jonathan Watts</a> and <a href="https://www.rushu.rush.edu/faculty/elizabeth-m-berry-kravis-md-phd">Elizabeth Berry-Kravis</a>, <a href="https://profiles.umassmed.edu/display/133116">we are</a> <a href="https://scholar.google.com/citations?user=syYm8JMAAAAJ&hl=en">a team</a> of scientists with expertise in molecular biology, nucleic acid chemistry and pediatric neurology. We recently discovered that the mutated gene responsible for fragile X syndrome is active in most people with the disorder, not silenced as previously thought. But the affected gene on the X chromosome is still unable to produce the protein it codes for because the <a href="https://doi.org/10.1073/pnas.2302534120">genetic material isn’t properly processed</a>. Correcting this processing error suggests that a potential treatment for symptoms of fragile X may one day be available.</p>
<h2>Repairing faulty RNA splicing</h2>
<p>The <a href="https://doi.org/10.1038/s41583-021-00432-0">FMR1 gene encodes a protein</a> that regulates protein synthesis. A lack of this protein leads to overall excessive protein synthesis in the brain that results in many of the symptoms of fragile X. </p>
<p>The mutation that causes fragile X results in extra copies of a DNA sequence called a <a href="https://doi.org/10.1038/s41583-021-00432-0">CGG repeat</a>. Everyone has CGG repeats in their FMR1 gene, but typically fewer than 55 copies. Having 200 or more CGG repeats silences the FMR1 gene and results in fragile X syndrome. However, we found that <a href="https://doi.org/10.1073/pnas.2302534120">around 70% of people</a> with fragile X still have an active FMR1 gene their cellular machinery can read. But it is mutated enough that it is unable to direct the cell to produce the protein it encodes.</p>
<p>Genes are transcribed into another form of genetic material called RNA that cells use to make proteins. Normally, genes are processed before transcription in order to make a readable strand of RNA. This involves removing the <a href="https://www.genome.gov/genetics-glossary/Intron">noncoding sequences</a> that interrupt genes and splicing the genetic material back together. For people with fragile X, the cellular machinery that does this cutting incorrectly splices the genetic material, such that the protein the FMR1 gene codes for is not produced.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/ypsEJcyouy8?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Fragile X syndrome is the most common inherited form of intellectual disability.</span></figcaption>
</figure>
<p>Using cell cultures in the lab, we found that <a href="https://doi.org/10.1073/pnas.2302534120">correcting this missplice</a> can restore proper RNA function and produce the FMR1 gene’s protein. We did this by using short bits of DNA called <a href="https://doi.org/10.3390%2Fjcm9062004">antisense oligonucleotides, or ASOs</a>. When these bits of genetic material bind to RNA molecules, they change the way the cell can read it. That can have effects on which proteins the cell can successfully produce.</p>
<p>ASOs have been used with spectacular success to treat other childhood disorders, such as <a href="https://doi.org/10.1016/j.tins.2020.11.009">spinal muscular atrophy</a>, and are now being used to treat <a href="https://doi.org/10.1146/annurev-pharmtox-010919-023738">a variety of neurological diseases</a>.</p>
<h2>Beyond mice models</h2>
<p>Notably, fragile X syndrome is most often <a href="https://doi.org/10.1242/dmm.049485">studied using mouse models</a>. However, because these mice have been genetically engineered to lack a functional FMR1 gene, they are quite different from people with fragile X. In people, it is not a missing gene that causes fragile X but mutations that lead the existing gene to lose function. </p>
<p>Because the mouse model of fragile X lacks the FMR1 gene, the RNA is not made and so cannot be misspliced. Our discovery would not have been possible if we used mice.</p>
<p>With further research, future studies in people may one day include injecting ASOs into the cerebrospinal fluid of fragile X patients, where it will travel to the brain and hopefully restore proper function of the FMR1 gene and improve their cognitive function.</p><img src="https://counter.theconversation.com/content/210036/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Joel Richter receives funding from NIH and FRAXA. </span></em></p><p class="fine-print"><em><span>Sneha Shah receives funding from the FRAXA Research Foundation.</span></em></p>Fragile X syndrome is the most common inherited form of intellectual disability. Using short bits of DNA to fix improperly transcribed genes may one day be a potential treatment option.Joel Richter, Professor of Neuroscience, UMass Chan Medical SchoolSneha Shah, Assistant Professor of Molecular Medicine, UMass Chan Medical SchoolLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2094262023-07-13T14:06:55Z2023-07-13T14:06:55ZMale rhesus macaques often have sex with each other – a trait they have inherited in part from their parents<figure><img src="https://images.theconversation.com/files/536818/original/file-20230711-17-aibxh5.jpg?ixlib=rb-1.1.0&rect=941%2C102%2C3853%2C3154&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Male same-sex sexual behaviour was widespread in a population of rhesus macaques.</span> <span class="attribution"><span class="source">Sam Edwards</span>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span></figcaption></figure><p>Homosexual behaviour is not limited to humans. Biologists have reported homosexual behaviour in many species of wild animal, ranging from <a href="https://doi.org/10.1371/journal.pone.0166024">bats</a> and <a href="https://doi.org/10.1016/j.anbehav.2010.05.009">birds</a> to <a href="https://doi.org/10.1016/j.tree.2009.03.014">dolphins</a> and <a href="https://doi.org/10.1163/1568539X-bja10062">primates</a>. </p>
<p>When animals engage in homosexual behaviour, one might assume that they invest less time and energy on reproduction. This suggests that there may be strong reproductive costs associated with such behaviour, such as having fewer offspring. So it raises the question of how homosexual behaviour manages to evolve and continue to exist within a population.</p>
<p>The underlying presumption is that there is not only a cost associated with engaging in homosexual activity, but also that variation in such behaviour is passed down from one generation to the next. Called heritability, this is essential for any evolution by natural selection to occur. </p>
<p>We set out to investigate these issues by studying 236 male <a href="https://www.britannica.com/animal/rhesus-monkey">rhesus macaques</a> living freely in a colony of 1,700 monkeys on the tropical island of Cayo Santiago, Puerto Rico. We observed these monkeys for three years and <a href="https://doi.org/10.1038/s41559-023-02111-y">found that</a> male same-sex sexual behaviour (SSB) was widespread. In fact, 72% of the males we observed mounted other males, while only 46% mounted females.</p>
<p>Critically, male SSB is not unique to this population of macaques. We saw similar behaviour in wild rhesus macaque populations in northern Thailand. And there have been <a href="https://www.google.com/books/edition/Primate_Behavior/QingBAAAQBAJ?hl=en&gbpv=0">previous reports</a> of SSB in this species from India, too.</p>
<figure class="align-center ">
<img alt="A rhesus macaque colony." src="https://images.theconversation.com/files/536787/original/file-20230711-30-f7j44b.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/536787/original/file-20230711-30-f7j44b.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=402&fit=crop&dpr=1 600w, https://images.theconversation.com/files/536787/original/file-20230711-30-f7j44b.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=402&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/536787/original/file-20230711-30-f7j44b.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=402&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/536787/original/file-20230711-30-f7j44b.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=505&fit=crop&dpr=1 754w, https://images.theconversation.com/files/536787/original/file-20230711-30-f7j44b.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=505&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/536787/original/file-20230711-30-f7j44b.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=505&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A rhesus macaque colony in Rajasthan, India.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/rhesus-monkey-colony-alwar-rajasthan-india-159063821">Attila JANDI/Shutterstock</a></span>
</figcaption>
</figure>
<h2>From one generation to the next</h2>
<p>We also had access to pedigree records that traced the parentage of each macaque back to 1956. This allowed us to explore the effect of relatedness (heritability) on their behaviour, taking into account other factors that could influence the results, such as age and social group structure.</p>
<p>We found that the heritability of male SSB was 6.4%, meaning genetics do account for a small proportion of SSB – the rest is environmental.</p>
<p>We calculated “evolvability” to be 14.9%, giving the potential rate at which the trait can evolve per generation through natural selection. Evolvability is thought to be a more reliable indicator than heritability of the degree to which genetics can respond to evolutionary pressure, and provides us with further evidence that SSB can evolve through selection.</p>
<p>Our estimates align with what we would expect for a behavioural trait that is probably influenced by multiple genetic factors and environmental effects. They are also consistent with heritability values reported in studies of other social behaviour in primate species, including <a href="https://doi.org/10.1093/evolut/qpad066">social grooming in baboons</a> and <a href="https://doi.org/10.1038/s41437-022-00558-6">social proximity in capuchins</a>. </p>
<p>We also found a genetic correlation between the number of times a male was observed mounting another male and the number of times he was mounted by other males. This suggests that different forms of SSB in these monkeys share a common genetic basis.</p>
<figure class="align-center ">
<img alt="Two grooming chacma baboons on a tree." src="https://images.theconversation.com/files/536773/original/file-20230711-25-fgafa9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/536773/original/file-20230711-25-fgafa9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/536773/original/file-20230711-25-fgafa9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/536773/original/file-20230711-25-fgafa9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/536773/original/file-20230711-25-fgafa9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/536773/original/file-20230711-25-fgafa9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/536773/original/file-20230711-25-fgafa9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Two chacma baboons grooming eachother. Caprivi, Namibia.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/two-grooming-chacma-baboons-papio-ursinus-2250991039">Fotografie-Kuhlmann/Shutterstock</a></span>
</figcaption>
</figure>
<h2>What underpins this behaviour?</h2>
<p><a href="https://doi.org/10.1126/science.aat7693">Previous studies</a> on the heritability of SSB have primarily focused on humans. However, these studies often rely on self-reported data, which can introduce complications. The cultural stigma surrounding homosexuality, for instance, could lead to the underreporting of homosexual activity.</p>
<p>Heritability of SSB has also been found in some invertebrate species, including <a href="https://doi.org/10.1186/s12862-016-0658-4">seed beetles</a> and <a href="https://doi.org/10.1098/rspb.2015.0429">fruit flies</a>. However, the pathways through which SSB develops in these species are thought to be different from those observed in social vertebrates like primates. For example, factors such as <a href="https://doi.org/10.1007/s00265-013-1610-x">imperfect sex recognition</a> are believed to influence the development of SSB in invertebrates.</p>
<p>Demonstrating that SSB is heritable and its potential for evolutionary response to natural selection is an important first step towards understanding the factors that influence variation in this behaviour. </p>
<p>Many evolutionary theories for SSB in animals exist. But they all depend on the behaviour showing a degree of heritability. </p>
<p>One theory suggests that in some species, animals may engage in SSB because it serves a <a href="https://doi.org/10.1016/j.anbehav.2007.02.001">beneficial social function</a>. For example, it may strengthen the bonds between males, ultimately benefiting them during competition for mates and food. </p>
<p>In support of this theory, our research found that male rhesus macaques involved in SSB partnerships were more likely to support each other in conflicts with other individuals. This effect could be a way in which SSB benefits a macaque and its chances of producing offspring, thereby allowing the behaviour and the genes associated with it to persist within a population.</p>
<figure class="align-center ">
<img alt="A group of macaques fighting." src="https://images.theconversation.com/files/536779/original/file-20230711-15-ln4ks.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/536779/original/file-20230711-15-ln4ks.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=267&fit=crop&dpr=1 600w, https://images.theconversation.com/files/536779/original/file-20230711-15-ln4ks.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=267&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/536779/original/file-20230711-15-ln4ks.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=267&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/536779/original/file-20230711-15-ln4ks.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=335&fit=crop&dpr=1 754w, https://images.theconversation.com/files/536779/original/file-20230711-15-ln4ks.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=335&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/536779/original/file-20230711-15-ln4ks.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=335&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Rhesus macaques involved in SSB partnerships were more likely to support each other in conflicts.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/group-macaques-fighting-1998316622">Di Qin/Shutterstock</a></span>
</figcaption>
</figure>
<h2>Learning from primates</h2>
<p>So what can we learn from these findings about SSB across primate species, including humans?</p>
<p>A <a href="https://doi.org/10.1126/science.aat7693">previous study</a> examining SSB heritability in humans found significant reproductive costs associated with this behaviour. In contrast, we found no such costs in macaques. </p>
<p>This suggests that the costs associated with human SSB might arise from specific social factors unique to humans. However, more research is needed to explore this idea further.</p>
<p>Today, some people still believe that SSB is rare or the product of extreme and unusual environmental conditions, and selectively look to examples in nature to validate their view. Our results may help to challenge these beliefs and combat prejudice against homosexuality and bisexuality. However, society’s moral obligation to strive for more inclusivity and acceptance of different sexual orientations ultimately does not rely on observations from the natural world.</p><img src="https://counter.theconversation.com/content/209426/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jackson Clive received funding for this work from the UK Natural Environment Research Council, the American Institute of Bisexuality and the Genetics Society.</span></em></p><p class="fine-print"><em><span>Ewan Flintham receives funding from the UK Natural Environment Research Council
. </span></em></p><p class="fine-print"><em><span>Vincent Savolainen receives funding from NERC, the American Institute of Bisexuality and the Evolution, Education Trust. </span></em></p>Most of the males in a Puerto Rican monkey colony engaged in homosexual activity, a new study reveals.Jackson Clive, Postdoctoral Researcher, Imperial College LondonEwan Flintham, Postdoctoral Researcher, Université de LausanneVincent Savolainen, Professor of Organismic Biology, Imperial College LondonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2075932023-06-28T18:10:56Z2023-06-28T18:10:56ZEnglish dialects make themselves heard in genes<figure><img src="https://images.theconversation.com/files/534597/original/file-20230628-21-5cad3t.jpg?ixlib=rb-1.1.0&rect=289%2C118%2C4440%2C3103&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Conditions in rural England around the turn of the 20th century offer a case study for cultural evolution researchers.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/coming-home-from-the-marshes-1886-a-work-made-of-platinum-news-photo/1338669913">Heritage Images/Hulton Archive via Getty Images</a></span></figcaption></figure><p>If you need to hit a nail, what tool do you ask for? If you say “hammer,” do you pronounce the “<a href="https://www.bl.uk/british-accents-and-dialects/articles/phonological-variation-across-the-uk#:%7E:text=Above%20all%20he%20is%20a%20rhotic%20speaker">r</a>”? Do you drop the “<a href="https://www.bl.uk/british-accents-and-dialects/articles/social-variation-across-the-uk#:%7E:text=and%20happens.-,H%2Ddropping,-%E2%80%93%20the%20tendency%20to">h</a>”?</p>
<p>Different people pronounce the same English words in different ways. People learn which words to use and how to pronounce them as they’re learning to talk with family, friends and others in their community, so geographic patterns in these pronunciations can <a href="https://www.theguardian.com/science/2022/jul/31/north-south-english-dialects-language-pronunciation-study">persist over time</a>.</p>
<p>In England, pairs of words that mean similar things, like “sight” and “vision” or “yes” and “aye,” can reveal a rich history of language that is intertwined with the history of the place itself. Such words have their origins in <a href="https://education.nationalgeographic.org/resource/norman-conquest/">migrations and conquests</a> that took place during the Middle Ages. New words would sometimes coexist and sometimes displace one another.</p>
<p><a href="https://scholar.google.com/citations?user=06-OHeUAAAAJ&hl=en&oi=ao">Cultural evolution researchers</a> <a href="https://scholar.google.com/citations?user=vwQdgAYAAAAJ&hl=en&oi=ao">like us</a> know that it’s not just mountain ranges or oceans that can be barriers to interaction. Different people can share their technology, cuisines and ideas, but some tend to interact more often with those who share cultural similarities, <a href="https://doi.org/10.1146/annurev.soc.27.1.415">a behavior called homophily</a>.</p>
<p>This can be seen most clearly when cultural traditions lead people to marry people from the same community. Populations that tend to marry within their group because of <a href="https://doi.org/10.1186/1742-4755-6-17">social or economic forces</a>, including <a href="https://doi.org/10.1038/srep35837">religious</a> <a href="https://www.science.org/content/article/tracing-roots-jewishness-rev2">traditions</a> and <a href="https://www.nytimes.com/2017/07/17/health/india-south-asia-castes-genetics-diseases.html">social stratification</a>, have smaller gene pools, leading them to be more genetically similar to one another.</p>
<p>In addition to groups with distinctive marital practices, researchers have found relationships between genes and culture when studying groups that are <a href="https://doi.org/10.1371/journal.pgen.1003316">from different ethnicities</a> or <a href="https://doi.org/10.1073/pnas.94.15.7719">different regions of the world</a>. These similarities between genes and culture don’t imply that certain genetic variants are exclusive to these groups, or that genetics causes certain cultures to arise. Rather, the same people might be more likely to share genetics and language because of a common history, especially because of significant geographic or social barriers between groups.</p>
<p>Can smaller things, like the different dialects between neighboring villages, shape the genetic landscape of populations? In our <a href="https://doi.org/10.1002/ajpa.24789">new study</a>, we combined genetic and linguistic data sampled in England to study the effects of culture on genetics at smaller geographic scales than generally studied.</p>
<p>We examined this relationship between cultural and genetic variation across England. In places where people move often, the small correlations between language and genes can be lost because of how rapidly they change. Since Great Britain is an island, <a href="https://doi.org/10.1111/1468-0289.00221">few people entered its rural population</a> between the times of the Norman conquest in 1066 and the end of the 19th century, making it ideal for our analysis.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/534599/original/file-20230628-19-htd5ou.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="two women and three children in 1956 collect water from a tub against a stone wall of a house" src="https://images.theconversation.com/files/534599/original/file-20230628-19-htd5ou.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/534599/original/file-20230628-19-htd5ou.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=493&fit=crop&dpr=1 600w, https://images.theconversation.com/files/534599/original/file-20230628-19-htd5ou.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=493&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/534599/original/file-20230628-19-htd5ou.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=493&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/534599/original/file-20230628-19-htd5ou.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=620&fit=crop&dpr=1 754w, https://images.theconversation.com/files/534599/original/file-20230628-19-htd5ou.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=620&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/534599/original/file-20230628-19-htd5ou.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=620&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">In the middle of the 20th century, interviewers recorded the ways rural people spoke.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/village-without-water-at-ruyton-xi-towns-shropshire-churns-news-photo/867461430">Bill Ellman/Mirrorpix via Getty Images</a></span>
</figcaption>
</figure>
<h2>Combining two sets of data</h2>
<p>Ideally, we could use a unified data set capturing information about the genetics and dialects of people living in a region. Unfortunately, no such data exists. Instead, we used data from two separate studies of people from approximately the same time and place. For our research, we focused on where the data sets overlapped in England.</p>
<p>For linguistic data, we relied on the <a href="https://dialectandheritage.org.uk/about/the-survey-of-english-dialects/">Survey of English Dialects</a>. Between 1950 and 1961, interviewers visited over 300 mostly rural places and asked people hundreds of questions about their daily lives. Their answers recorded the phrases, terms and sounds of local dialects of English. Each of these words can carry clues about where, or with whom, a person grew up.</p>
<p>The genetic data we used came from the <a href="https://www.peopleofthebritishisles.org/">People of the British Isles</a> project, an academic investigation of how much Britain’s historical events of conquest, war and migration are reflected in British genetics. The project sequenced DNA from more than 2,000 people in Great Britain and Northern Ireland. Researchers genotyped people whose grandparents who were born within 50 miles (80 kilometers) of each other, were largely rural, and were born in the late 19th century.</p>
<p>The People of the British Isles project found that most genotypes were not local to any one part of Great Britain <a href="https://doi.org/10.1038/nature14230">but were evenly distributed</a>. However, the historical movements of people to Great Britain left genetic marks: Compared with people in the rest of Great Britain, the genetics of those from the south of England were slightly more similar to those in France – a result of the Norman conquest a millennium ago – and the genetics of people in the former <a href="https://www.britannica.com/place/Danelaw">Danelaw</a> were slightly more similar to modern Danes – because of the settling of the region by Vikings and, later, Danes. These events resulted in groups of people with somewhat similar genetics, a phenomenon <a href="https://doi.org/10.1126/science.1078311">referred to as genetic clustering</a>.</p>
