tag:theconversation.com,2011:/us/topics/gene-variants-11579/articlesGene variants – The Conversation2023-07-19T15:02:22Ztag:theconversation.com,2011:article/2097742023-07-19T15:02:22Z2023-07-19T15:02:22ZAsymptomatic COVID-19 is linked to a gene variant that boosts immune memory after exposure to prior seasonal cold viruses<figure><img src="https://images.theconversation.com/files/538083/original/file-20230718-33186-1uz5zq.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2429%2C1220&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Genetics may play a role in COVID-19 disease severity.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/virus-wide-royalty-free-image/1312985523">BlackJack3D/E+ via Getty Images</a></span></figcaption></figure><p><em>The <a href="https://theconversation.com/us/topics/research-brief-83231">Research Brief</a> is a short take about interesting academic work.</em></p>
<h2>The big idea</h2>
<p>A <a href="https://www.nature.com/articles/s41586-023-06331-x">common genetic variant</a> explains why some people are asymptomatic after being infected with the virus that causes COVID-19, according to our recently published study in the journal Nature.</p>
<p>Early in the pandemic, we were intrigued that many people did not develop COVID-19 symptoms while still testing positive for it. Because asymptomatic people are unlikely to seek medical help, we knew that collecting DNA samples to study the role of genetics in asymptomatic infections would be difficult. So instead, we took advantage of existing genetic data stored in the <a href="https://bethematch.org/about-us/how-we-help-patients/be-the-match-registry/">Be The Match</a> U.S. bone marrow donor registry. </p>
<p>We invited volunteers registered as donors to track their experience with COVID-19 via a smartphone app developed by the <a href="https://covid19.eurekaplatform.org">COVID-19 Citizen Science Study</a>. This allowed us to analyze the genetics of nearly 30,000 people without collecting biological samples and to identify COVID-19 positive individuals who never became sick.</p>
<p>We were particularly interested in analyzing the variation of <a href="https://www.uptodate.com/contents/human-leukocyte-antigens-hla-a-roadmap">human leukocyte antigen, or HLA, genes</a>. These key components of the immune system encode for proteins that display the viral particles that <a href="https://theconversation.com/coronavirus-b-cells-and-t-cells-explained-141888">T cells</a> – a group of immune system cells critical for fighting infections – recognize. Because HLA molecules are important in the immune response to pathogens and are highly variable among people, we thought they might play a role in COVID-19.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/538087/original/file-20230718-18870-crqach.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Computer illustration of HLA-B*1501." src="https://images.theconversation.com/files/538087/original/file-20230718-18870-crqach.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/538087/original/file-20230718-18870-crqach.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=815&fit=crop&dpr=1 600w, https://images.theconversation.com/files/538087/original/file-20230718-18870-crqach.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=815&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/538087/original/file-20230718-18870-crqach.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=815&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/538087/original/file-20230718-18870-crqach.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1024&fit=crop&dpr=1 754w, https://images.theconversation.com/files/538087/original/file-20230718-18870-crqach.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1024&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/538087/original/file-20230718-18870-crqach.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1024&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 is a 3D model of the protein that the gene variant HLA-B*15:01 codes for.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:HLA_B%5E1501.png">Pdeitiker/Wikimedia Commons</a></span>
</figcaption>
</figure>
<p>We found that 1,428 unvaccinated individuals reported a positive COVID-19 test, of whom 136 reported no COVID-19 symptoms. Our analysis identified a common variant of an HLA gene <a href="https://www.nature.com/articles/s41586-023-06331-x">called <em>HLA-B*15:01</em></a> that is associated with asymptomatic infection. This variant is present in <a href="https://doi.org/10.1016/j.humimm.2013.06.025">about 10% of the population with European ancestry</a>. </p>
<p>We found that people carrying the variant were more than twice as likely to remain asymptomatic after being infected with COVID-19, and those carrying two copies of this variant were more than eight times more likely to not have any symptoms. </p>