<p>We used features from the Survey of English Dialects to measure where neighboring towns spoke the most differently, which occurs at the borders between dialects. When people from neighboring towns speak the same dialect, we expect features of their language, such as whether the “r” is pronounced at the ends of words, to be similar. Conversely, if nearby towns speak different dialects, their language features will be more different.</p>
<p>Many of these dialect boundaries have long histories, such as that separating the English of the <a href="https://www.bl.uk/british-accents-and-dialects/articles/regional-voices-the-north-south-divide">North from that of the South of England</a>. Over time, <a href="https://www.theguardian.com/science/2022/jul/31/north-south-english-dialects-language-pronunciation-study">dialects can persist</a> in similar locations if geographic or cultural barriers influence how often and with whom people interact.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/534601/original/file-20230628-29-64o014.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="1938 black and white photo of postman pushing bike up hill in village" src="https://images.theconversation.com/files/534601/original/file-20230628-29-64o014.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/534601/original/file-20230628-29-64o014.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=452&fit=crop&dpr=1 600w, https://images.theconversation.com/files/534601/original/file-20230628-29-64o014.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=452&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/534601/original/file-20230628-29-64o014.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=452&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/534601/original/file-20230628-29-64o014.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=568&fit=crop&dpr=1 754w, https://images.theconversation.com/files/534601/original/file-20230628-29-64o014.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=568&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/534601/original/file-20230628-29-64o014.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=568&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Rural life was more insular in the past.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/the-postmans-job-is-not-a-happy-one-when-the-snow-is-on-the-news-photo/3288430">Fox Photos/Hulton Archive via Getty Images</a></span>
</figcaption>
</figure>
<h2>The echo of sounds long gone</h2>
<p>We found greater genetic differences at the borders between dialects. Our results suggest that language, or some other aspect of culture, has limited how people interacted to some degree over the past thousand years. By limiting how often people started families with those from neighboring groups, cultural differences have maintained genetic evidence of the Norman conquest and other events from the Middle Ages.</p>
<p>This is the first time that information about linguistic dialects has been compared with modern genetic data within a population, particularly at such a granular level. Notably, people speaking different dialects have no obvious reason to avoid marrying one another, as would be expected from groups with specific marriage customs. Nevertheless, we find that even small-scale language differences, or other aspects of culture associated with these differences, can leave an impression on genes via people’s mating behaviors.</p>
<p>Even though people outside of Britain may think of a general “British accent,” the subtle differences among dialects seem to have parallels with the genetics of the region. This is in spite of the fact that the languages brought by people coming to England have since mixed and merged to produce the modern English language and today’s dialects.</p>
<p>The data used in our study represents the genetic landscape and dialects of the late 19th century; both have changed significantly since then. After the introduction of radio and television, dialects became more influenced by the cities around them. As a result, features of many English dialects in England, such as the pronunciation of “r” at the ends of syllables, have <a href="https://www.cam.ac.uk/research/news/cambridge-app-maps-decline-in-regional-diversity-of-english-dialects">become much less common</a>.</p>
<p>At the same time, immigrants from the former British Empire and elsewhere have brought a new influx of language. The cities in Great Britain have developed a set of new dialects rooted in the interactions among people from all ethnicities. As cultural barriers among groups fall away, small human interactions form the bridges that allow people to deemphasize differences and learn from one another.</p>
<p><em>This article has been updated to clarify which parts of the United Kingdom were included in the different data sets and the authors’ study.</em></p><img src="https://counter.theconversation.com/content/207593/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Yakov Pichkar receives funding from the John Templeton Foundation (grant no. 62187). </span></em></p><p class="fine-print"><em><span>Nicole Creanza receives funding from the National Science Foundation and the John Templeton Foundation.</span></em></p>People with a common history – often due to significant geographic or social barriers – often share genetics and language. New research finds that even a dialect can act as a barrier within a group.Yakov Pichkar, Ph.D. Candidate in Biological Sciences, Vanderbilt UniversityNicole Creanza, Assistant Professor of Biological Sciences, Vanderbilt UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2045282023-06-19T20:00:41Z2023-06-19T20:00:41ZGenetics and concussion – why a minor knock can be devastating for some people<figure><img src="https://images.theconversation.com/files/528968/original/file-20230530-38788-uxzrwj.jpg?ixlib=rb-1.1.0&rect=30%2C7%2C5081%2C2682&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/portrait-young-caucasian-sports-athlete-having-471119147">Shutterstock</a></span></figcaption></figure><p>Concussion and head trauma is a real and serious risk for many Australians. While most people suffer acute and relatively short-lived effects, such as dizziness and headache, in some cases symptoms persist for weeks, months or years. It can result in long-term and debilitating neurological impairment. </p>
<p>Concussion in sport – from the junior to the elite level – is being prioritised as a public health concern in Australia. A <a href="https://www.aph.gov.au/Parliamentary_Business/Committees/Senate/Community_Affairs/Headtraumainsport">Senate inquiry</a> into concussions and repeated head trauma in contact sport is due to report in August. Of note in the hearings has been the AFL’s <a href="https://parlinfo.aph.gov.au/parlInfo/download/committees/commsen/26756/toc_pdf/Community%20Affairs%20References%20Committee_2023_04_26.pdf;fileType=application%2Fpdf#search=%22committees/commsen/26756/0000%22">acknowledgement</a> of an association between head trauma and chronic traumatic encephalopathy, a neurodegenerative disease <a href="https://www.abc.net.au/news/2023-04-26/danny-frawley-family-urges-afl-to-act-on-cte-concussion/102269648">found</a> in several deceased players. </p>
<p>The <a href="https://www.aihw.gov.au/reports/sports-injury/sports-injury-in-australia/contents/sports-injury-hospitalisations">latest data</a> show concussion can happen in nearly every sport, not just contact sports, with almost 3,100 hospitalisations for concussion caused by sports in 2020–21.</p>
<p>But not everyone responds the same way to concussion. At present, there are <a href="http://dx.doi.org/10.1136/bjsports-2017-097729">few reliable indicators</a> of who will suffer specific or long-term effects. We do know the number and severity of <a href="http://dx.doi.org/10.1136/bjsports-2017-097729">symptoms</a> and <a href="https://pubmed.ncbi.nlm.nih.gov/23508730/">multiple concussions</a> are important. And we are developing understanding of how a person’s genes play a role. </p>
<h2>Traumatic brain injury</h2>
<p>Concussion is a form of traumatic brain injury that can result in <a href="https://theconversation.com/concussions-can-cause-disruptions-to-everyday-life-in-both-the-short-and-long-term-a-neurophysiologist-explains-what-to-watch-for-192390">neurological dysfunction</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/27889010/">including</a> migraine, cognitive deficit, confusion, slowed reaction times, personality changes, drowsiness and emotional changes. Some people also suffer long-term problems with memory, thinking and other symptoms, such as anxiety and mood disturbances. </p>
<p>After brain injury there is a cascade of events that impacts the health of neurons and affects the flow of chemical ions, such as calcium, in the brain. Mutations in genes that affect the transport of neuronal ions (atoms or molecules with a positive or negative electrical charge), termed <a href="https://www.frontiersin.org/articles/10.3389/fphar.2016.00121/full#:%7E:text=Ion%20channels%20are%20membrane%20proteins,or%20physical%20and%20chemical%20stimuli.">ion channel genes</a>, can also affect how the brain works. </p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1606923959370502145"}"></div></p>
<p>The strongest evidence of a connection between concussion response and ion channel gene function is from patients with a family history of a rare type of migraine (hemiplegic migraine, which causes the sufferer to experience severe migraine associated with motor impairment and muscle weakness) and <a href="https://rarediseases.info.nih.gov/diseases/10975/familial-hemiplegic-migraine">episodic ataxia</a> (which causes bouts of movement incoordination). </p>
<p>Specific types of these severe neurogenetic disorders are caused by mutations in the calcium channel gene <a href="https://pubmed.ncbi.nlm.nih.gov/8898206/">CACNA1A</a>. Patients with these mutations can be highly sensitive to head impacts. Some <a href="https://doi.org/10.1002/ana.1031">specific mutations</a> can see very minor head trauma lead to concussion, seizures, cerebral oedema (swelling), coma and <a href="https://onlinelibrary.wiley.com/doi/full/10.1016/j.pmrj.2017.07.081">sometimes death</a>. </p>
<p>Research has also shown 35% of patients with <a href="https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-021-01309-4#:%7E:text=Most%20ATP1A2%20mutations%20cause%20familial,disability%20%5B4%2C%2027%5D.">mutations</a> in a second hemiplegic migraine ion channel gene, ATP1A2 – which is linked to hemiplegic migraine, ataxia, epilepsy and other seizures and controls brain sodium and potassium levels, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693486/">report</a> concussion symptoms following mild head trauma. </p>
<p>Focusing on all ion channel genes, our genomics lab (<a href="https://www.qut.edu.au/research/centre-for-genomics-and-personalised-health">Griffiths Centre for Genomics and Personalised Health</a>) recently studied 117 concussion-affected people. We found mutations in 21 ion channel genes, 14 of which could have an impact on concussion susceptibility or outcomes.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/concussion-almost-half-of-people-still-show-signs-of-brain-injury-after-six-months-204702">Concussion: almost half of people still show signs of brain injury after six months</a>
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<h2>Other types of genes</h2>
<p>Apart from a role for ion channel genes, there have been a number of additional genes linked by research to concussion. </p>
<p>One of the most studied is the <a href="https://www.nia.nih.gov/health/alzheimers-disease-genetics-fact-sheet">ApoE gene</a>, which is involved in transporting cholesterol in the body and has long been recognised as a risk factor for Alzheimer’s disease. Studies have indicated a variant of this gene (ApoE4) is linked with <a href="https://pubmed.ncbi.nlm.nih.gov/30848161/">poorer</a> and more <a href="https://pubmed.ncbi.nlm.nih.gov/34333069/">long-term concussion outcomes</a>. Those who carry this variant are also more likely to have significant <a href="https://scholars.mssm.edu/en/publications/association-of-apoe-genotypes-and-chronic-traumatic-encephalopath">signs</a> of brain degeneration after concussion. </p>
<p>Another genetic variation in the ApoE gene that makes it less productive has been <a href="https://pubmed.ncbi.nlm.nih.gov/18185033/">linked</a> to a higher likelihood of concussion.</p>
<p>Beyond ApoE, genes that help control a variety of brain functions have been <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910946/">suggested</a> as factors in concussion – including some <a href="https://pubmed.ncbi.nlm.nih.gov/28100103/">involved</a> in neuronal growth, dopamine receptors and, <a href="https://pubmed.ncbi.nlm.nih.gov/33017352/">most recently</a>, brain axon (nerve fibre) development. </p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/hit-your-head-while-playing-sport-heres-what-just-happened-to-your-brain-203038">Hit your head while playing sport? Here's what just happened to your brain</a>
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<h2>A predisposition for injury</h2>
<p>Questions concerning the link between genetic predisposition to injury in sport are not new. Twenty years ago, the Australian Law Reform Commission <a href="https://www.alrc.gov.au/publication/essentially-yours-the-protection-of-human-genetic-information-in-australia-alrc-report-96/">referred</a> to research showing </p>
<blockquote>
<p>[…] a milder form of this condition [CTE or punch-drunk syndrome] could occur in players of rugby, soccer and other sports associated with repetitive blows to the head.</p>
</blockquote>
<p>In 2016, the Australian Institute of Sport (AIS) released a <a href="https://pubmed.ncbi.nlm.nih.gov/27899345/">position statement</a> on the ethics of genetic testing and research in sport. But the <a href="https://www.concussioninsport.gov.au/__data/assets/pdf_file/0006/1090680/concussion-and-brain-health-position-statement-2023.pdf">latest</a> AIS Concussion and Brain Health Position Statement does not mention the use of genetic information concerning concussion-related susceptibility.</p>
<p>Currently, there is available DNA diagnostic testing for the two ion channel genes already implicated in concussion, because this testing is used for the diagnosis of familial hemiplegic migraine and episodic ataxia. But genetic testing is not currently undertaken for concussion.</p>
<p>In Australia, it is difficult to find information on whether genetic testing occurs in elite sport. In the United Kingdom, genetic testing <a href="https://doi.org/10.5114/biolsport.2018.70747">does take place</a>, although it is not common. Athletes and support staff there are <a href="https://theconversation.com/genetic-testing-is-being-used-in-sport-but-what-are-the-consequences-88604">open to the idea</a> of genetic information being used to improve sport performance and reduce injury risk.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/uncharted-brain-decoding-dementia-a-three-part-series-to-read-and-listen-to-193162">Uncharted Brain: Decoding Dementia – a three-part series to read and listen to</a>
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<h2>What’s next?</h2>
<p>It is vital there is more careful consideration of genetic factors involved in concussion development and response. Clarification of the role of ion channel gene mutations and other gene variants, along with information from additional biomarkers and imaging, will be important in developing better concussion management and treatment approaches. </p>
<p>Before introducing genetic testing, regulatory and governance frameworks would also need careful consideration. Wider ethical and legal implications will need to be fully examined including health privacy laws, privacy of genetic samples, anti-discrimination laws and employment-related laws, especially in professional sport. </p>
<p>With the growing awareness of concussion-related injury risks highlighted by the Senate inquiry, further research in Australia could also investigate attitudes toward the use of genetic testing and predisposition to injury risk in sport.</p><img src="https://counter.theconversation.com/content/204528/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Lyn Griffiths has received migraine and concussion research funding from the Australian National Health and Medical Research Council, US Migraine Research Foundation, US Dept of Defence and Teva, and in addition receives research funding for a Defence Innovation Hub from Australian Defence and from VariantBio for her Norfolk Island genetics studies. She is a member of the Human Genetics Society of Australasia and Chair of the Board of Censors for Diagnostic Genomics.</span></em></p><p class="fine-print"><em><span>Annette Greenhow receives funding from the Government of Canada Social Sciences and Humanities Research Council and previously received funding from Australian Catholic University and the City of Gold Coast Ambassador Program. She is affiliated with the Australia and New Zealand Sports Law Association as a board member (views are her own). </span></em></p>The genetic evidence behind why some people suffer longer term concussion effects is growing. But what are the ethical considerations that flow from that knowledge when it comes to sport?Lyn Griffiths, Professor, Queensland University of TechnologyAnnette Greenhow, Assistant Professor, Faculty of Law, Bond UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2000482023-05-08T12:19:31Z2023-05-08T12:19:31ZClothes moths: Why I admire these persistent, destructive, difficult-to-eradicate and dull-looking pests<figure><img src="https://images.theconversation.com/files/524520/original/file-20230504-1338-tnizp0.jpg?ixlib=rb-1.1.0&rect=78%2C103%2C1284%2C860&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">*Tineola bisselliella* can survive on as little as a hairball and some vitamin B.</span> <span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Tineola.bisselliella.7218.jpg">Olaf Leillinger/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>Every day, I come into the lab to check the moth jar. The jar, which previously housed a liter of honey, now contains a multitude of small golden moths and their wriggly caterpillar offspring.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/524198/original/file-20230503-19-qkt3kv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="smiling woman holds a liter-size jar with scrunched up knitting in it" src="https://images.theconversation.com/files/524198/original/file-20230503-19-qkt3kv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/524198/original/file-20230503-19-qkt3kv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=749&fit=crop&dpr=1 600w, https://images.theconversation.com/files/524198/original/file-20230503-19-qkt3kv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=749&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/524198/original/file-20230503-19-qkt3kv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=749&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/524198/original/file-20230503-19-qkt3kv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=941&fit=crop&dpr=1 754w, https://images.theconversation.com/files/524198/original/file-20230503-19-qkt3kv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=941&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/524198/original/file-20230503-19-qkt3kv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=941&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The author in the lab with her prized moth jar.</span>
<span class="attribution"><span class="source">Isabel Novick</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>The founding population came from within my house – pests that fervently fed on my sweaters, rugs and horsehair plaster. When they emerge from my walls in the evenings, I chase them with zeal and catch them in jam jars. “Moth!” I shout, jumping up from the couch, knocking over whatever is in front of me. In the lab, I feed them clippings of a mohair sweater that shrank in the wash, which I soak in brewer’s yeast.</p>
<p><a href="https://scholar.google.com/citations?hl=en&user=Cog3A6IAAAAJ&view_op=list_works&gmla=AHoSzlX3j284dvhFbLwvsoW_JOhIs5qvImnVBOhC7QrqXwX53uEoVh9osKUVd9oBWd7foWeY7X0W3TJBE-pg97Ik">I’m a doctoral candidate</a> <a href="https://www.bu.edu/biology/people/profiles/isabel-novick/">studying the evolutionary relationships</a> within the moth family Tineidae. I’m interested in how webbing clothes moths, <em>Tineola bisselliella</em>, have dispersed so widely and colonized our homes so readily. I am using a population genetics approach, examining the DNA of isolated populations of moths from all over the world. They eat crazy stuff. They live mostly indoors. How did this happen?</p>
<h2>Resourceful, vigorous, tanklike eating machines</h2>
<p>Webbing clothes moths are part of a distinctive, primordial lineage called the <a href="https://doi.org/10.1007/978-1-4020-6359-6_3921">fungus moth family</a>. These guys emerged long before more well-known species like silk moths. If you’re unlucky, you are already aware of the destruction they can wreak on sweaters, rugs and upholstery. But you many not realize how fascinating Tineidae are.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/524201/original/file-20230503-22-bkppfb.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="little worms on the surface of a knitted material" src="https://images.theconversation.com/files/524201/original/file-20230503-22-bkppfb.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/524201/original/file-20230503-22-bkppfb.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=437&fit=crop&dpr=1 600w, https://images.theconversation.com/files/524201/original/file-20230503-22-bkppfb.PNG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=437&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/524201/original/file-20230503-22-bkppfb.PNG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=437&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/524201/original/file-20230503-22-bkppfb.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=549&fit=crop&dpr=1 754w, https://images.theconversation.com/files/524201/original/file-20230503-22-bkppfb.PNG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=549&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/524201/original/file-20230503-22-bkppfb.PNG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=549&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption"><em>Tineola bisselliella</em> larvae living it up on a scrap of sweater in the lab.</span>
<span class="attribution"><span class="source">Isabel Novick</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>These moths can eat hair, skin and feathers, all of which comprise a protein called keratin. Keratin – the main ingredient in nails, hoofs and horns – is <a href="https://doi.org/10.1371/journal.pone.0202608">notoriously tough to digest</a>. Biologists still aren’t sure how clothes moths can metabolize keratin, and this is something I aim to address in my research. One study posits that they harbor a <a href="https://doi.org/10.3390/microorganisms8091415">microorganism in their gut</a> that uses digestive enzymes to break down keratin for them.</p>
<p>However mysterious the process may be, their nutritional needs can be met with as little as a hairball and <a href="http://publichealth.lacounty.gov/eh/docs/safety/managing-clothes-moth-infestations.pdf">some vitamin B</a>, which they can glean from sweat, pee and food stains. Not only that, but research suggests these moths somehow <a href="https://agris.fao.org/agris-search/search.do?recordID=US201301122326">produce water as a byproduct of digesting keratin</a>, so they can happily survive within the dry recesses of your home.</p>
<p>Incredibly, webbing clothes moths can safely digest poisonous heavy metals like <a href="https://doi.org/10.1071/BI9510049">arsenic, mercury and lead</a>. They can easily <a href="https://doi.org/10.1016/j.jspr.2005.08.004">chew through soft plastics and metabolize synthetic fabrics</a>. They have been known to feast on <a href="https://www.researchgate.net/publication/292321410_Forensic_entomology_applied_to_a_mummified_corpse">mummified human remains</a> and have even been a recognizable pest long enough to be <a href="https://bible.knowing-jesus.com/topics/Moths">mentioned in the Bible</a>. They are so economically destructive that by the 1990s they were causing up to <a href="https://www.wiley.com/en-us/Introduction+to+Insect+Pest+Management%2C+3rd+Edition-p-9780471589570">US$1 billion in damage per year in the U.S. alone</a>.</p>
<p>This pest insect, over time, has hitchhiked all over the world. It can now be found from Australia to Chile, from Nigeria to Canada. The current hypothesis is that these moths originated in Africa and expanded their range by <a href="https://doi.org/10.1016/j.jspr.2005.08.004">hitchhiking on 19th-century ships</a>. </p>
<p>Scientists consider webbing clothes moths synanthropes: organisms that benefit from, and <a href="https://davidrousefaicp.com/synanthropic-species-why-are-they-important-to-our-future/">have adapted to, human spaces</a>, much like pigeons or bedbugs. They have taken this to an extreme and are now <a href="https://doi.org/10.4081/jear.2011.83">mostly found indoors</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/524673/original/file-20230505-27-dokyrv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="color drawing of an insect with long antennae and folded wings" src="https://images.theconversation.com/files/524673/original/file-20230505-27-dokyrv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/524673/original/file-20230505-27-dokyrv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=456&fit=crop&dpr=1 600w, https://images.theconversation.com/files/524673/original/file-20230505-27-dokyrv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=456&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/524673/original/file-20230505-27-dokyrv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=456&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/524673/original/file-20230505-27-dokyrv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=572&fit=crop&dpr=1 754w, https://images.theconversation.com/files/524673/original/file-20230505-27-dokyrv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=572&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/524673/original/file-20230505-27-dokyrv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=572&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">These moths aren’t particularly pleasing to the human eye.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/carpet-moth-tineidae-artwork-by-steve-roberts-news-photo/492779087">Steve Roberts/De Agostini Picture Library via Getty Images</a></span>
</figcaption>
</figure>
<p>Researchers are still not sure what evolutionary adaptations have allowed these moths to colonize, and ultimately depend upon, human environments. However, it seems likely to me that their global domination is associated with their diet. Webbing clothes moths are known as <a href="https://doi.org/10.4081/jear.2011.83">facultative keratinophages</a>, which means they can choose to eat and digest keratin, but it’s not a required part of their diet. This kind of nutritional flexibility is common to other well-known synanthropic species – is there anything a raccoon won’t eat? – and may be fundamental to the moths’ successful global dispersal.</p>
<h2>Moth genes from around the world</h2>
<p>To study the differences between populations of webbing clothes moths around the world, I am analyzing a type of genomic data made from sequencing “<a href="https://doi.org/10.1093/sysbio/sys004">ultraconserved elements</a>.” This technique targets specific genes that all moth species share, called orthologs, and compares the variable genetic regions on both sides of the conserved sequence. This data tells researchers like me how distantly related the clothes moths in, say, Australia are to clothes moths in Hawaii.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/524647/original/file-20230505-25-gz6i5l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="about a dozen small dead moths stuck to sticky cardboard" src="https://images.theconversation.com/files/524647/original/file-20230505-25-gz6i5l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/524647/original/file-20230505-25-gz6i5l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=619&fit=crop&dpr=1 600w, https://images.theconversation.com/files/524647/original/file-20230505-25-gz6i5l.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=619&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/524647/original/file-20230505-25-gz6i5l.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=619&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/524647/original/file-20230505-25-gz6i5l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=778&fit=crop&dpr=1 754w, https://images.theconversation.com/files/524647/original/file-20230505-25-gz6i5l.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=778&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/524647/original/file-20230505-25-gz6i5l.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=778&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">This trap came back with plenty of moths that unwittingly donated themselves to science.</span>
<span class="attribution"><span class="source">Isabel Novick</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>To that end, I’ve spent the past two years internationally shipping pheromone-baited moth traps to interested volunteers. They set up the traps in their closets or storage rooms. After two months, I ask whether they’ve caught anything, request a photo of the trap and have them ship it back to me.</p>
<p>People generally want to help because they hope my research will yield better <a href="https://ipm.ucanr.edu/PMG/PESTNOTES/pn7435.html">methods of moth eradication</a>. Ultimately, it may, but I’m primarily interested in appreciating these organisms from an evolutionary perspective.</p>
<p>So far, I have received over 600 moths. But many of my correspondents don’t catch anything, or catch the wrong thing. Sometimes the trap gets thrown out with the trash. Sometimes I send a trap and never hear from the recipient again. It can be a frustrating process. I end up spending hundreds of dollars and sifting through hundreds of moths, most of them other tineids or pantry moths, looking for the flash of dusty golden wings. </p>
<p>I spend a lot of my time in the lab extracting moth DNA and a lot of time on my computer analyzing it. Ideally, this research will yield a more comprehensive picture of how moths in this family are related to one another, and clarify whether clothes moths from around the world are actually the species we think they are. If these moths are experiencing sexual isolation, we might be using the wrong methods to control them depending on their location. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/524202/original/file-20230503-1364-y4rm31.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="pale moth with dark eye" src="https://images.theconversation.com/files/524202/original/file-20230503-1364-y4rm31.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/524202/original/file-20230503-1364-y4rm31.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=277&fit=crop&dpr=1 600w, https://images.theconversation.com/files/524202/original/file-20230503-1364-y4rm31.PNG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=277&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/524202/original/file-20230503-1364-y4rm31.PNG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=277&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/524202/original/file-20230503-1364-y4rm31.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=348&fit=crop&dpr=1 754w, https://images.theconversation.com/files/524202/original/file-20230503-1364-y4rm31.PNG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=348&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/524202/original/file-20230503-1364-y4rm31.PNG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=348&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption"><em>Tineola bisselliella</em> moth, ready for its close-up through the microscope.</span>
<span class="attribution"><span class="source">Isabel Novick</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<h2>Appreciation for a pest</h2>
<p>Even though clothes moths can destroy your wardrobe or devour priceless objects like taxidermy, oriental carpets and upholstered furniture <a href="https://www.latimes.com/entertainment-arts/story/2021-04-22/getty-museum-covid-closure-moth-remediation">in museum collections</a>, I can’t help but admire them.</p>
<p>They are not intentionally pests; they are innovative, cunning and endlessly capable. Their ability to capitalize on unfilled niches has allowed them to spread far and wide throughout homes everywhere. They’re not chomping through your drapes with malicious intent; they’re operating exactly as they evolved to, in a way that has worked to their advantage for thousands of years. The reasons people dislike them – being persistent, destructive and difficult to eradicate, not to mention dull-colored – are the reasons they’ve been able to survive and thrive so successfully for so long.</p>
<p>I gently urge you to consider their efficiency and determination as a sort of evolutionary elegance. How incredible is it for something to have evolved to eat the inedible, to occupy the uninhabitable and to overcome every evolutionary obstacle in its way? Of course, that doesn’t mean their damage can’t be devastating, or that battling these moths doesn’t stink. But, from an evolutionary standpoint, the webbing clothes moth should inspire wonder instead of disgust, awe instead of frustration, and instead of exasperation, admiration.</p><img src="https://counter.theconversation.com/content/200048/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>I used to work at the Museum of Science, Boston</span></em></p>An appreciation for the moths that chomp holes in your clothes. They eat the inedible, occupy the uninhabitable and overcome every evolutionary obstacle in their way.Isabel Novick, Doctoral Candidate in Ecology, Behavior and Evolution, Boston UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2006542023-03-30T15:04:11Z2023-03-30T15:04:11ZWhat the complicated social lives of wasps can teach us about the evolution of animal societies<figure><img src="https://images.theconversation.com/files/518429/original/file-20230330-17-8lsr1v.jpg?ixlib=rb-1.1.0&rect=0%2C6%2C4098%2C2717&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The yellowjacket wasp has a reputation as a British picnic invader</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/wasp-macro-wide-open-mandibles-640529671">Denis Vesely/Shutterstock</a></span></figcaption></figure><p>It’s spring in England. The daffodils are in full bloom. A queen yellowjacket (<em>Vespula</em>) wasp emerges from your loft, dopey with hibernation and hungry for nectar. She starts to build a paper nest in which to raise a family. It will be a large family. But for now, she works alone. </p>
<p>Wasps are <a href="https://resjournals.onlinelibrary.wiley.com/doi/10.1111/een.12676">poorly studied</a> compared with other social insects, like bees and ants. But wasp societies are a fascinating example of a social insect (an insect that lives in a group) because their societies are so varied. Comparing their genetic makeup with other social insects helps bolster our <a href="https://pubmed.ncbi.nlm.nih.gov/26051561/">understanding of how animal societies evolved</a>. </p>
<p>My team sequenced the genes involved with social behaviour from <a href="https://www.nature.com/articles/s41467-023-36456-6">nine wasp species</a> to explore what makes a queen (or a worker). What we found challenges a popular scientific view about the molecular machinery that makes insect societies tick.</p>
<p>The shared division of labour, in the form of queen and worker castes, is the secret to success for all social insects. Castes evolved independently at least <a href="https://pubmed.ncbi.nlm.nih.gov/18511689/">eight times in Hymenoptera</a> – that’s bees, wasps and ants.</p>
<p>When her first brood hatches, the yellowjacket queen becomes a dedicated egg producer. Her worker offspring will take over extending the nest and foraging for prey to feed to the baby siblings. The workers will never be queens. Like tissues in your body, the queen and her workers divide the chores of the society between them: seamless cooperation between two forms of wasp.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/518243/original/file-20230329-1905-g7mqmv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/518243/original/file-20230329-1905-g7mqmv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=596&fit=crop&dpr=1 600w, https://images.theconversation.com/files/518243/original/file-20230329-1905-g7mqmv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=596&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/518243/original/file-20230329-1905-g7mqmv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=596&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/518243/original/file-20230329-1905-g7mqmv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=749&fit=crop&dpr=1 754w, https://images.theconversation.com/files/518243/original/file-20230329-1905-g7mqmv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=749&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/518243/original/file-20230329-1905-g7mqmv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=749&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Vespula vulgaris - common yellowjacket wasp. Spring queens build a nest alone. CC BY SA Frank Hornig.</span>
</figcaption>
</figure>
<h2>Socialising that comes with a sting</h2>
<p>By contrast, in other societies, like <em>Metapolybia</em> wasps in Trinidad, many queens and workers will search together for a new place to nest. The swarm selects a tree trunk and starts to build a papery nest that resembles a cow pat. </p>
<p>For now, there are many queens and many workers, but after a few weeks of growing the nest, a single queen reigns. Scientists don’t know how the queen is chosen but those who don’t make the final cut act as workers. Young <em>Metapolybia</em> workers are “totipotent” which means they can become queen <a href="https://www.science.org/doi/10.1126/science.200.4340.441">if the resident queen dies</a>. Older workers, however, have been through a form of insect “menopause” and can’t reproduce. </p>
<p>Other wasp societies are simpler. Take the <em>Polistes</em> paper wasps that live along the banks of the Panama Canal, where their nests hang like the soles of old shoes from trees, bridges and houses. Dozens of chestnut bodies sit on a nest: every female is totipotent, but only one wasp is queen at any one time. When the queen dies, the hierarchy breaks down and they <a href="https://www.cell.com/cell-systems/fulltext/S2405-4712(22)00315-5?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2405471222003155%3Fshowall%3Dtrue">fight viciously to replace her</a>. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/518251/original/file-20230329-24-m0gwn7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/518251/original/file-20230329-24-m0gwn7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=1046&fit=crop&dpr=1 600w, https://images.theconversation.com/files/518251/original/file-20230329-24-m0gwn7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=1046&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/518251/original/file-20230329-24-m0gwn7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=1046&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/518251/original/file-20230329-24-m0gwn7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1314&fit=crop&dpr=1 754w, https://images.theconversation.com/files/518251/original/file-20230329-24-m0gwn7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1314&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/518251/original/file-20230329-24-m0gwn7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1314&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Polistes canadensis nest, from Panama.</span>
</figcaption>
</figure>
<p>Thanks to advances in molecular biology, we now know queens and workers in insect societies are different expressions of the same genome (the entire set of DNA instructions found within a cell). The physiological and behavioural differences that allow castes to perform their specialist tasks are because the colony’s shared genes are activated differently. Hundreds of genes separate queens from workers in the honeybee. Some of the same genes separate castes in fire ants, bumblebees and paper wasps. There’s a <a href="https://www.annualreviews.org/doi/abs/10.1146/annurev-ento-031616-035601">shared social toolkit</a>.</p>
<p>At least scientists thought so.</p>
<h2>What we learned</h2>
<p>One problem is that comparing data across different species, methods and labs is tricky. You’re not comparing like for like. Researchers tend to focus on a <a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243088">few popular species</a> and different labs may generate results in <a href="https://www.nature.com/articles/s41576-019-0150-2">different ways</a>. It’s difficult to compare data sets because it is easy to fall into the trap of cherrypicking the genes we expect to see in a social toolkit for the “usual suspects”.</p>
<p>My team took a look at the bigger picture. We sequenced the genes <a href="https://www.nature.com/articles/s41467-023-36456-6">activated in the brains</a> from nine genera (biological classes) of social wasps from around the globe, including representatives of some of the simplest and most complex societies known in the animal kingdom. We focused on brains because differences in brain genome activation shape behaviour like foraging, mating and nest building, and physiology, such as egg production. We also used the same sampling and sequencing techniques across all our species.</p>
<p>We used artificial intelligence (AI) because computers are better at spotting patterns than humans as they can process more complex patterns faster. They are also more objective. The computer was trained to identify castes. We then asked it to classify samples as queens or workers, based on the patterns of which genes were activated in a sample. </p>
<p>If the social toolkit hypothesis was correct, we should have seen swathes of shared activation profiles for queens and workers across all species. </p>
<p>The machines found some evidence for this. From over 5,000 orthologous genes (genes shared by all species), the computer correctly identified queens and workers for seven of the nine species. Intriguingly, the results showed queens are characterised by more inactive genes compared with workers, perhaps because workers perform a wider repertoire of tasks, while queens are egg-laying specialists.</p>
<p>But the complexity of a society also matters. Our AI methods showed the shared molecular toolkit provides the basic recipe that is enough for simpler societies. But additional molecular processes are needed for the more complex societies. Especially those that are superorganisms, like the yellowjacket wasps.</p>
<p>The machinery used to create a totipotent paper wasp worker isn’t necessarily the same as that required to make a lifetime committed sterile yellowjacket worker. </p>
<p>Our results showed the molecular toolkit for social life is more complex than previously thought. My team’s study found that the type of colony influences the way evolution tinkers with the building blocks of life to create societies.</p>
<p>Life history complicates this even further. Whether a species builds new nests alone (like the yellowjacket) or with a swarm of other queens and workers (like <em>Metapolybia</em>) can influence the social toolkit too. </p>
<p>Limiting our scientific focus to a few popular species has given us a blinkered view of evolution’s great experiment: societies. The transition from simple groups (like paper wasps) to the highly complex machines of the superorganisms (like the yellowjackets) may require a fundamental shift in molecular machinery. Like all of life’s greatest challenges, innovation is the key to success.</p><img src="https://counter.theconversation.com/content/200654/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Seirian Sumner receives funding from the Natural Environment Research Council (NERC). She is an employee of University College London. Her book Endless Forms: Why We Should Love Wasps, is published by William Collins in paperback on March 30th 2023. It reveals the full diversity of wasps, solitary and social, and aims to help readers appreciate the many benefits that wasps offer to ourselves and our planet.</span></em></p>Think your social life is complicated? Consider the wasp.Seirian Sumner, Professor of Behavioural Ecology, UCLLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1898102022-12-09T16:16:44Z2022-12-09T16:16:44ZPicky eater? Research shows it could be in your DNA<figure><img src="https://images.theconversation.com/files/482335/original/file-20220901-4639-94389p.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C5406%2C3834&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Ever wondered why people can't agree on what foods taste good? </span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/image-pretty-young-woman-sitting-kitchen-579904396">Shift Drive/Shutterstock </a></span></figcaption></figure><p>In the last <a href="https://www.weforum.org/agenda/2016/11/this-map-shows-the-rapid-increase-in-global-obesity/">40 years</a> obesity has been constantly rising. This has happened despite the popularity of all kind of diets ranging from low carb, paleo or even <a href="https://www.menshealth.com/weight-loss/a19546608/ice-cream-diet-32-lb-weight-loss/">ice cream based</a>.</p>
<p>Many scientists believe this is because cheap junk food has filled supermarket shelves and <a href="https://www.sciencedirect.com/science/article/abs/pii/S0149763414003339?via%3Dihub">fast food takeaways</a>. This food is high in calories and other not so healthy ingredients such as saturated fats, simple sugars, and salt. But it’s designed to <a href="https://onlinelibrary.wiley.com/doi/10.1002/oby.22639">taste delicious</a>. Taste is a dealbreaker when it comes to deciding what to eat, diet plans or not. Yet our understanding of what makes food taste good is limited.</p>
<p><a href="https://www.nature.com/articles/s41467-022-30187-w">My team’s research</a> explored how genes and biological processes influence which foods we find irresistible. We partnered with <a href="https://www.ukbiobank.ac.uk/">UK biobank</a> to ask the participants in our study how much they liked 139 foods, rating them from one to nine on a questionnaire, with nine being the most delicious. UK biobank is a collection of almost 500,000 UK volunteers, who agreed to provide their personal information for scientific purposes. They were aged from 50 to 70 at the time of our study.</p>
<p>We sent the questionnaire by email and received close to 189,000 responses. The first step in our study was to analyse links between food people said they liked. For example if someone likes pears, can we expect them to also like apples and strawberries. We mapped the relationships between different foods.</p>
<figure class="align-center ">
<img alt="Many multi coloured spices and dried fruits on a black table" src="https://images.theconversation.com/files/482339/original/file-20220901-4342-r5kkzf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/482339/original/file-20220901-4342-r5kkzf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/482339/original/file-20220901-4342-r5kkzf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/482339/original/file-20220901-4342-r5kkzf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/482339/original/file-20220901-4342-r5kkzf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/482339/original/file-20220901-4342-r5kkzf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/482339/original/file-20220901-4342-r5kkzf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Some flavours are an acquired taste.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/many-multi-colored-spices-dried-fruits-1748223017">Gulcin Ragiboglu/Shutterstock</a></span>
</figcaption>
</figure>
<h2>Good taste</h2>