<p>Next, we used cells from people with the HLA variant who donated blood several years before the pandemic to see whether they had preexisting immunity to the virus that causes COVID-19. We found that people who had never been exposed to COVID-19 had memory T cells that worked against a specific particle of the virus, enabling them to elicit a very effective immune response against COVID-19. We also found that, when bound to HLA, this viral particle looks very similar to fragments of seasonal coronaviruses recognized by T cells. </p>
<p>Our findings suggest that <a href="https://www.nature.com/articles/s41586-023-06331-x">preexposure to seasonal cold viruses</a> allowed people with <em>HLA-B*15:01</em> to develop a very effective immune memory that helped them to quickly kill the virus before they developed symptoms. </p>
<h2>Why it matters</h2>
<p>Identifying the genetic factors associated with how the disease progresses after infection provides the basis for understanding why people respond differently to the virus that causes COVID-19 as well as other viral illnesses. Focusing on asymptomatic infections also sheds light on the early stages of infection and how the immune system fights against COVID-19. </p>
<p>Most existing vaccines protect against severe COVID-19 symptoms. Therefore, identifying the viral fragments that mediate asymptomatic infection, such as the one we discovered, can help develop more specific vaccines or therapies for COVID-19.</p>
<h2>What still isn’t known</h2>
<p>Although the genetic association we identified is strong, the immune system is very complex. It remains unclear what other mechanisms regulate asymptomatic infections, or why not everyone carrying this specific variant remains without symptoms.</p>
<h2>What’s next</h2>
<p>We want to know if the genetic variant we identified is shared by individuals from different ancestries. This will help us understand which genetic variants are important among those in these groups with asymptomatic COVID-19. We also hope to learn what makes the cross-reactive T cells in people with <em>HLA-B*15:01</em> so remarkably effective at keeping the symptoms associated with this virus at bay.</p><img src="https://counter.theconversation.com/content/209774/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jill Hollenbach receives funding from National Institutes of Health</span></em></p><p class="fine-print"><em><span>Danillo Augusto receives funding from the National Institutes of Health</span></em></p>Researchers found that people with a specific gene variant were two to eight times more likely to not have symptoms after infection.Jill Hollenbach, Professor of Neurology, University of California, San FranciscoDanillo Augusto, Assistant Professor of Biological Sciences, University of North Carolina – CharlotteLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1222202019-08-23T12:48:42Z2019-08-23T12:48:42ZAlzheimer’s: carriers of risk gene show brain changes in their 20s – here’s why we shouldn’t worry<figure><img src="https://images.theconversation.com/files/289065/original/file-20190822-170956-1sa2xi3.jpg?ixlib=rb-1.1.0&rect=215%2C89%2C5434%2C3485&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/hand-holding-paper-sheet-human-head-1221758086?src=RalI55W7sS9L68EwXctKvQ-1-5">StunningArt/Shutterstock</a></span></figcaption></figure><p>Dramatic developments in genetics research and the availability of commercial genetics tests have put us in a very modern predicament – we can now find out (quickly, easily and cheaply) whether we <a href="https://theconversation.com/sequencing-your-genome-is-becoming-an-affordable-reality-but-at-what-personal-cost-36720">personally hold genetic risk factors</a> that put us at a substantially increased risk of Alzheimer’s disease. In addition, we have <a href="https://www.sciencedirect.com/science/article/pii/S0197458018303348">recently shown</a> that brain changes can be identified in people holding these genetic risk variants as early as 20 years old.</p>
<p>Should we be testing ourselves? Should we worry? No. Here’s why:</p>
<p>Genetic research has revealed that some individuals carry variants of specific genes that confer an increased risk of developing <a href="https://youtu.be/wfLP8fFrOp0">Alzheimer’s disease</a> in later life. For example, carriers of the ε4 variant of the APOE gene are approximately <a href="https://www.ncbi.nlm.nih.gov/pubmed/8346443">three to eight times</a> more likely to be diagnosed with Alzheimer’s disease after age 60 than individuals without this variant. The more variants, the greater the risk – with a maximum of one inherited from each parent.</p>