<p>We found food can be categorised in three groups: highly palatable foods which include meat, junk food and desserts; low calorie foods, mostly fruit and salad vegetables, but also oatmeal and honey; and acquired taste foods which are strong tasting foods children generally dislike but <a href="https://tobaccocontrol.bmj.com/content/25/Suppl_2/ii32">learn to enjoy</a> such as coffee, alcohol and spices.</p>
<p>The map revealed some surprises. Foods didn’t group by flavour type (such as sweet v savoury) but by how likeable they were. For example, a taste for fruit juices correlated more with preference for desserts rather than fruit. So fruit juice went in the highly palatable category rather than low calorie. Foods people think of as vegetables do not cluster together. The mild tasting ones such as tomatoes or courgette are in the low calorie group while the strong tasting ones, like bell peppers or onions, were in the acquired taste group. Also sweet drinks like sodas clustered closer to meat and deep fried foods despite their sweet flavour.</p>
<p>We then looked at which differences in people’s DNA could be linked to the types of food they relish. We identified 325 different genes, mostly in the brain, implicated in determining what we like to eat. When we looked at how much the three categories of foods correlated genetically between each other we found that the highly palatable foods had no correlation with the other two categories of foods. This suggests there are two biological processes. One regulates a weakness for highly pleasurable foods while another regulates the rest. </p>
<h2>What’s next</h2>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716899/">Twin studies</a> suggest food preference is 50% genes and 50% personal experience. The family environment plays a role in children’s food preferences but not in those of adults. The shift happens around adolescence. It is still not clear how a liking for different food matures in children as no one has carried out largescale longitudinal studies. My team would like to try and fill this gap in research next.</p>
<figure class="align-center ">
<img alt="Curly haired woman holds a scoop of ice cream" src="https://images.theconversation.com/files/482337/original/file-20220901-809-kp0mbh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/482337/original/file-20220901-809-kp0mbh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/482337/original/file-20220901-809-kp0mbh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/482337/original/file-20220901-809-kp0mbh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/482337/original/file-20220901-809-kp0mbh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/482337/original/file-20220901-809-kp0mbh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/482337/original/file-20220901-809-kp0mbh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The answer to why ice cream is irresistible could be in your genes.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/pleased-millennial-girl-curly-hair-bites-1779076454">Cast Of Thousands/Shutterstock</a></span>
</figcaption>
</figure>
<p>For our study we also used MRI brain scans to look in more detail at which areas of the brain correlated with the three food groups. We once again found that enjoyment of highly palatable foods was associated with a larger volume of brain areas involved in perceiving pleasure in food. The other two groups were associated with brain areas involved with sensory perception, identification and decision making. </p>
<p>These findings shed a new light on our understanding of people’s food choices. If you understand why you don’t like certain foods it may help you improve the way you cook or prepare them. For example many people do not like coriander as it “tastes soapy”. This is <a href="https://www.news-medical.net/health/The-Genetics-of-Corianders-Soapy-Taste.aspx#:%7E:text=Coriander%20also%20has%20some%20aldehydes,the%20soapy%20taste%20in%20coriander.">genetically determined</a>, giving some people a sensitivity to a <a href="https://www.nature.com/articles/nature.2012.11398">compound in coriander</a>. Cooking coriander instead of <a href="https://www.myrecipes.com/how-to/cooking-questions/why-cilantro-tastes-like-soap">eating it raw</a> reduces the soapy flavour. This is a simple example but it shows how a little preparation may make foods more acceptable. </p>
<p>Health professionals and schools could use the information on taste and people’s DNA to identify those more at risk of having unhealthy diet choices and help them with early targeted programmes. Pharmacological solutions could shift someone’s preference for different types by activating different parts of the brain or hormones. For example, high levels of a <a href="https://academic.oup.com/endo/article/160/5/1069/5364429?login=false">hormone called FGF21</a> can trigger a preference for savoury food, low levels can trigger a preference for sweeter food. It may be possible in the future to develop medicine that changes the foods you take pleasure in eating.</p><img src="https://counter.theconversation.com/content/189810/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Nicola Pirastu does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Our experiences of taste are so vivid and personal it can be hard to imagine how people can turn their nose up at your favourite comfort food. Research shows the explanation could be in your genes.Nicola Pirastu, Senior Manager Biostatistics Unit at Human Technopole and Honorary Fellow, The University of EdinburghLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1947802022-11-30T16:01:54Z2022-11-30T16:01:54ZAncient DNA from the teeth of 14th-century Ashkenazi Jews in Germany already included genetic variations common in modern Jews<figure><img src="https://images.theconversation.com/files/498055/original/file-20221129-11920-w79ymf.jpg?ixlib=rb-1.1.0&rect=38%2C31%2C2036%2C1406&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Partial layout of the graves discovered during the excavation at the medieval Jewish cemetery of Erfurt.</span> <span class="attribution"><span class="source">Thuringian State Office for Heritage Management and Archaeology/Karin Sczech + Katharina Bielefeld</span></span></figcaption></figure><p>About two-thirds of Jews today – or about 10 million people – are <a href="https://en.wikipedia.org/wiki/Ashkenazi_Jews">Ashkenazi</a>, referring to a recent origin from Eastern and Central Europe. They reside mostly in the United States and Israel. Ashkenazi Jews carry a particularly high burden of <a href="https://www.jewishgeneticdiseases.org/jewish-genetic-diseases/">disease-causing genetic mutations</a>, such as those in the <a href="https://www.cdc.gov/cancer/breast/young_women/bringyourbrave/hereditary_breast_cancer/jewish_women_brca.htm">BRCA1</a> gene associated with an increased risk of breast and ovarian cancer.</p>
<p>This genetic burden suggests that the population was shaped by what geneticists call a <a href="https://evolution.berkeley.edu/bottlenecks-and-founder-effects/">founder event or a bottleneck</a>. In other words, a small number of foremothers and forefathers contributed much of the modern gene pool. As the population grew and the descendants of these founders had many children, disease mutations that were carried by the few founders became widespread.</p>
<p>One of the most striking features of Ashkenazi Jews today is <a href="https://doi.org/10.1093/molbev/msr133">how genetically homogeneous</a> they are, with almost no discernable differences in ancestry between Ashkenazi Jews across the world. Were Ashkenazi Jews equally similar to each other in the past? What were their origins? To what extent was the gene pool shaped by intermarriage with non-Jews?</p>
<p><a href="https://doi.org/10.1146/annurev-genom-083117-021749">New technology</a> has made it practical to economically sequence whole genomes from skeletal remains. <a href="https://scarmilab.org">We</a> <a href="https://reich.hms.harvard.edu">and</a> 30 colleagues mostly from Israel, Germany and the U.S. investigated these questions by <a href="http://dx.doi.org/10.1016/j.cell.2022.11.002">sequencing the centuries-old remains of Ashkenazi Jews</a> from the medieval Jewish community of Erfurt, Germany.</p>
<h2>Sequencing DNA from a medieval cemetery</h2>
<p>Previous studies of genomes of Ashkenazi Jews living today made it clear that the <a href="https://doi.org/10.1016/j.ajhg.2012.08.030">founder event occurred in medieval times</a>. But the earlier geographic origins of the Ashkenazi ancestors are poorly understood.</p>
<p>The first historical records of Ashkenazi Jews are from the Rhineland in Western Germany in the 10th century. In the hundreds of years that followed, an increasing proportion lived in Eastern Europe. Despite periodic persecution, the <a href="https://www.bjpa.org/content/upload/bjpa/dell/DellaPergola%20Some%20Fundamentals.pdf">number of Ashkenazi Jews grew</a> and peaked at more than 10 million in the mid-20th century, before about <a href="https://www.worldcat.org/title/33397139">six million Jews were murdered in the Holocaust</a>.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/498052/original/file-20221129-22-c2soy0.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="four story medieval building with excavated dirt in foreground" src="https://images.theconversation.com/files/498052/original/file-20221129-22-c2soy0.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/498052/original/file-20221129-22-c2soy0.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=901&fit=crop&dpr=1 600w, https://images.theconversation.com/files/498052/original/file-20221129-22-c2soy0.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=901&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/498052/original/file-20221129-22-c2soy0.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=901&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/498052/original/file-20221129-22-c2soy0.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1132&fit=crop&dpr=1 754w, https://images.theconversation.com/files/498052/original/file-20221129-22-c2soy0.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1132&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/498052/original/file-20221129-22-c2soy0.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1132&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Archaeologists worked to recover medieval remains from a graveyard. The granary building is in the background.</span>
<span class="attribution"><span class="source">Thuringian State Office for Heritage Management and Archaeology/Martin Sowa</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>The <a href="https://juedisches-leben.erfurt.de/jl/en/middle-ages/index.html">medieval Ashkenazi Jewish community of Erfurt, Germany</a> existed between the late 11th century and the mid-15th century. After a gap following a 1349 massacre, the Erfurt Jewish community became one of the largest in Germany – in fact, one of the <a href="https://juedisches-leben.erfurt.de/jl/en/middle-ages/old_synagogue/index.html">oldest intact Jewish synagogues</a> in Central Europe is in Erfurt – but Jews were expelled in 1454. After that, the city built a granary on top of the Jewish cemetery.</p>
<p>In 2013, the granary was converted into a parking garage. Prior to construction, the state led a rescue excavation that uncovered 47 graves, most of which we sampled for DNA before the skeletons were reburied in the 19th-century Jewish cemetery.</p>
<p>Our study required review from the local Jewish community, because traditional Jewish law prohibits disturbing the dead under most circumstances. But <a href="https://din.org.il/2021/09/11/%d7%93%d7%92%d7%99%d7%9e%d7%95%d7%aa-%d7%93%d7%a0%d7%90-%d7%9e%d7%a9%d7%9c%d7%93%d7%99%d7%9d-%d7%a2%d7%aa%d7%99%d7%a7%d7%99%d7%9d-%d7%a1%d7%95%d7%92%d7%99%d7%95%d7%aa-%d7%94%d7%9c%d7%9b/">recent rabbinical scholarship</a> suggested that ancient DNA research is permissible if scientists use loose teeth from already excavated remains. We followed this approach with the aim of being <a href="https://doi.org/10.1038/s41586-021-04008-x">sensitive to community perspectives</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/497959/original/file-20221129-12-puyzlr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="tooth next to ruler and labelled plastic bag" src="https://images.theconversation.com/files/497959/original/file-20221129-12-puyzlr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/497959/original/file-20221129-12-puyzlr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=468&fit=crop&dpr=1 600w, https://images.theconversation.com/files/497959/original/file-20221129-12-puyzlr.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=468&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/497959/original/file-20221129-12-puyzlr.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=468&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/497959/original/file-20221129-12-puyzlr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=589&fit=crop&dpr=1 754w, https://images.theconversation.com/files/497959/original/file-20221129-12-puyzlr.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=589&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/497959/original/file-20221129-12-puyzlr.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=589&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">In accordance with rabbinical ruling, researchers collected DNA from teeth that were already loose in the remains of people who lived during the 1300s.</span>
<span class="attribution"><span class="source">David Reich/Harvard Medical School</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<h2>Today’s population is a blend of past groups</h2>
<p>We sequenced 33 individuals who lived in the 14th century. Among them were two families: a mother and two children, and a father, who had likely been killed by a sword blow to the head, and his daughter.</p>
<p>Our first question was: Do medieval Erfurt Jews and modern Ashkenazi Jews belong to the same genetic population? On average, yes. There has been almost no incorporation of genes from non-Jewish European populations over the last 600 years. </p>
<p>But the biggest surprise was that Erfurt Jews were noticeably more diverse than modern Ashkenazi Jews.</p>
<p>Some medieval individuals had greater Middle Eastern ancestry; they were genetically most similar to modern Ashkenazi Jews with origins in France and Germany.</p>
<p>Others had greater Eastern European ancestry, consistent with historical evidence that a number of people living in Erfurt between 1350 and 1400 had surnames indicating origins in the East, as well as Slavic given names.</p>
<p>The two groups – those with more Middle Eastern or more Slavic origins – also had distinct levels of <a href="https://en.wikipedia.org/wiki/%CE%9418O">oxygen isotopes</a> in their teeth, indicating they used different water sources in childhood, and thus, at least one of the groups must have included migrants. </p>
<p>Nevertheless, individuals from both groups were buried side by side, suggesting no social segregation.</p>
<p>Non-genetic research suggested that in the Middle Ages, Ashkenazi Jews were <a href="https://global.oup.com/academic/product/origins-of-yiddish-dialects-9780198739319">culturally divided into two major groups</a>. Western Jews lived in the Rhineland, where Ashkenazi Jews first settled. They may correspond to the Erfurt group with the greater Middle Eastern ancestry. Eastern Jews, from eastern Germany, Austria, Bohemia, Moravia and Silesia, may correspond to the Erfurt group with the greater Eastern European ancestry.</p>
<p>Erfurt was at the geographic boundary between the two medieval Jewish communities, and in the 14th century, it was likely a home to Jews belonging to both. This may explain our detection of two genetically distinguishable groups in one place.</p>
<p>Modern Ashkenazi Jews don’t show the medieval genetic heterogeneity. Instead, their genomes look like a nearly even mixture of the two Erfurt groups. Our genetic results fit with <a href="https://global.oup.com/academic/product/origins-of-yiddish-dialects-9780198739319">studies of names, dialects and religious rites</a>, which suggest that the Western and Eastern groups eventually merged and formed a single Ashkenazi culture.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/498061/original/file-20221129-18-uoe4mi.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="a man kneeling on pad on dirt works on something buried in the ground" src="https://images.theconversation.com/files/498061/original/file-20221129-18-uoe4mi.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/498061/original/file-20221129-18-uoe4mi.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=375&fit=crop&dpr=1 600w, https://images.theconversation.com/files/498061/original/file-20221129-18-uoe4mi.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=375&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/498061/original/file-20221129-18-uoe4mi.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=375&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/498061/original/file-20221129-18-uoe4mi.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=472&fit=crop&dpr=1 754w, https://images.theconversation.com/files/498061/original/file-20221129-18-uoe4mi.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=472&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/498061/original/file-20221129-18-uoe4mi.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=472&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">In advance of construction, archaeologists carefully excavated medieval remains so they could be respectfully reburied in a 19th century cemetery.</span>
<span class="attribution"><span class="source">Thuringian State Office for Heritage Management and Archaeology/Ronny Krause</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<h2>A founder event left its genetic mark</h2>
<p>Our next question was whether Erfurt Jews show signs of the founder event so evident in the genes of modern Ashkenazi Jews.</p>
<p>They do. A stretch of genetic material called <a href="https://www.nature.com/scitable/topicpage/mtdna-and-mitochondrial-diseases-903/">mitochondrial DNA</a> is inherited only from mothers. Different people around the world today carry subtly different variations of it. One variant of mitochondrial DNA is found in 20% of modern Ashkenazi Jews and is nearly absent in non-Jewish populations. We identified it in 35% of the Erfurt individuals.</p>
<p>In other words, a third of the people we sampled from the graveyard descended, via their maternal line, from a single woman. That so many people share the same ancestral mother implies that the population must have been extremely small in the centuries before.</p>
<p>In the Erfurt individuals, we also found mutations common in Ashkenazi Jews today but extremely rare elsewhere, including 16 disease-causing mutations, one of them in the well-known BRCA1 gene. Another research group sequenced the genomes of <a href="https://doi.org/10.1016/j.cub.2022.08.036">six Ashkenazi Jews from 12th-century Norwich, England</a> and identified other disease mutations that are also still seen in Ashkenazi genomes today.</p>
<p>What was most striking about the founder event was how strongly the Erfurt Jews were affected. We estimate that the degree of relatedness of <a href="https://doi.org/10.1016/j.ajhg.2012.08.030">modern Ashkenazi Jewish genomes to each other</a> is about what would be expected if they descended from a population that had been persistently small throughout the second half of the Middle Ages. How small? We calculated that a core of only 1,000-2,000 reproducing people during this time would be responsible for most descendants today.</p>
<p>When we repeated a similar calculation using the Erfurt data, we encountered a surprise. Based on the medieval DNA, our estimate of the size of the founding population was about 3-fold smaller, only around 500 people. </p>
<p>How could it be that we were detecting the same founder event – responsible for the same disease-causing mutations in the Erfurt and in the modern Ashkenazi Jewish communities – and yet its impact on the Erfurt Jews was larger? </p>
<p>To address that, we proposed there were additional medieval Ashkenazi communities that inherited much less DNA from the core group of reproducing people we identified for Erfurt. We don’t yet know who these communities were, but our modeling suggests that they must have existed and later mixed with Erfurt-like communities, averaging together to form today’s Ashkenazi Jews.</p>
<p>So sometime after the 14th century, genetic barriers between Ashkenazi Jewish communities must have broken down, and the archipelago of scattered early Ashkenazi Jewish populations collapsed into the homogeneous group seen today. This was accompanied by extremely rapid population growth, which then continued for centuries. The Ashkenazi Jewish community, which had originally been demographically peripheral in the Jewish world, with its center of gravity around the Mediterranean and the Middle East, eventually became the largest world population of Jews.</p>
<h2>A template for future studies</h2>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/497962/original/file-20221129-16-tumege.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="view of an old stone building through a stone arch" src="https://images.theconversation.com/files/497962/original/file-20221129-16-tumege.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/497962/original/file-20221129-16-tumege.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=688&fit=crop&dpr=1 600w, https://images.theconversation.com/files/497962/original/file-20221129-16-tumege.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=688&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/497962/original/file-20221129-16-tumege.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=688&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/497962/original/file-20221129-16-tumege.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=865&fit=crop&dpr=1 754w, https://images.theconversation.com/files/497962/original/file-20221129-16-tumege.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=865&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/497962/original/file-20221129-16-tumege.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=865&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The Old Synagogue of the medieval Jewish community of Erfurt is now a museum documenting past Jewish life in Erfurt.</span>
<span class="attribution"><span class="source">Stadt Erfurt Marcel Krummrich</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>Erfurt and Norwich are just two locations. A richer picture of medieval Ashkenazi Jewish history will require sampling additional sites. How Ashkenazi Jews relate to Sephardi Jews and the many other living Jewish communities, and how all of these communities relate to Roman-period Judeans, are mysteries that ancient DNA research may also one day address. Any such research would need to take into account modern community sensitivities, and we think our work in Erfurt is a good model.</p>
<p>More broadly, this work provides a template for how ancient DNA, even from individuals who lived relatively recently, can reveal aspects of history that are otherwise invisible. By carrying out such studies, scholars can help reveal the roots of modern groups, enriching people’s understanding of themselves and each other.</p><img src="https://counter.theconversation.com/content/194780/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Shai Carmi received funding for this study from the Israel Science Foundation and the United States-Israel Binational Science Foundation. He is a paid consultant at MyHeritage.</span></em></p><p class="fine-print"><em><span>David Reich receives funding for his research from the US National Institutes of Health, the Allen Discovery Center program (a Paul G. Allen Frontiers Group advised program of the Paul G. Allen Family Foundation), the John Templeton Foundation; a private gift from Jean-François Clin, and the Howard Hughes Medical Institute.</span></em></p>A German town needed to relocate a medieval graveyard to build a parking garage. A positive side effect: Scientists got to sequence the DNA of Ashkenazi Jews who lived more than 600 years ago.Shai Carmi, Associate Professor of Population and Statistical Genetics, Hebrew University of JerusalemDavid Reich, Professor of Genetics and of Human Evolutionary Biology, Harvard UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1938072022-11-30T13:39:31Z2022-11-30T13:39:31ZPregnancy is a genetic battlefield – how conflicts of interest pit mom’s and dad’s genes against each other<figure><img src="https://images.theconversation.com/files/497774/original/file-20221128-20372-q68nv3.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2059%2C1454&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Paternal and maternal genes drive fetal development in different directions.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/hacking-baby-embryo-decoding-the-dna-of-royalty-free-illustration/1125420175">Valentina Kruchinina/iStock via Getty Images</a></span></figcaption></figure><p>Baby showers. Babymoons. Baby-arrival parties. There are many opportunities to celebrate the 40-week transition to parenthood. Often, these celebrations implicitly assume that pregnancy is cooperative and mutually beneficial to both the parent and the fetus. But this belief obscures a more interesting truth about pregnancy – the mother and the fetus may not be peacefully coexisting in the same body at all.</p>
<p>At the most fundamental level, there is a conflict between the interests of the parent and fetus. While this may sound like the beginning of a thriller, this <a href="https://doi.org/10.1086/418300">genetic conflict</a> is a normal part of pregnancy, leading to typical growth and development both during pregnancy and across an individual’s lifetime – something <a href="https://scholar.google.com/citations?user=YBPxHqkAAAAJ&hl=en&oi=ao">my research</a> focuses on. </p>
<p>However, even though genetic conflict is normal during pregnancy, it can play a role in pregnancy complications and developmental disorders when left unchecked.</p>
<h2>What is genetic conflict?</h2>
<p>Pregnancy is generally thought of as a period when a new individual is created from a unified blend of genes from their parents. But this is not quite right. </p>
<p>The genes a fetus gets from each parent carry slightly different instructions for development. This means there are contrasting and sometimes conflicting blueprints for how to build the new individual. Conflict over <a href="https://doi.org/10.1016/0168-9525(91)90230-N">which blueprint to follow</a> for fetal growth and development is the essence of the genetic conflict that occurs during pregnancy.</p>
<p>Moms have to use their bodies to help the fetus grow during pregnancy while dads don’t. This means that the genes the fetus inherits from mom have to not only provide for the current fetus, but also try to keep mom alive and healthy and make sure there are resources left over for a potential future pregnancy. These reserves include both biological resources like glucose, protein, iron and calcium, as well as the time and energy needed to help her children after birth as they grow and develop.</p>
<p>Dad’s genes don’t have this same pressure because they don’t use their bodies to help the fetus grow during pregnancy. A dad’s genes, then, don’t need to ensure that anyone other than the current fetus thrives.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/F_ssj7-8rYg?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Pregnancy transforms every organ in the body.</span></figcaption>
</figure>
<p>To better understand this situation, pretend that all of the resources a mom can give her children come in the form of a <a href="https://cir.nii.ac.jp/crid/1570854174915527168">milkshake</a>. Once the milkshake runs out, mom has nothing left to give her children. Maternal genes, therefore, want each child to drink only as much as they need to grow and develop. This ensures that the milkshake can be “shared” across all current and future children. </p>
<p>Paternal genes, on the other hand, have no such guarantee of representation in this mother’s other children – the father of the current child may not be the father of the mother’s potential future children. This lack of guaranteed genetic representation means there is no pressure on the father to “share” the milkshake. The best strategy when it comes to paternal genes, then, is for the fetus to drink as much of the milkshake as they can.</p>
<p>These two strategies play a figurative game of tug of war throughout pregnancy. Both sides are trying to pull fetal development slightly more toward their side. Paternal genes encourage the fetus to grow and develop quickly and take more resources, while maternal genes encourage the fetus to grow and use only what’s necessary for proper development. Conflict over how deeply the <a href="https://doi.org/10.1016/0168-9525(91)90230-N">embryo implants</a> in the uterus and how quickly the <a href="https://doi.org/10.1016/j.placenta.2012.05.002">placenta</a> and <a href="https://doi.org/10.1016/j.placenta.2005.07.004">fetus</a> grow are just a few areas where researchers have documented this tug of war during pregnancy.</p>
<p>The milkshake problem helps researchers determine where to look for genetic conflict by simplifying where trade-offs may take place during pregnancy. Because fetal growth is at the heart of genetic conflict, researchers have focused on processes where conflict over resource transfers from mother to fetus can be observed. These investigations have found that the placenta, a fetal organ responsible for all resource transfers during pregnancy, is <a href="https://www.hup.harvard.edu/catalog.php?isbn=9780674027220">dominated by paternally-expressed genes</a>. It releases paternally-derived <a href="https://doi.org/10.1038/ng0593-98">insulin-like growth factors</a> that make mom less sensitive to her own insulin and hormones that <a href="https://doi.org/10.1093/humrep/16.1.13">increase maternal blood pressure</a>, both of which ultimately increase the amount of resources the fetus can use to grow during pregnancy but have the potential to harm the mother’s health.</p>
<h2>Genetic conflict and pregnancy complications</h2>
<p>If genetic conflict goes uncontrolled, it can cause <a href="https://doi.org/10.1086/418300">pregnancy complications</a> for the mother and <a href="https://doi.org/10.1002/ajhb.10150">developmental disorders</a> for the child. In fact, there is a growing consensus among researchers that some of the most well-known pregnancy complications like <a href="https://doi.org/10.1126/science.1111726">preeclampsia</a>, <a href="https://doi.org/10.1007/978-3-319-19650-3_3044">gestational diabetes</a>, <a href="https://doi.org/10.1016/j.semcdb.2022.01.007">miscarriages</a> and <a href="https://doi.org/10.1093/aje/kwp325">preterm births</a> may best be explained by unchecked genetic conflict.</p>
<p>Despite the potential role that genetic conflict plays in pregnancy complications, current medical treatments are reactive rather than proactive. A pregnant person must <a href="https://www.mayoclinic.org/diseases-conditions/preeclampsia/diagnosis-treatment/drc-20355751">show signs of experiencing complications</a> before medical interventions and treatments can take place. </p>
<p>Knowing how unchecked genetic conflict contributes to pregnancy complications could provide researchers another way to develop treatments that are proactive and, ideally, preventive. However, there are currently no treatments for pregnancy complications that consider genetic conflict. Though <a href="https://doi.org/10.2337%2Fdb19-0798">gestational diabetes</a> can be attributed to underlying genetic conflict, a pregnant person must present with elevated blood sugar levels before doctors can treat underlying conflict over insulin production and blood sugar.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/PO2Z2afWib8?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Pregnancy during the COVID-19 pandemic has been challenging for many.</span></figcaption>
</figure>
<p>The experiences of pregnant people during the COVID-19 pandemic provide an example of why more research on genetic conflict is needed. During the pandemic, doctors saw both a dramatic decrease in the number of <a href="http://dx.doi.org/10.1136/archdischild-2020-319990">preterm births</a> as well as an increase in the number of <a href="https://doi.org/10.1001/jama.2020.12746">stillbirths and miscarriages</a>. Both types of complications are influenced by genetic conflict, but the reasons behind these opposing trends are unclear.</p>
<p>As a woman who was pregnant early in the pandemic, my pregnancy was scary and stressful, spent at home away from the pressures of “normal” life. More research on the complex process of pregnancy and genetic conflict’s role in complications could help researchers better understand how the changes brought by the pandemic produced such wildly different pregnancy outcomes.</p><img src="https://counter.theconversation.com/content/193807/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jessica D. Ayers does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Genetic conflict may play a role in pregnancy complications, such as preeclampsia and gestational diabetes, as well as developmental disorders.Jessica D. Ayers, Assistant Professor of Psychological Science, Boise State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1947932022-11-21T13:15:49Z2022-11-21T13:15:49ZPeople don’t mate randomly – but the flawed assumption that they do is an essential part of many studies linking genes to diseases and traits<figure><img src="https://images.theconversation.com/files/496010/original/file-20221117-25-slwoe3.jpg?ixlib=rb-1.1.0&rect=110%2C96%2C4690%2C2134&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Statistical pitfalls in GWAS can result in misleading conclusions about whether some traits (like long horns or spotted skin, in the case of dinosaurs) are genetically linked.</span> <span class="attribution"><span class="source">@meanymoo</span>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span></figcaption></figure><p>The idea that <a href="https://doi.org/10.1002/0471667196.ess0209.pub2">correlation does not imply causation</a> is a fundamental caveat in epidemiological research. A classic example involves a hypothetical link between ice cream sales and drownings – instead of increased ice cream consumption causing more people to drown, it’s plausible that a third variable, summer weather, is driving up an appetite for ice cream and swimming, and hence opportunities to drown.</p>
<p>But what about correlations involving genes? How can researchers be sure that a particular trait or disease is truly genetically linked, and not caused by something else?</p>
<p>We are <a href="https://www.richardborder.com">statistical</a> <a href="https://scholar.google.com/citations?user=SPXgieEAAAAJ&hl=en">geneticists</a> who study the genetic and nongenetic factors that influence human variation. In our <a href="https://www.science.org/doi/10.1126/science.abo2059">recently published research</a>, we found that the genetic links between traits found in many studies might not be connected by genes at all. Instead, many are a result of how humans mate.</p>
<h2>Genome-wide association studies try to link genes to traits</h2>
<p>Because the genes you inherit from your parents remain unchanged throughout your life, with rare exception, it makes sense to assume that there is a causal relationship between certain traits you have and your genetics.</p>
<p>This logic is the basis for <a href="https://www.genome.gov/about-genomics/fact-sheets/Genome-Wide-Association-Studies-Fact-Sheet">genome-wide association studies, or GWAS</a>. These studies collect DNA from many people to identify positions in the genome that might be correlated with a trait of interest. For example, if you have certain forms of the <a href="https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet"><em>BRCA1</em> and <em>BRCA2</em> genes</a>, you may have an increased risk for certain types of cancer.</p>
<p>Similarly, there may be gene variants that play a role in whether or not someone has schizophrenia. The hope is to learn something about the complex mechanisms that link variation at the molecular level to individual differences. With a clearer understanding of the genetic basis of different traits, scientists would be better able to determine risk factors for related diseases. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/sOP8WacfBM8?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">GWAS studies seek to find genetic associations between individual traits.</span></figcaption>
</figure>
<p>Researchers have run <a href="https://doi.org/10.1093/nar/gky1120">thousands of GWAS to date</a>, identifying genetic variants associated with myriad diseases and disease-related traits. In many instances, researchers have identified genetic variants that affect more than one trait. This form of biological overlap, in which the same genes are thought to influence several apparently unrelated traits, is known as <a href="https://doi.org/10.1186/s13073-016-0332-x">pleiotropy</a>. For example, certain variants of the <a href="https://medlineplus.gov/genetics/gene/pah"><em>PAH</em> gene</a> can have <a href="https://medlineplus.gov/genetics/condition/phenylketonuria/">several distinct effects</a>, including altering skin pigmentation and causing seizures.</p>
<p>One way scientists assess pleiotropy is through <a href="https://doi.org/10.1038/ng.3604">genetic correlation analysis</a>. Here, geneticists investigate whether the genes associated with a given trait are associated with other traits or diseases by statistically analyzing large samples of genetic data. Over the past decade, genetic correlation analysis has become the primary method for assessing potential pleiotropy across fields as diverse as <a href="https://doi.org/10.1038/ng.3406">internal medicine</a>, <a href="https://www.thessgac.org">social science</a> and <a href="https://doi.org/10.1017/s0033291717002318">psychiatry</a>. </p>
<p>Scientists use the findings from genetic correlation analyses to figure out the potential shared causes of these traits. For instance, if <a href="https://doi.org/10.1126/science.aap8757">genes associated with bipolar disorders</a> also predict anxiety disorders, perhaps the two conditions may partially involve some of the same neural circuits or respond to similar treatments.</p>
<h2>Assortative mating and genetic correlation</h2>
<p>However, just because a gene is correlated with two or more traits doesn’t necessarily mean it causes them.</p>
<p>Virtually all the statistical methods researchers commonly use to assess genetic correlations <a href="https://doi.org/10.1046/j.1439-0388.2002.00356.x">assume that mating is random</a>. That is, they assume that potential mating partners decide who they will have children with based on a roll of the dice. In reality, many factors likely influence who mates with whom. The simplest example of this is geography – people living in different parts of the world are less likely to end up together than people living nearby.</p>
<p>We wanted to find out how much the assumption of random mating affects the accuracy of genetic correlation analyses. In particular, we focused on the potential confounding effects of <a href="https://doi.org/10.1038/s41562-018-0476-3">assortative mating</a>, or how people tend to mate with those who share similar characteristics with them. Assortative mating is a widely documented phenomenon seen across a broad array of traits, interests, measures and social factors, including <a href="https://doi.org/10.1002/ajhb.22917">height</a>, <a href="https://doi.org/10.2307/2095670">education</a> and <a href="https://doi.org/10.1016/j.biopsych.2019.06.025">psychiatric conditions</a>.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/bK85aZPR3UY?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Humans do not mate randomly – rather, people tend to gravitate toward certain traits.</span></figcaption>
</figure>
<p>In <a href="https://doi.org/10.1126/science.abo2059">our study</a> we examined cross-trait assortative mating, whereby people with one trait (for example, being tall) tend to mate with people with a completely different trait (for example, being wealthy). From our database of 413,980 mate pairs in the U.K. and Denmark, we found evidence of cross-trait assortative mating for many traits – for instance, an individual’s time spent in formal schooling was correlated not only with their mate’s educational attainment, but also with many other characteristics, including height, smoking behaviors and risk for different diseases.</p>
<p>We found that taking into consideration the similarities across mates could strongly predict which traits would be considered genetically linked. In other words, just based on how many characteristics a pair of mates shared, we could identify around 75% of the presumed genetic links between these traits – all without sampling any DNA.</p>
<h2>Genetic correlation does not imply causation</h2>
<p>Cross-trait assortative mating shapes the genome. If people with one heritable trait tend to mate with people with another heritable trait, then these two distinct characteristics will become genetically correlated to each other in subsequent generations. This will happen regardless of whether or not these traits are truly genetically linked to each other.</p>
<p>Cross-trait assortative mating means that the genes you inherit from one parent will be correlated with those you inherit from the other. How people mate is not random, violating the key assumption behind genetic correlation analyses. This inflates the genetic association between traits that aren’t truly linked together by genes.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/495756/original/file-20221116-21-hyom6p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Illustration of dinosaurs with and without long horns or spiked backs." src="https://images.theconversation.com/files/495756/original/file-20221116-21-hyom6p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/495756/original/file-20221116-21-hyom6p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=424&fit=crop&dpr=1 600w, https://images.theconversation.com/files/495756/original/file-20221116-21-hyom6p.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=424&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/495756/original/file-20221116-21-hyom6p.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=424&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/495756/original/file-20221116-21-hyom6p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=533&fit=crop&dpr=1 754w, https://images.theconversation.com/files/495756/original/file-20221116-21-hyom6p.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=533&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/495756/original/file-20221116-21-hyom6p.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=533&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">If dinosaurs with long horns preferentially mate with dinosaurs with spiked backs, genes for both of these traits can become associated with each other in subsequent generations even though the same gene doesn’t code for them.</span>
<span class="attribution"><span class="source">Aaqilah M</span>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
</figure>
<p>Recent studies corroborate our findings. Earlier this year, researchers computed genetic correlations using a method that examines the association between the <a href="https://doi.org/10.1038/s41588-022-01062-7">traits and genes of siblings</a>. The genetic links between traits influenced by cross-trait assortative mating were substantially weakened.</p>
<p>But without accounting for cross-trait assortative mating, using genetic correlation estimates to study the biological pathways causing disease can be misleading. Genes that affect only one trait will appear to influence multiple different conditions. For example, a genetic test designed to assess the risk for one disease may incorrectly detect vulnerability for a broad number of unrelated conditions.</p>
<p>The ability to measure variation across individuals at the genetic and molecular level is truly a feat of modern science. However, genetic epidemiology is still an observational enterprise, subject to the same caveats and challenges facing other forms of nonexperimental research. Though our findings don’t discount all genetic epidemiology research, understanding what genetic studies are truly measuring will be essential to translate research findings into new ways to treat and assess disease.</p><img src="https://counter.theconversation.com/content/194793/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Richard Border receives funding from the National Institutes of Health.</span></em></p><p class="fine-print"><em><span>Noah Zaitlen receives funding from the NIH, NSF, DoD, and CZI. </span></em></p>People don’t randomly select who they have children with. And that means an underlying assumption in research that tries to link particular genes to certain diseases or traits is wrong.Richard Border, Postdoctoral Researcher in Statistical Genetics, University of California, Los AngelesNoah Zaitlen, Professor of Neurology and Human Genetics, University of California, Los AngelesLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1865802022-11-09T16:24:18Z2022-11-09T16:24:18ZThe study of evolution is fracturing – and that may be a good thing<figure><img src="https://images.theconversation.com/files/492997/original/file-20221102-42436-qk7an2.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C13274%2C8264&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/amazing-moment-monarch-butterfly-pupae-cocoons-1938757099">Darkdiamond67/Shutterstock</a></span></figcaption></figure><p>How will life on Earth and the ecosystems that support it adapt to climate change? Which species will go extinct – or evolve into something new? How will microbes develop further resistance to antibiotics? </p>
<p>These kinds of questions, which are of fundamental importance to our way of life, are all a focus for researchers who study evolution and will prove increasingly important as the planet heats up. </p>
<p>But finding the answers isn’t the only challenge facing evolutionary biology. Charles Darwin’s theories might be over 150 years old but major questions about how evolution works are far from settled. </p>
<p>Evolutionary biology is now undergoing one of the most intense debates it has had for more than a generation. And how this debate plays out could have a significant impact on the future of this scientific field.</p>
<p>Some biologists and philosophers claim that <a href="https://www.theguardian.com/science/2022/jun/28/do-we-need-a-new-theory-of-evolution">evolutionary biology needs reform</a>, arguing that traditional explanations for how organisms change through time that scientists have assumed <a href="https://www.oxfordbibliographies.com/view/document/obo-9780199941728/obo-9780199941728-0115.xml">since the 1930s</a> are holding back the assimilation of novel findings</p>
<p>Contemporary evolutionary biology, a vocal minority <a href="https://www.nature.com/articles/514161a">argue</a>, is incomplete. The dominant and traditional view of the field is too preoccupied with how the genes in a population change over time. This neglects, these critics argue, how individual organisms shape their environments and adjust themselves during their lifetimes to survive and reproduce.</p>
<p>Some go so far as to say that evolutionary theory itself is <a href="https://www.independent.co.ug/evolutionary-theorys-welcome-crisis/">in crisis</a> and must be <a href="https://journals.biologists.com/jeb/article/218/1/7/13568/Evolution-beyond-neo-Darwinism-a-new-conceptual">replaced</a> with something new. </p>
<p>Not all biologists <a href="https://royalsocietypublishing.org/doi/full/10.1098/rspb.2016.2864?etoc=">are convinced</a>. Some argue that repeated calls for reform are mistaken and can actually <a href="https://link.springer.com/article/10.1007/s10539-016-9557-8">hinder progress</a>.</p>
<figure class="align-center ">
<img alt="Three petri dishes arranged side by side." src="https://images.theconversation.com/files/493000/original/file-20221102-47877-k7qr16.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/493000/original/file-20221102-47877-k7qr16.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=240&fit=crop&dpr=1 600w, https://images.theconversation.com/files/493000/original/file-20221102-47877-k7qr16.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=240&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/493000/original/file-20221102-47877-k7qr16.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=240&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/493000/original/file-20221102-47877-k7qr16.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=302&fit=crop&dpr=1 754w, https://images.theconversation.com/files/493000/original/file-20221102-47877-k7qr16.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=302&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/493000/original/file-20221102-47877-k7qr16.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=302&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">How microbes develop resistance to antibiotics is evolution in action.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/antimicrobial-resistance-susceptibility-tests-by-diffusion-2035530317">MD_style/Shutterstock</a></span>