<p>In our <a href="https://www.sciencedirect.com/science/article/pii/S0197458018303348">recent research</a>, we looked at these genetic factors in young people (around 20 years old, on average). We split them into “higher-risk” and “lower-risk” groups depending on whether they did or did not carry the APOE-ε4 gene variant, respectively.</p>
<p>Using <a href="https://www.sciencedirect.com/science/article/pii/S001094520800110X?via%3Dihub">advanced brain imaging techniques</a>, we were able to show that it is possible to detect subtle differences in particular brain networks for the “higher-risk” young adults, several decades before any clinical symptoms of Alzheimer’s emerge.</p>
<p>While <a href="https://www.sciencedirect.com/science/article/pii/S0197458018303348">brain structure</a> and <a href="https://www.nature.com/articles/srep16322">function</a> were significantly different between the risk groups on average, it is very important to point out that not all “higher-risk” individuals go on to develop Alzheimer’s disease. (Note that we say “higher” not “high” risk.)</p>
<p>The brains of many of these individuals were comparable to those at lower risk. This means carrying a higher-risk gene variant does not necessarily lead to early brain changes, or an Alzheimer’s diagnosis <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6148649/">later in life</a>.</p>
<h1>Should I get tested?</h1>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/289070/original/file-20190822-170951-k65352.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/289070/original/file-20190822-170951-k65352.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/289070/original/file-20190822-170951-k65352.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/289070/original/file-20190822-170951-k65352.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/289070/original/file-20190822-170951-k65352.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/289070/original/file-20190822-170951-k65352.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/289070/original/file-20190822-170951-k65352.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">Oral swaps and saliva samples are used by Direct To Consumer commercial genetic tests.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/young-woman-putting-ear-stick-into-446399410?src=9EmiICl3YxqNCikbeGBPhg-1-7">B-DSPiotrMarcinsk/Shutterstock</a></span>
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</figure>
<p>Public interest in genetics and gene testing is <a href="https://www.statista.com/chart/17023/commercial-genetic-testing/">booming</a>. Recent times have also seen highly publicised incidences of people responding to their own genetic risk with drastic interventions. For instance, Angelina Jolie, who <a href="https://theconversation.com/angelina-jolie-pitts-surgery-is-just-one-option-for-women-at-risk-of-cancer-39329">has a faulty copy of the BRCA1 gene</a>, associated with breast cancer – and <a href="https://scienceblog.cancerresearchuk.org/2013/05/14/angelina-jolie-inherited-breast-cancer-and-the-brca1-gene/">had elective surgery</a> to remove both breasts and some of her reproductive organs. </p>
<p>“Direct to consumer” genetic testing kits sold by companies now provide people with convenient and affordable access to their personal genetic information, including their genetic risk for specific diseases, including Alzheimer’s.</p>
<p>But the relatively low cost of these tests reflects the fact that they typically only cover a fraction of the genome. The results, therefore, neglect the contribution of the rest of the consumer’s genetic code. This will include other genes with protective, as well as negative, effects.</p>
<p>Of other concern, these tests have been shown to frequently generate false positive results: indeed, <a href="https://www.nature.com/articles/gim201838">one study found</a> approximately 40% of variants in a variety of genes reported in raw commercial genetic test data were false positives. This could lead to unnecessary distress, treatment and lifestyle adjustments. These tests also come with <a href="https://theconversation.com/were-not-prepared-for-the-genetic-revolution-thats-coming-96574">privacy and social concerns</a>.</p>
<p>On the upside, the popularity of commercial genetic testing partly reflects consumers’ positive desire to be proactive about their health. Consumers concerned about commercial genetic test findings should, however, request confirmatory tests from their clinician. These consumers should also understand that the disease risk reports they have purchased <a href="https://theconversation.com/genetic-home-testing-why-its-not-such-a-great-guide-to-your-ancestry-or-disease-risk-79604">at best provide a partial answer</a> to the question they are trying to address, because disease risk is about much more than genetics alone.</p>