</figcaption>
</figure>
<h2>Modern evolutionary theory</h2>
<p>The version of evolutionary biology that is still largely taught in schools has its origin in <a href="https://ecoevorxiv.org/gjf8s/">the modern synthesis</a>. This fused Gregor Mendel’s theory that organisms inherit discrete particles (what we now call genes) with Charles Darwin’s theory of natural selection. Darwin suggested that environmental conditions weed out heritable traits which are unhelpful and promote those which offer organisms an advantage.</p>
<p>The modern synthesis aimed to unify biology, but it was dominated by a few subfields, particularly genetics and paleontology, and focused on how populations change their genetic make-up over time. From this perspective, organisms are objects and the raw material for natural selection. </p>
<p>Notably, the modern synthesis did not incorporate all fields. The study of how embryos develop and how organisms interact with each other and their environment (ecology) were largely left out.</p>
<p>Organisms are not, critics of the modern synthesis argue, passive objects of natural selection. Instead, they say, organisms are agents that <a href="https://www.jstor.org/stable/j.ctt24hqpd">change those environments</a>. </p>
<p>A famous example is the beaver, which builds dams to survive and reproduce, changing its surroundings in the process. This tinkering in turn influences natural selection on itself and other species, thereby changing the beaver’s long-term evolution.</p>
<p>Organisms also inherit <a href="https://royalsocietypublishing.org/doi/10.1098/rspb.2015.1019">more than DNA</a>. This challenges the modern synthesis’s assumption that traits an organism acquires during a single lifetime cannot be passed down. </p>
<p>There is cultural transmission: <a href="https://www.nature.com/articles/ncomms11693">killer whales</a> teach their children and grandchildren hunting skills and food preferences. Songbirds transfer nutrients to new generations <a href="https://www.nature.com/articles/s42003-018-0247-8">in eggs</a> just as humans give their offspring antibodies through breast milk. Some biologists say that these endowments can revitalise the study of evolutionary biology, diverting our attention from strict genetic inheritance.</p>
<figure class="align-center ">
<img alt="A killer whale calf surfaces between two large dorsal fins." src="https://images.theconversation.com/files/493001/original/file-20221102-22-f16d5x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/493001/original/file-20221102-22-f16d5x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/493001/original/file-20221102-22-f16d5x.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/493001/original/file-20221102-22-f16d5x.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/493001/original/file-20221102-22-f16d5x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/493001/original/file-20221102-22-f16d5x.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/493001/original/file-20221102-22-f16d5x.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The transmission of information between generations can influence a species’ evolution.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/killer-whale-calf-surfaces-surrounded-by-97761248">Monika Wieland Shields/Shutterstock</a></span>
</figcaption>
</figure>
<h2>Diversity is a strength</h2>
<p>As an evolutionary ecologist with an interest in how organisms adapt to their environments, I am not as worried as some that the current version of evolutionary biology is incomplete. Neither am I particularly concerned about the limitations of population genetics. </p>
<p>Evolution can clearly be described as changing gene frequencies between generations. But this does not mean that population genetics is the only useful way to study evolution.</p>
<p>Biologists might disagree on what constitutes <a href="https://www.pnas.org/doi/10.1073/pnas.0702207104">an evolutionary process</a>, with natural selection and random changes in DNA being the two best studied processes. Evolutionary processes are not the only interesting aspect of evolution, though. </p>
<p>Evolutionary outcomes and the products of evolution – organisms and how they develop – also keep biologists busy. We have come to understand more about how genes and environments interact to shape the development of organisms. These insights from <a href="https://www.naturalhistorymag.com/features/061488/the-origins-of-form">evolutionary developmental biology</a> have clearly enriched our field. </p>
<p>That evolutionary biology is increasingly fractured does not worry me either, as long as we recognise that a plurality of approaches is not a weakness, but a strength. If physicists cannot agree upon a <a href="https://science.jrank.org/pages/3095/Grand-Unified-Theory.html">grand unified theory</a> of the universe, why should biologists expect to agree on one beyond what we have already achieved? After all, organisms are much more complex than physical particles and processes.</p>
<p>To take another example from physics, light can be viewed either as a particle or a wave. This <a href="https://www.britannica.com/science/wave-particle-duality">duality</a> reflects how a single descriptor is not enough to fully describe the complex phenomenon of light. </p>
<p>If this works for physicists, why could evolutionary biologists not also use multiple ways of studying a process as complex as evolution, and things as complex as organisms? Why can we not see organisms as either agents capable of modifying their environments or objects subject to natural selection, depending on the context? These are two valuable and complementary perspectives.</p>
<figure class="align-center ">
<img alt="A red dragonfly resting on a plant frond." src="https://images.theconversation.com/files/493051/original/file-20221102-26750-z6zxo3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/493051/original/file-20221102-26750-z6zxo3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=460&fit=crop&dpr=1 600w, https://images.theconversation.com/files/493051/original/file-20221102-26750-z6zxo3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=460&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/493051/original/file-20221102-26750-z6zxo3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=460&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/493051/original/file-20221102-26750-z6zxo3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=578&fit=crop&dpr=1 754w, https://images.theconversation.com/files/493051/original/file-20221102-26750-z6zxo3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=578&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/493051/original/file-20221102-26750-z6zxo3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=578&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Organisms influence – and are influenced by – natural selection.</span>
<span class="attribution"><span class="source">Erik Svensson</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>Evolutionary biology today is a messy patchwork of <a href="https://link.springer.com/article/10.1007/s10539-016-9557-8">several loosely connected subfields</a>. This reflects the enormous diversity of phenomena that we study and the many interests of biologists. </p>
<p>We are united in accepting that natural selection on inheritance and random factors have jointly shaped organisms – but not by much more. Maintaining a coherent overview, either the modern synthesis or some extension to it, seems increasingly hopeless. </p>
<p>Giving up the search for a grand unified evolutionary theory will not hurt our field, but rather, liberate us. It will enable biologists to think more freely about <a href="https://www.seanbcarroll.com/endless-forms-most-beautiful">the endless forms most beautiful</a> that are constantly evolving and will continue to do so.</p><img src="https://counter.theconversation.com/content/186580/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Erik Svensson receives funding from from the Swedish Research Council (VR; grant no. 2020-03123). </span></em></p>There is more to evolution than the genes species inherit.Erik Svensson, Professor (Evolutionary Ecology Unit, Department of Biology), Lund UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1938192022-11-07T12:34:36Z2022-11-07T12:34:36ZEpilepsy: gene therapy technique targeting overactive brain cells shows promise in treating drug-resistant form of the condition<figure><img src="https://images.theconversation.com/files/493789/original/file-20221107-13-i4n7qr.jpg?ixlib=rb-1.1.0&rect=26%2C0%2C3500%2C1996&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Epileptic seizures are caused by brain cells becoming overactive.
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/neuronal-network-electrical-activity-neuron-cells-1691666992">MattLphotography/ Shutterstock</a></span></figcaption></figure><p>Something like <a href="https://www.who.int/news-room/fact-sheets/detail/epilepsy">50 million people worldwide</a> have epilepsy. While the majority of these people are able to use medications to manage and prevent their seizures, around one-third don’t respond well to these treatments. In such cases, the only option available to bring seizures under control is to <a href="https://epilepsysociety.org.uk/about-epilepsy/treatment/epilepsy-and-brain-surgery">remove the part of the brain</a> where seizures arise. But this procedure is extremely risky.</p>
<p>Since epileptic seizures are caused by excessive activity of brain cells (neurons) in specific parts of the brain, being able to target these neurons and turn them off could very well prevent seizures from happening.</p>
<p>Using an innovative new gene therapy approach we have developed, we were able to show in cell and animal models that it is possible to <a href="https://www.science.org/doi/epdf/10.1126/science.abq6656">specifically target the neurons</a> that cause epileptic seizures. This subsequently prevented them from becoming overactive and causing seizures in the future. </p>
<p>This discovery not only has major implications for treating drug-resistant epilepsy, but there’s a chance it may also be used to treat other neurological conditions caused by overactive neurons, including Parkinson’s disease and migraines.</p>
<h2>Gene therapy</h2>
<p>Gene therapy works by directly altering a person’s genes in order to treat a disease or condition. There are a few different ways of doing this.</p>
<p><a href="https://www.jneurosci.org/content/early/2019/02/12/JNEUROSCI.1143-18.2019?versioned=true">Previous studies</a> that have used gene therapy to treat epilepsy in animal models have done this by using a virus that has been altered in the lab so it’s no longer harmful. Researchers would inject the virus into the brain region where seizures occur. The virus would then implant stretches of DNA into the cells, effectively modulating the way they worked – <a href="https://www.nature.com/articles/s41591-018-0103-x">making them less active</a> and preventing seizures.</p>
<p>While this technique is far less invasive than brain surgery, the problem with the method is that it affects all the neurons in the brain region – not just those causing the seizures. It also permanently alters the properties of the cells that take up the virally delivered DNA, which can permanently modify brain function. </p>
<p>But our innovative new gene therapy tool has shown it’s possible to alter only the brain cells that cause seizures, leaving nearby healthy neurons unaffected. We were able to do this by taking advantage of how gene expression is normally regulated.</p>
<figure class="align-center ">
<img alt="An image of multiple DNA strands." src="https://images.theconversation.com/files/493795/original/file-20221107-3705-r3aoea.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/493795/original/file-20221107-3705-r3aoea.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/493795/original/file-20221107-3705-r3aoea.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/493795/original/file-20221107-3705-r3aoea.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/493795/original/file-20221107-3705-r3aoea.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/493795/original/file-20221107-3705-r3aoea.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/493795/original/file-20221107-3705-r3aoea.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Our new gene therapy tool targeted the body’s promoters.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/dna-molecule-macro-blue-string-on-775854724">SynthEx/ Shutterstock</a></span>
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<h2>The role of promoters</h2>
<p>The 20,000 or so genes we have in our body each contain instructions to make different proteins and molecules. These genes are typically under the control of neighbouring stretches of DNA, called promoters. These determine whether and how much of a particular protein is made. Different cells express different proteins depending on which promoters are active or inactive.</p>
<p>There’s also a special type of promoter (called “activity-dependent” promoters) that will only switch on in response to biochemical signals made by neurons when they fire intensely – such as during a seizure. We took advantage of these activity-dependent promoters, creating a gene therapy that senses and turns down the excitability of neurons that cause seizures. We did this by coupling activity-dependent promoters to DNA sequences that contain proteins which calm down neurons.</p>
<p>We initially tested the gene therapy tool in neurons grown in a dish, and then in mice that had drug-resistant epilepsy. We also tested this technique in lab-grown human “mini brains”. </p>
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Read more:
<a href="https://theconversation.com/scientists-grow-brain-tissue-with-different-regions-in-lab-17560">Scientists grow brain tissue with different regions in lab</a>
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<p>In each test, we were able to show this new gene therapy technique was effective in calming down the overactive neurons involved in seizures, while leaving healthy bystander cells unaffected.</p>
<p>Although it takes an hour or so to switch on – longer than the typical duration of a seizure – the new gene therapy is highly effective in preventing subsequent seizures. It does this by automatically selecting which neurons to treat and switching them off. It’s also able to return neurons to their original state when brain activity returns to normal. If seizures occur again, the promoter is ready to switch on. </p>
<p>The treatment therefore only has to be given once, but has a lasting effect – possibly lifelong. Importantly, the treatment did not affect the performance of the mice in tests of memory and other normal behaviour (such as their anxiety levels, learning and mobility).</p>
<p>We are excited by the breakthrough, because it could in principle bring the prospect of gene therapy to a wide range of people with drug-resistant epilepsy. But before the therapy is ready to use with these patients, we will need to put it through a number of tests to verify that it can be scaled up to larger brains.</p><img src="https://counter.theconversation.com/content/193819/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Gabriele Lignani consults to/owns shares in a company that aims to bring epilepsy gene therapy to the clinic. He received funding from Epilepsy Research UK and Medical Research Council. </span></em></p><p class="fine-print"><em><span>Dimitri Kullmann consults to/owns shares in a company that aims to bring epilepsy gene therapy to the clinic. He received funding from the Wellcome Trust and the Medical Research Council.</span></em></p>This technique could also be applied to other conditions, such as Parkinson’s disease.Gabriele Lignani, Associate Professor, Clinical & Experimental Epilepsy, UCLDimitri Kullmann, Professor of Neurology, UCLLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1856542022-07-07T09:45:03Z2022-07-07T09:45:03ZThe human body has 37 trillion cells. If we can work out what they all do, the results could revolutionise healthcare<figure><img src="https://images.theconversation.com/files/472254/original/file-20220704-22-1y09ee.jpg?ixlib=rb-1.1.0&rect=95%2C15%2C1922%2C1201&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Priscilla Chan and Mark Zuckerberg with Moshe Biton (right) and Aviv Regev (left). The Chan Zuckerberg Initiative is one of the major funders of the Human Cell Atlas.</span> <span class="attribution"><span class="source">Chan Zuckerberg Initiative</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span></figcaption></figure><p>The average body contains about 37 trillion cells – and we are in the midst of a revolutionary quest to understand what they all do. Unravelling this requires the expertise of scientists from all different backgrounds – computer scientists, biologists, clinicians and mathematicians – as well as new technology and some pretty sophisticated algorithms. </p>
<p>Where once a primitive microscope, essentially little more than a magnifying glass, would reveal a new cell directly and viscerally – in the same way that <a href="https://377.medium.com/first-person-in-the-world-who-discovered-the-sperm-cells-6c91b17a8df5#:%7E:text=Sperm%20were%20unknown%20to%20science,filled%20with%20tiny%2C%20wiggling%20cells.">Antonie van Leeuwenhoek discovered sperm</a> in 1677 – today it is analysis on a computer screen which brings us such revelations. But it’s just as wonderful.</p>
<p>This type of research is hard in all sorts of ways – from the science itself to the sociology of large teams working on it – but the pay-off can be huge. It certainly was for a consortium of 29 scientists who set out to determine which types of cells make up the lining of the trachea, or windpipe – and stumbled upon a new type of cell that could transform our understanding and treatment of cystic fibrosis.</p>
<p>The first time the team – co-led by <a href="https://biology.mit.edu/profile/aviv-regev/">Aviv Regev</a> at the <a href="https://www.broadinstitute.org/about-us">Broad Institute</a> of MIT and Harvard – came across these cells, they were looking at an analysis of 300 cells in the trachea of mice. Three cells didn’t seem to correspond to anything that had been seen before. Had it been just two, they might have dismissed it as an outcome of noise in the data – but three strange cells warranted a closer look.</p>
<p>In lab banter, they became known as the “hot cells”. The scientists repeated the experiment several times, and it soon became clear they really had stumbled upon a new type of cell in the trachea.</p>
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<img alt="" src="https://images.theconversation.com/files/288776/original/file-20190820-170910-8bv1s7.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/288776/original/file-20190820-170910-8bv1s7.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/288776/original/file-20190820-170910-8bv1s7.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/288776/original/file-20190820-170910-8bv1s7.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/288776/original/file-20190820-170910-8bv1s7.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/288776/original/file-20190820-170910-8bv1s7.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/288776/original/file-20190820-170910-8bv1s7.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<p><strong><em>This story is part of Conversation Insights</em></strong>
<br><em>The Insights team generates <a href="https://theconversation.com/uk/topics/insights-series-71218">long-form journalism</a> and is working with academics from different backgrounds who have been engaged in projects to tackle societal and scientific challenges.</em></p>
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<p>As it turned out, another team from the US and Switzerland had independently found the same thing. The two teams learnt of each other’s work by chance at a seminar in 2017. “It was one of those beautiful moments in science,” recalled <a href="http://www.weizmann.ac.il/dept/irb/Biton/">Moshe Biton</a> from the Broad Institute team, “when two groups found the same results separately.”</p>
<p>Both groups confirmed that these new cells exist in the human airways as well as in mice and, after meeting up, agreed to publish their <a href="https://www.nature.com/articles/s41586-018-0394-6">two papers</a> <a href="https://www.nature.com/articles/s41586-018-0393-7">side-by-side</a>. These new cells had not been noticed before, simply because they are so rare – they make up around 1% of cells in the airway. But that doesn’t mean they’re unimportant. When the two teams looked in detail at what made these cells stand out, they came across something astonishing.</p>
<p>One of the genes active in these new-found trachea cells turned out to be CFTR – the “cystic fibrosis transmembrane conductance regulator” gene. This gave their work a whole other level of meaning because <a href="https://www.cff.org/research-clinical-trials/basics-cftr-protein">mutations in this gene cause cystic fibrosis</a>.</p>
<p>Exactly how this disease is caused by the inheritance of a dysfunctional version of the CFTR gene has been a mystery ever since the link was <a href="https://www.science.org/doi/10.1126/science.2772644">discovered in 1989</a>. Cystic fibrosis is a complex disease, usually beginning in childhood, with symptoms often including lung infections and difficulty breathing. There are treatments but no cure.</p>
<p>Now it seems possible that the key to understanding the cause could lie in working out what these newly discovered cells do, and what happens to these cells if the CFTR gene is defective. The research continues.</p>
<p>But already from this discovery, and other research using similar methods, there is the sense that our understanding of the body’s cells is being transformed by a piercing new combination of biology and computer science. And this is where even more game-changing discoveries are about to be made.</p>
<h2>The diversity of human cells</h2>
<p>Every one of the 37 trillion-or-so cells in your body is unique to some extent. Types of cell are determined by the particular proteins they contain – so only a red blood cell has haemoglobin, for example, and a <a href="https://www.ninds.nih.gov/health-information/patient-caregiver-education/brain-basics-life-and-death-neuron#:%7E:text=Neurons%20are%20information%20messengers.,rest%20of%20the%20nervous%20system.">neuron</a> contains different proteins from an <a href="https://www.cancer.gov/publications/dictionaries/cancer-terms/def/immune-cell">immune cell</a>. No two cells in the body contain exactly the same amounts of each protein.</p>
<p><a href="https://www.penguin.co.uk/books/431895/the-beautiful-cure-by-daniel-m-davis/9781784702212">The immune system is especially complex</a>. It comprises many types of cells categorised by their core function – T cells, B cells and so on. But there are also countless subtle variations of these T cells and B cells. We don’t even really know how many variants there are – but if we could understand what they all do, we would better understand the immune system. This in turn would enable us to design new medicines to help the immune system to, for example, better fight cancer. </p>
<figure class="align-center ">
<img alt="Image of a human cell using super-resolution microscope" src="https://images.theconversation.com/files/472258/original/file-20220704-19-xwkp0u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/472258/original/file-20220704-19-xwkp0u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=521&fit=crop&dpr=1 600w, https://images.theconversation.com/files/472258/original/file-20220704-19-xwkp0u.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=521&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/472258/original/file-20220704-19-xwkp0u.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=521&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/472258/original/file-20220704-19-xwkp0u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=655&fit=crop&dpr=1 754w, https://images.theconversation.com/files/472258/original/file-20220704-19-xwkp0u.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=655&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/472258/original/file-20220704-19-xwkp0u.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=655&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A human natural killer cell pictured using Stimulated Emission Depletion (STED) microscopy.</span>
<span class="attribution"><span class="source">Ashley Ambrose and Daniel M Davis</span>, <span class="license">Author provided</span></span>
</figcaption>
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<p>One kind of immune cell that my research team at Manchester University studies is called the <a href="https://www.immunology.org/public-information/bitesized-immunology/cells/natural-killer-cells">natural killer cell</a>. There are about a thousand of these immune cells in each drop of your blood, and they are especially good at detecting and killing other cells that have turned cancerous or have become infected with a virus. Again, not all natural killer cells are alike. <a href="https://pubmed.ncbi.nlm.nih.gov/24154599/">One analysis</a> has estimated that there are many thousands of variants of this immune cell in any one person.</p>
<p>In 2020, my research lab carried out <a href="https://ashpublications.org/bloodadvances/article/4/7/1388/454300/Diversity-of-peripheral-blood-human-NK-cells">an analysis</a> which suggested that variants of natural killer cells in blood could be organised into eight categories. While their different roles in the body aren’t yet fully understood, it’s likely that some are especially adept at attacking particular kinds of virus, others are better at detecting cancer, and so on.</p>
<p>Other types of immune cell can be even more varied. Evidently, our component cells are as diverse as the human beings they make up, and understanding how such complex populations of cells work together (in this case, to defend against disease) is a vital frontier.</p>
<h2>Using the language of algorithms</h2>
<p>To penetrate this complexity, the diversity of human cells must be translated into the language of algorithms.</p>
<p>Imagine a cell contains just two kinds of protein, X and Y. Every individual cell will have a specific amount of each of these two proteins. This can be represented as a point on a graph where the level of protein X becomes a position along the x-axis, and the level of protein Y its location along the y-axis.</p>
<p>One cell may contain a high amount of protein X and a little of protein Y (which can be revealed by a <a href="https://www.beckman.com/resources/videos/scientific/introduction-to-flow-cytometry">flow cytometer</a> showing that the cell stains with a high amount of one antibody and a low amount of another antibody). This cell can then be represented as a point placed far along the x-axis and a little way up the y-axis.</p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/472263/original/file-20220704-21-dtlrr8.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/472263/original/file-20220704-21-dtlrr8.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=570&fit=crop&dpr=1 600w, https://images.theconversation.com/files/472263/original/file-20220704-21-dtlrr8.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=570&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/472263/original/file-20220704-21-dtlrr8.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=570&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/472263/original/file-20220704-21-dtlrr8.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=716&fit=crop&dpr=1 754w, https://images.theconversation.com/files/472263/original/file-20220704-21-dtlrr8.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=716&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/472263/original/file-20220704-21-dtlrr8.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=716&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Illustration of cell identification process.</span>
<span class="attribution"><span class="source">Manon Chauvin via Wikimedia, modified</span>, <span class="license">Author provided</span></span>
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</figure>
<p>As each cell takes up a position on the graph, those with similar levels of the X and also the Y protein – likely to be the same type of cell – appear as a cluster of points. If thousands or millions of cells are plotted in this way, the number of discrete clusters that emerge tells us how many types of cells there are. Also, the number of points within a cluster tells us how many cells there are of that type.</p>
<p>The wonderful thing is that this form of analysis can reveal how many kinds of cells are present in, say, a sample of blood or a tumour biopsy, without being guided in any way about which cells we are expecting to find. This means that unexpected results can turn up. A cluster of data points might appear with unexpected properties – implicating the discovery a new kind of cell.</p>
<p>Of course, cells need more than two coordinates to describe them. In fact, over the last decade, a type of analysis – known as <a href="https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-017-0467-4">single-cell sequencing</a>– has been developed to measure the extent to which individual cells use each of the 20,000 human genes it contains.</p>
<p>Which ones out of all the 20,000 human genes a particular cell is using – called the cell’s <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/transcriptome">transcriptome</a> – can then be analysed to create a “map” of different cells. We can’t imagine cells represented on a graph with 20,000 axes, but a computer algorithm can handle this analysis in just the same way it would one with only two variables. Similar cells are positioned close together, while cells using very different sets of genes are far apart.</p>
<p><a href="https://www.nature.com/articles/s41598-020-74567-y">Algorithms</a> to do this are borrowed from other fields of science, such as those used in analysing social networks. Then we get to spend days, if not years, mining the output, deciphering what the map means: how many types of cells there are, what defines their differences, and what they do in the body? </p>
<p>Right now, this endeavour is happening on an unprecedented scale thanks to the <a href="https://www.humancellatlas.org/learn-more/">Human Cell Atlas consortium</a> – leading to all kinds of <a href="https://www.penguin.co.uk/books/439335/the-secret-body-by-davis-daniel-m/9781529110975">discoveries about the human body</a>.</p>
<h2>The Human Cell Atlas</h2>
<p>In October 2016, Regev and <a href="https://www.sanger.ac.uk/person/teichmann-sarah/">Sarah Teichmann</a> from the <a href="https://www.sanger.ac.uk/about/">Wellcome Sanger Institute</a> organised an event in London for around 100 world-leading scientists to discuss how to chart every cell in the human body. The elevator pitch was to assemble something like Google Maps for the body: “We know the countries and main cities, now we need to map the streets and buildings.”</p>
<p>A year later, they had drafted a specific plan – to first try to profile 100 million cells from different systems and organs, using different people around the globe. Thousands of scientists in over 70 countries from every inhabited content have joined the consortiu since – it is an especially diverse community, as it should be for such a huge global scientific endeavour.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/472261/original/file-20220704-19-wlwce0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Large gathering of scientists" src="https://images.theconversation.com/files/472261/original/file-20220704-19-wlwce0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/472261/original/file-20220704-19-wlwce0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=388&fit=crop&dpr=1 600w, https://images.theconversation.com/files/472261/original/file-20220704-19-wlwce0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=388&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/472261/original/file-20220704-19-wlwce0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=388&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/472261/original/file-20220704-19-wlwce0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=488&fit=crop&dpr=1 754w, https://images.theconversation.com/files/472261/original/file-20220704-19-wlwce0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=488&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/472261/original/file-20220704-19-wlwce0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=488&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">First meeting of the Human Cell Atlas team in London, 2016.</span>
<span class="attribution"><span class="source">Thomas Farnetti/Wellcome</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
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<p>In many ways, this bold new ambition is a direct descendant of the <a href="https://www.genome.gov/human-genome-project/What">Human Genome Project</a>. By sequencing all the human genes contained in each human cell, officially completed in April 2003, all sorts of genetic variations have been linked to increased susceptibility to a specific illness.</p>
<p>However, genetic diseases manifest in the specific cells where that gene is normally used. So, crucially, an analysis of genes alone isn’t enough – we also need to know where in the human body these disease-causing genes are being switched on.</p>
<p>The Human Cell Atlas is bridging this gap between abstract genetic codes and the physicality of the human body. We’ve already seen one example of how important this is – the discovery of the cystic fibrosis gene being used by a new, rare cell. Another example comes from what happens during pregnancy.</p>
<h2>Unlocking the secrets of pregnancy</h2>
<p>For many years, we have known that <a href="https://www.penguin.co.uk/books/182952/the-compatibility-gene-by-davis-daniel-m/9780141972527">the immune system is intimately linked with pregnancy</a>. For example, some combinations of immune system genes are slightly more frequent than would be expected by chance in couples who have had three or more miscarriages. While we don’t yet understand why this is, working it out might be medically important in resolving problems in pregnancy.</p>
<p>To tackle the issue, a consortium of scientists (co-led by Teichmann as part of the Human Cell Atlas project) analysed around 70,000 cells from the placenta and lining of the womb from women who had terminated their pregnancy at between six and 14 weeks.</p>
<p>The placenta is the organ where nutrients and gases pass back and forth between the mother and developing baby. It was once thought the mother’s immune system must be switched off in the lining of the womb where the placenta embeds, so that the placenta and foetus aren’t attacked for being “alien” (like an unmatched transplant) on account of half the foetus’s genes coming from the father. But this view turned out to be wrong – or too simple at the very least.</p>
<p>We now know, from a variety of experiments including this analysis, that in the womb, the activity of the mother’s immune cells is somewhat lessened, presumably to prevent an adverse reaction against cells from the foetus, but the immune system is not switched off. Instead, the immune cells we met earlier, natural killer cells, well known for killing infected cells or cancer cells, take on a completely different, more constructive job in the womb; helping build the placenta.</p>
<p>The scientists’ analysis of 70,000 cells <a href="https://www.nature.com/articles/s41586-018-0698-6">has also highlighted</a> that all sorts of other immune cells are also important in the construction of a placenta. What they all do, though, isn’t yet clear – this is at the edge of our knowledge.</p>
<figure class="align-center ">
<img alt="Scientist talking at meeting" src="https://images.theconversation.com/files/472281/original/file-20220704-21-v511u5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/472281/original/file-20220704-21-v511u5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=417&fit=crop&dpr=1 600w, https://images.theconversation.com/files/472281/original/file-20220704-21-v511u5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=417&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/472281/original/file-20220704-21-v511u5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=417&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/472281/original/file-20220704-21-v511u5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=523&fit=crop&dpr=1 754w, https://images.theconversation.com/files/472281/original/file-20220704-21-v511u5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=523&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/472281/original/file-20220704-21-v511u5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=523&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Muzlifah Haniffa at the Human Cell Atlas launch meeting in 2016.</span>
<span class="attribution"><span class="source">Thomas Farnetti/Wellcome</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
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</figure>
<p><a href="https://www.ncl.ac.uk/medical-sciences/people/profile/mahaniffa.html">Muzlifah “Muzz” Haniffa</a> is one of the three women who led this analysis. As a physician and scientist, she sees the body from two perspectives on an almost daily basis: as a computational analysis of cells on a screen, and as patients who walk through the door. Both as stones and the arch they make.</p>
<p>Right now, these two views don’t easily mesh. But in time, they will. In the future, Haniffa thinks the tools doctors use on a daily basis – such as a stethoscope to listen to a person’s lungs, or a simple blood count – will be replaced by instruments that profile our body’s cells. Algorithms will analyse the results, clarify the underlying problem, and predict the best treatment. Many other physicians agree with her – this is the coming future of healthcare.</p>
<h2>What this could mean for you</h2>
<p>Babies are now routinely born by IVF, organ transplants have become common, and overall cancer survival rates in the UK have roughly doubled in recent years – but all these achievements are nothing to what’s coming.</p>
<p>As I’ve written about in <a href="https://www.amazon.co.uk/Secret-Body-Science-Human-Changing/dp/1529110971/">The Secret Body</a>, progress in human biology is accelerating at an unprecedented rate – not only through the Human Cell Atlas but in many other areas too. Analysis of our genes presents a <a href="https://www.theguardian.com/books/2013/aug/08/compatibility-gene-daniel-davis-review">new understanding of how we differ</a>; the actions of brain cells give clues to how our minds work; new structures found inside our cells lead to new ideas for medicine; proteins and other molecules found to be circulating in our blood change our view of mental health.</p>
<p>Of course, all science has an ever-increasing impact on our lives, but nothing affects us as deeply or directly as new revelations about the human body. On the horizon now, from all this research, are entirely new ways of defining, screening and manipulating health.</p>
<p>We are already accustomed to the idea that our personal genetic information can be used to guide our health. But a quieter – almost secret – revolution is also under way and it may have an even bigger impact on the future of healthcare: deep analytics of the human body’s cells.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/472745/original/file-20220706-23-vv620k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/472745/original/file-20220706-23-vv620k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=329&fit=crop&dpr=1 600w, https://images.theconversation.com/files/472745/original/file-20220706-23-vv620k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=329&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/472745/original/file-20220706-23-vv620k.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=329&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/472745/original/file-20220706-23-vv620k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=414&fit=crop&dpr=1 754w, https://images.theconversation.com/files/472745/original/file-20220706-23-vv620k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=414&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/472745/original/file-20220706-23-vv620k.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=414&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">In the future a whole cloud of health information will be available to you, if you want to delve into it.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/genetic-research-biotech-science-concept-human-1084540790">Shutterstock</a></span>
</figcaption>
</figure>
<p>One day, a watch that can measure a few simple things about your body will be seen as a laughably primitive tool. In the future, maybe within ten years or so, a whole cloud of information will be available – including an analysis of your body’s cells – and you will have to decide how much you want to delve into it. This revolution in human biology will equip us individually with new powers – and we will each need to decide for ourselves if and when to deploy them.</p>
<p>You may, for example, one day visit your doctor with something abnormal on your skin – a rash, itch, or something else. The doctor may then take a small sample of your skin, or perhaps a blood sample, and from a complete cell-by-cell analysis of what’s there, be able to precisely diagnose the problem and know the best treatment. Indeed, some of this might even be automated. Further into the future, if the equipment needed to do this gets small and cheap enough, perhaps the analysis could be done by yourself at home.</p>
<p>Diseases will also be more frequently predicted before any symptoms are present at all. Of course, this is one of the most vital missions of science: to stop human disease before it even begins. For some illnesses, this has been achieved already – with vaccines, clean water and improved sanitation. Now, with the human body opening up to us through computational analysis of cells, genes and more, new ways of pre-empting disease are emerging. We are compelled to seize this new opportunity – yet in practice, there are challenges and unintended consequences to contend with.</p>
<p>Take a familiar example: the idea of the body-mass index, a value derived from a person’s weight and height. This is used to label us as underweight, normal weight, overweight or obese. It’s useful as it indicates an increased risk of health problems arising, such as type 2 diabetes, and steps can be taken to reduce the likelihood of this occurring. But the label itself can also trigger other sorts of problems relating to a person’s self-worth, and how society views obesity and human diversity.</p>
<h2>Difficult decisions about how you live</h2>
<p>Every one of us is susceptible to some disease or other, to some extent. So as science progresses and we learn more and more about ourselves, we will surely all find ourselves drowning in data about ourselves, awash with estimates and probabilities that play games with our mind and our identity, and require us to make difficult decisions about our health and how we live.</p>
<p>It seems feasible, for example, that the state of a person’s immune system, analysed in depth, could help predict the symptoms they are likely to have if infected with the Sars-CoV-2 virus, for example. Markers of immune activity might even correlate with a person’s mental health. One analysis concluded that particular pro-inflammatory secretions from immune cells (called cytokines) are found at higher levels in <a href="https://www.sciencedirect.com/science/article/pii/S088915911830789X?via%3Dihub">people who are depressed</a>.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/coronavirus-we-must-step-up-research-to-harness-immense-power-of-the-immune-system-138071">Coronavirus: we must step up research to harness immense power of the immune system</a>
</strong>
</em>
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<p>As we learn about the composition and status of the human body, this will inevitably establish new ways of assessing health. And it may very well help resolve problems in pregnancy too, as we’ve seen. But there are problems here too – if an analysis suggests a chance of a problem, say 50%, how would you act on this information if the medical intervention that could help has its own risks too?</p>
<p>There is seemingly no end to how the metric analysis of the human body will lead to important but complex new health decisions. <a href="https://www.nytimes.com/2013/05/14/opinion/my-medical-choice.html">Angelina Jolie</a> famously acted on genetic information when she had both of her breasts surgically removed in 2013, and later her ovaries and fallopian tubes, following a genetic test which established that she had inherited a particular variation in a gene known as BRCA1. Crucially, she had been given a very high – 87% – chance of developing breast cancer. In general, risks and probabilities about our health are much less clear than this.</p>
<p>So the question arises, how are we to act on all this new information? What if something has been identified that means your risk of developing an autoimmune disease or cancer is one in six in the next ten years? Would it be different if it was one in four? At what point would you decide to take medicine as a precaution, or undergo surgery, knowing that they also carry their own risks? And would this knowledge in itself make you feel ill? Would your identity be affected?</p>
<p>I don’t have the answers – but that’s the point. As this new science progresses, each of us will have to decide how much we really want to know about ourselves.</p>
<hr>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=112&fit=crop&dpr=1 600w, https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=112&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=112&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=140&fit=crop&dpr=1 754w, https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=140&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=140&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<p><em>For you: more from our <a href="https://theconversation.com/uk/topics/insights-series-71218?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=InsightsUK">Insights series</a>:</em></p>
<ul>
<li><p><em><a href="https://theconversation.com/the-inside-story-of-recovery-how-the-worlds-largest-covid-19-trial-transformed-treatment-and-what-it-could-do-for-other-diseases-184772?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=InsightsUK">The inside story of Recovery: how the world’s largest COVID-19 trial transformed treatment – and what it could do for other diseases
</a></em></p></li>
<li><p><em><a href="https://theconversation.com/chinas-covid-crisis-and-the-dilemma-facing-its-leaders-by-experts-who-have-monitored-it-since-the-wuhan-outbreak-182451?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=InsightsUK">China’s COVID crisis and the dilemma facing its leaders, by experts who have monitored it since the Wuhan outbreak</a></em></p></li>
<li><p><em><a href="https://theconversation.com/the-discovery-of-insulin-a-story-of-monstrous-egos-and-toxic-rivalries-172820?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=InsightsUK">The discovery of insulin: a story of monstrous egos and toxic rivalries
</a></em></p></li>
</ul>
<p><em>To hear about new Insights articles, join the hundreds of thousands of people who value The Conversation’s evidence-based news. <a href="https://theconversation.com/uk/newsletters/the-daily-newsletter-2?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=InsightsUK"><strong>Subscribe to our newsletter</strong></a>.</em></p><img src="https://counter.theconversation.com/content/185654/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>This article is an edited extract from Daniel M. Davis' new book The Secret Body (Vintage paperback, 2022). Davis is also the author of two previous books The Beautiful Cure and The Compatibility Gene. He receives research funding from The Medical Research Council, Cancer Research UK, Wellcome, GSK and Bristol Myers Squibb. He tweets at @dandavis101
</span></em></p>Pioneered by the Human Cell Atlas consortium, our understanding of the human body is about to be transformed – and with it, the way we treat and prevent diseaseDaniel M Davis, Professor of Immunology, University of ManchesterLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1832952022-05-30T16:46:12Z2022-05-30T16:46:12ZIVF: here’s how genetics may be affecting its success – new insights<figure><img src="https://images.theconversation.com/files/465972/original/file-20220530-12-6su25.jpg?ixlib=rb-1.1.0&rect=0%2C8%2C5615%2C3724&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The success rate of IVF still remains at around 30%.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/doctor-psychologist-filling-medical-patient-information-1016244031">fizkes/ Shutterstock</a></span></figcaption></figure><p>It has been almost 44 years years since the first in vitro fertilisation (IVF) procedure was successfully performed in <a href="http://news.bbc.co.uk/1/hi/health/7505635.stm">1978 in Lancashire, England</a>. Since then, more than <a href="https://doi.org/10.1080/03009734.2020.1726534">8 million babies</a> have been born worldwide to assisted reproductive technologies, such as IVF.</p>
<p>But despite its increasing use, the success rate of IVF still remains relatively low, at around 30%. There may be a number of reasons for this. In our recent paper, we argue that this low rate is partially due to the many <a href="https://onlinelibrary.wiley.com/doi/10.1002/ctm2.864">unfavourable genetic changes</a> that we carry in our DNA.</p>
<p>Genetic changes happen when mutations in our genes replace, insert or delete sections of DNA. <a href="https://www.nature.com/articles/nrg2529">More of these mutations</a> are occurring now in humans because we’re having babies at a later age. As we get older, more <a href="https://www.sciencedaily.com/releases/2020/06/200619090528.htm#:%7E:text=As%20we%20get%20older%2C%20these,their%20children%20than%20younger%20parents.">mutations are likely to accumulate</a> – meaning older parents are more likely to pass on genetic mutations to their children than younger parents. Mutations may also be caused by <a href="https://doi.org/10.1534/genetics.115.180471">environmental factors</a> (such as ultraviolet radiation in sunlight), or lifestyle choices (for example, smoking). </p>
<p>All of the genetic changes we inherit or develop throughout our lifetime constitute what’s known as our genetic load. This genetic load can impact our ability to reproduce. And as <a href="https://onlinelibrary.wiley.com/doi/10.1002/ctm2.864">our study</a> suggests, this may also affect our ability to reproduce via methods such as IVF. </p>
<h2>Genetics and conception</h2>
<p>Genetic mutations make evolution possible. They provide the new material for natural selection that allows species to adapt and evolve. While most of these mutations have no effect, some are <a href="https://www.nature.com/articles/s41576-022-00448-x">slightly harmful</a>. Such harmful mutations may cause diabetes or <a href="https://www.dovepress.com/a-systematic-review-of-the-international-prevalence-of-brca-mutation-i-peer-reviewed-fulltext-article-CLEP">breast cancer</a>, for example – or they may disrupt the healthy development of an embryo.</p>
<p>Human DNA carries more than <a href="https://www.nature.com/articles/nature09534">1,000 harmful mutations</a>, most of which happened many generations ago. Yet, even though they are harmful, they have not (yet) been removed, because natural selection is a very slow process. </p>
<p>In addition to the large number of old mutations, new mutations also enter the population every generation. On average, every person acquires <a href="https://academic.oup.com/genetics/article/190/2/295/6064058">approximately 70 new mutations</a> during their lifetime. But since some of these mutations are harmful, they need to be removed by natural selection, so that they aren’t passed on to future offspring. One of the most important times this happens is during natural conception.</p>
<p>When a child is conceived naturally, the body has many mechanisms in place to remove some of these harmful mutations.</p>
<p>For example, the female reproductive system is designed in such a way that only the fittest sperm cells can reach the egg for fertilisation. Although evidence is scarce, animal studies suggest that the sperm that reach the fertilisation site have a better DNA quality and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2825232/">potentially fewer mutations</a>. </p>
<p>Mature eggs also undergo a sort of <a href="https://academic.oup.com/biolreprod/article/99/1/134/4862467">quality check</a> during fertilisation. This too helps purge some of the genetic load. The implantation stage (where a fertilised embryo implants itself in the mother’s womb) is also important, as many embryos with severe <a href="https://doi.org/10.3389/fgene.2021.667697">genetic abnormalities</a> tend to be lost naturally during pregnancies. </p>
<figure class="align-center ">
<img alt="A lab technician wearing blue surgical gloves uses a microscope to check IVF process." src="https://images.theconversation.com/files/465974/original/file-20220530-18-e6uwm5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/465974/original/file-20220530-18-e6uwm5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/465974/original/file-20220530-18-e6uwm5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/465974/original/file-20220530-18-e6uwm5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/465974/original/file-20220530-18-e6uwm5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/465974/original/file-20220530-18-e6uwm5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/465974/original/file-20220530-18-e6uwm5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">IVF largely bypasses natural selection.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/technician-blue-gloves-does-control-check-626843126">bezikus/ Shutterstock</a></span>
</figcaption>
</figure>
<p>However, IVF <a href="https://doi.org/10.1530/REP-17-0374">bypasses some of these natural mechanisms</a>. During IVF, multiple eggs are harvested from the woman’s ovaries and fertilised with sperm in a laboratory. After they have been fertilised, the embryos are then returned to the womb. This reduces the opportunity for natural selection, which may therefore make IVF less efficient in reducing the genetic load. This could potentially increase the likelihood that harmful variants of genes may be passed onto the next generation.</p>
<p>So, the genetic load has two big implications for human reproduction. First, the genetic load of parents affects their ability to successfully reproduce. This is true both for natural conception, as well as for IVF. Second, by relaxing natural selection, IVF may let more mutations slip through the net. As such, it could slowly increase our genetic load in future generation. But there may be a solution. </p>
<h2>The future of IVF</h2>
<p>Fertility rates have suffered an unprecedented decline in recent decades. In fact, sperm count has <a href="https://doi.org/10.1093/humupd/dmx022">fallen by about 50 to 60%</a> between 1973 and 2011. It’s unclear why this is, but if this trend continues it could mean more people turn to IVF to conceive. </p>
<p>Yet we still know surprisingly little about human reproduction and the selective processes operating during natural conception. We must understand natural conception first if we want to improve assisted reproduction methods, including IVF. But recent technological advances in assisted reproductive technologies mean that we may soon be better able to counteract some of the genetic load in humans. For example <a href="https://theconversation.com/older-sperm-produce-healthier-offspring-111711">selection at sperm level</a> in the IVF process has been shown to improve the offspring fitness in animal models. In particular, selection of longer-lived sperm in zebrafish results in healthier offspring that live longer. </p>
<p>Advances in genomic technologies also have the potential to affect human evolution. Already, genomic data is effectively being used in clinical care, and the genomic bases of <a href="https://www.nature.com/articles/s41586-020-2817-4">thousands of human diseases</a> are now known. Furthermore, changes to our environment and our lifestyle are affecting the genetic load and human health. Most often, <a href="https://doi.org/10.1534/genetics.115.180471">these changes have a negative effect</a>, which makes these technological advances ever more important. As new advances are made, it will also be important to consider the potential consequences of using assisted reproductive technologies if these become the norm.</p><img src="https://counter.theconversation.com/content/183295/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Cock Van Oosterhout receives funding from the Earth and Life Systems Alliance (ELSA), Norwich Research Park, UK.</span></em></p><p class="fine-print"><em><span>Daniel Marcu receives funding from the Biotechnology and Biological Sciences Research Council.</span></em></p><p class="fine-print"><em><span>Simone Immler receives funding from the Natrual Environment Research Council and the European Research Council. </span></em></p>Genetic mutations can impact our ability to reproduce – even via in vitro fertilisation.Cock Van Oosterhout, Professor of Evolutionary Genetics, University of East AngliaDaniel Marcu, PhD Researcher in Reproduction and Genetics, University of East AngliaSimone Immler, Professor of Genetics and Reproduction, University of East AngliaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1761382022-03-31T18:17:56Z2022-03-31T18:17:56ZThe Human Genome Project pieced together only 92% of the DNA – now scientists have finally filled in the remaining 8%<figure><img src="https://images.theconversation.com/files/455098/original/file-20220329-23-6gtdap.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2070%2C1449&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Over half of the human genome contains repetitive DNA sequences whose functions are still not fully understood.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/hands-dismantling-double-helix-royalty-free-illustration/1252382129">Malte Mueller/fStop via Getty Images</a></span></figcaption></figure><p>When the <a href="https://www.genome.gov/11006929/2003-release-international-consortium-completes-hgp">Human Genome Project</a> announced that they had completed the first human genome in 2003, it was a momentous accomplishment – for the first time, the DNA blueprint of human life was unlocked. But it came with a catch – they weren’t actually able to put together all the genetic information in the genome. There were gaps: unfilled, often repetitive regions that were too confusing to piece together.</p>
<p>With advancements in technology that could handle these repetitive sequences, scientists finally <a href="https://doi.org/10.1101/2021.05.26.445798">filled those gaps in May 2021</a>, and the first end-to-end human genome was <a href="https://www.science.org/doi/10.1126/science.abj6987">officially published on Mar. 31, 2022</a>.</p>
<p>I am a <a href="https://scholar.google.com/citations?user=q3BBiy8AAAAJ&hl=en">genome biologist</a> who studies repetitive DNA sequences and how they shape genomes throughout evolutionary history. I was part of the team that helped <a href="http://www.science.org/doi/10.1126/science.abk3112">characterize the repeat sequences</a> missing from the genome. And now, with a truly complete human genome, these uncovered repetitive regions are finally being explored in full for the first time.</p>
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<h2>The missing puzzle pieces</h2>
<p>German botanist Hans Winkler coined the word “<a href="https://doi.org/10.1371/journal.pgen.1006181">genome</a>” in 1920, combining the word “gene” with the suffix “-ome,” meaning “complete set,” to describe the full DNA sequence contained within each cell. Researchers still use this word a century later to refer to the genetic material that makes up an organism. </p>
<p>One way to describe what a genome looks like is to compare it to a reference book. In this analogy, a genome is an anthology containing the DNA instructions for life. It’s composed of a vast array of nucleotides (letters) that are packaged into chromosomes (chapters). Each chromosome contains genes (paragraphs) that are regions of DNA which code for the specific proteins that allow an organism to function.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/454831/original/file-20220328-15-5hb209.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram of chromosome unraveling to coiled DNA, genes and component nucleotides" src="https://images.theconversation.com/files/454831/original/file-20220328-15-5hb209.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/454831/original/file-20220328-15-5hb209.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=531&fit=crop&dpr=1 600w, https://images.theconversation.com/files/454831/original/file-20220328-15-5hb209.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=531&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/454831/original/file-20220328-15-5hb209.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=531&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/454831/original/file-20220328-15-5hb209.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=667&fit=crop&dpr=1 754w, https://images.theconversation.com/files/454831/original/file-20220328-15-5hb209.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=667&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/454831/original/file-20220328-15-5hb209.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=667&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Genetic material is made of DNA tightly packaged into chromosomes. Only select regions of the DNA in a genome contain genes coding for proteins.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/genes-vector-illustration-educational-royalty-free-illustration/1219077563">VectorMine/iStock via Getty Images Plus</a></span>
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<p>While every living organism has a genome, the size of that genome varies from species to species. An elephant uses the same form of genetic information as the grass it eats and the bacteria in its gut. But no two genomes look exactly alike. Some are short, like the genome of the insect-dwelling bacteria <a href="https://doi.org/10.1093/gbe/evt118"><em>Nasuia deltocephalinicola</em></a> with just 137 genes across 112,000 nucleotides. Some, like the 149 billion nucleotides of the flowering plant <a href="https://doi.org/10.1111/j.1095-8339.2010.01072.x"><em>Paris japonica</em></a>, are so long that it’s difficult to get a sense of how many genes are contained within.</p>
<p>But genes as they’ve traditionally been understood – as stretches of DNA that code for proteins – are just a small part of an organism’s genome. In fact, they make up <a href="https://dx.doi.org/10.1038%2Fnature11247">less than 2% of human DNA</a>. </p>
<p>The <a href="https://www.science.org/doi/10.1126/science.abj6987">human genome</a> contains roughly 3 billion nucleotides and just under 20,000 protein-coding genes – an estimated 1% of the genome’s total length. The remaining 99% is non-coding DNA sequences that don’t produce proteins. Some are regulatory components that work as a switchboard to control how other genes work. Others are <a href="https://doi.org/10.1155/2012/424526">pseudogenes</a>, or genomic relics that have lost their ability to function. </p>
<p>And <a href="https://doi.org/10.1101/2021.07.12.451456">over half</a> of the human genome is repetitive, with multiple copies of near-identical sequences. </p>
<h2>What is repetitive DNA?</h2>
<p>The simplest form of repetitive DNA are blocks of DNA repeated over and over in tandem called <a href="https://doi.org/10.3390/genes8090230">satellites</a>. While <a href="https://doi.org/10.1093/molbev/msq198">how much satellite DNA</a> a given genome has varies from person to person, they often cluster toward the ends of chromosomes in regions called <a href="https://doi.org/10.1016/j.febslet.2004.11.036">telomeres</a>. These regions protect chromosomes from degrading during DNA replication. They’re also found in the <a href="https://doi.org/10.3390/genes10030223">centromeres</a> of chromosomes, a region that helps keep genetic information intact when cells divide.</p>
<p>Researchers still lack a clear understanding of all the functions of satellite DNA. But because satellite DNA forms unique patterns in each person, forensic biologists and genealogists use this <a href="https://www.yourgenome.org/facts/what-is-a-dna-fingerprint">genomic “fingerprint”</a> to match crime scene samples and track ancestry. Over 50 genetic disorders are linked to variations in satellite DNA, including <a href="https://doi.org/10.1212/WNL.0b013e318249f683">Huntington’s disease</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/455099/original/file-20220329-15-1ohcqqe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="46 human chromosomes colored blue with white telomeres against a black screen" src="https://images.theconversation.com/files/455099/original/file-20220329-15-1ohcqqe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/455099/original/file-20220329-15-1ohcqqe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=638&fit=crop&dpr=1 600w, https://images.theconversation.com/files/455099/original/file-20220329-15-1ohcqqe.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=638&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/455099/original/file-20220329-15-1ohcqqe.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=638&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/455099/original/file-20220329-15-1ohcqqe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=802&fit=crop&dpr=1 754w, https://images.theconversation.com/files/455099/original/file-20220329-15-1ohcqqe.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=802&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/455099/original/file-20220329-15-1ohcqqe.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=802&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Satellite DNA tends to cluster toward the ends of chromosomes in their telomeres. Here, 46 human chromosomes are colored blue, with white telomeres.</span>
<span class="attribution"><a class="source" href="https://flic.kr/p/CRDw73">NIH Image Gallery/flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
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<p>Another abundant type of repetitive DNA are <a href="https://doi.org/10.1007/s10577-017-9569-5">transposable elements</a>, or sequences that can move around the genome.</p>
<p>Some scientists have described them as selfish DNA because they can insert themselves anywhere in the genome, regardless of the consequences. As the human genome evolved, many transposable sequences collected mutations <a href="https://doi.org/10.1186/s13100-016-0070-z">repressing</a> their ability to move to avoid harmful interruptions. But some can likely still move about. For example, transposable element insertions are linked to a number of <a href="https://doi.org/10.1186/s13100-016-0065-9">cases of hemophilia A</a>, a genetic bleeding disorder.</p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/IcbVDTLCDwI?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Transposable DNA may be the reason why humans have a tailbone but no tail.</span></figcaption>
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<p>But transposable elements aren’t just disruptive. They can have <a href="https://doi.org/10.1101/gr.218149.116">regulatory functions</a> that help control the expression of other DNA sequences. When they’re <a href="https://doi.org/10.1016/j.tig.2004.09.011">concentrated in centromeres</a>, they may also help maintain the integrity of the genes fundamental to cell survival.</p>
<p>They can also contribute to evolution. Researchers recently found that the insertion of a transposable element into a gene important to development might be why some primates, including humans, <a href="https://doi.org/10.1101/2021.09.14.460388">no longer have tails</a>. Chromosome rearrangements due to transposable elements are even linked to the genesis of new species like the <a href="https://doi.org/10.1093/molbev/msab148">gibbons of southeast Asia</a> and the <a href="https://doi.org/10.1146/annurev-animal-021419-083555">wallabies of Australia</a>.</p>
<h2>Completing the genomic puzzle</h2>
<p>Until recently, many of these complex regions could be compared to the far side of the moon: known to exist, but unseen.</p>
<p>When the <a href="https://www.genome.gov/11006929/2003-release-international-consortium-completes-hgp">Human Genome Project</a> first launched in 1990, technological limitations made it impossible to fully uncover repetitive regions in the genome. <a href="https://www.nature.com/scitable/topicpage/dna-sequencing-technologies-key-to-the-human-828/">Available sequencing technology</a> could only read about 500 nucleotides at a time, and these short fragments had to overlap one another in order to recreate the full sequence. Researchers used these overlapping segments to identify the next nucleotides in the sequence, incrementally extending the genome assembly one fragment at a time.</p>
<p>These repetitive gap regions were like putting together a 1,000-piece puzzle of an overcast sky: When every piece looks the same, how do you know where one cloud starts and another ends? With near-identical overlapping stretches in many spots, fully sequencing the genome by piecemeal became unfeasible. <a href="https://doi.org/10.1371/journal.pcbi.1003628">Millions of nucleotides</a> remained hidden in the the first iteration of the human genome.</p>
<p>Since then, sequence patches have gradually filled in gaps of the human genome bit by bit. And in 2021, the <a href="https://github.com/marbl/CHM13#telomere-to-telomere-consortium">Telomere-to-Telomere (T2T) Consortium</a>, an international consortium of scientists working to complete a human genome assembly from end to end, announced that all remaining gaps were <a href="https://www.science.org/doi/10.1126/science.abj6987">finally filled</a>. </p>
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<figcaption><span class="caption">With the completion of the first human genome, researchers are now looking toward capturing the full diversity of humanity.</span></figcaption>
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<p>This was made possible by improved sequencing technology capable of <a href="https://doi.org/10.1038/s41576-020-0236-x">reading longer sequences</a> thousands of nucleotides in length. With more information to situate repetitive sequences within a larger picture, it became easier to identify their proper place in the genome. Like simplifying a 1,000-piece puzzle to a 100-piece puzzle, long-read sequences made it <a href="http://www.science.org/doi/10.1126/science.abk3112">possible to assemble</a> large repetitive regions for the first time. </p>
<p>With the increasing power of long-read DNA sequencing technology, geneticists are positioned to explore a new era of genomics, untangling complex repetitive sequences across populations and species for the first time. And a complete, gap-free human genome provides an invaluable resource for researchers to investigate repetitive regions that shape genetic structure and variation, species evolution and human health.</p>
<p>But one complete genome doesn’t capture it all. Efforts continue to create diverse genomic references that fully represent <a href="https://humanpangenome.org">the human population</a> and <a href="https://www.earthbiogenome.org/">life on Earth</a>. With more complete, “telomere-to-telomere” genome references, scientists’ understanding of the repetitive dark matter of DNA will become more clear.</p>
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<p class="fine-print"><em><span>Gabrielle Hartley receives funding from the National Science Foundation. </span></em></p>Advances in technology have enabled researchers to sequence the large regions of repetitive DNA that eluded the Human Genome Project.Gabrielle Hartley, Ph.D. Candidate in Molecular and Cell Biology, University of ConnecticutLicensed as Creative Commons – attribution, no derivatives.