<h1>I am at ‘higher’ risk of Alzheimer’s – what now?</h1>
<p>The next step for our research is to find out what leads some people at “higher-risk” to go on to develop these early brain changes, but not others. Do these people exercise or sleep less, maintain a poorer diet, or have poorer social relationships? Many possible answers involve lifestyle factors that could potentially be altered to “buffer” individuals against their genetic risk.</p>
<p>The only way to properly understand which lifestyle factors may have such a protective effect, is to study large numbers of people with varying degrees of genetic risk over several decades.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/289068/original/file-20190822-170935-14g1d9z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/289068/original/file-20190822-170935-14g1d9z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/289068/original/file-20190822-170935-14g1d9z.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/289068/original/file-20190822-170935-14g1d9z.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/289068/original/file-20190822-170935-14g1d9z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/289068/original/file-20190822-170935-14g1d9z.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/289068/original/file-20190822-170935-14g1d9z.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">Can lifestyle factors like reading, exercise and socialising protect us from our genetic risks as we age?</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/old-father-reading-newspaper-his-son-407783782?src=x4nybLT4uGKUNNhWfSncQA-1-4">RomanSamborskyi/Shutterstock</a></span>
</figcaption>
</figure>
<p>We are part of an international team of scientists undertaking one such study, led by Professors <a href="https://www.cardiff.ac.uk/people/view/151224-graham-kim">Kim Graham</a> and <a href="https://www.cardiff.ac.uk/people/view/357091-lawrence-andrew">Andrew Lawrence</a> at Cardiff University. The project involves collecting advanced brain imaging and cognitive test data from a large group of approximately 240 young adults. These individuals are part of a <a href="http://www.bristol.ac.uk/alspac/participants/">cohort</a> that has been studied since birth, so we can access a wealth of retrospective health and lifestyle data.</p>
<p>Smaller, isolated studies looking at lifestyle factors might currently be missing the big picture. Brain differences have been <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3583203/">found</a> in these high risk groups between people who do and don’t exercise regularly. This could suggest exercise has a <a href="https://content.iospress.com/articles/journal-of-alzheimers-disease/jad091531">protective effect</a> on the brain, and may in turn mitigate Alzheimer’s risk. It could also be that exercisers engage in other “protective” behaviours like <a href="https://www.tandfonline.com/doi/abs/10.1586/ern.11.56">eating a healthier diet</a>. It is only with large-scale cohort studies that we can begin to disentangle the genetic and lifestyle contributions to cognitive performance, the brain and Alzheimer’s risk.</p>
<p>Finally, if you are considering making lifestyle changes to offset your “genetic risk” for Alzheimer’s, taking regular exercise and maintaining a healthy lifestyle is seldom bad advice. Other drastic lifestyle changes, however, are likely unjustified.</p><img src="https://counter.theconversation.com/content/122220/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Dr Mark Postans is currently supported by funding from the Medical Research Council (grant MR/N01233X/1; awarded to Professor Kim Graham at Cardiff University)</span></em></p><p class="fine-print"><em><span>Carl J Hodgetts receives funding from Wellcome.</span></em></p>Scientists explain why commercial gene testing should be used with caution.Mark Postans, Postdoctoral research associate, Cardiff UniversityCarl Hodgetts, Research Fellow in Cognitive Neuroscience, Cardiff UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1169902019-05-27T01:58:23Z2019-05-27T01:58:23ZCurious Kids: are humans going to evolve again?<figure><img src="https://images.theconversation.com/files/273978/original/file-20190513-183109-hkq02k.jpg?ixlib=rb-1.1.0&rect=25%2C50%2C8447%2C2875&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Two-footed walking, large human brains and using stone tools are all examples of evolution.
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/1368998879?src=HXNReQ7wkSZkkNp6zSpQIg-3-11&size=huge_jpg">SpicyTruffel/Shutterstock</a></span></figcaption></figure><p><em><a href="https://theconversation.com/au/topics/curious-kids-36782">Curious Kids</a> is a series for children. If you have a question you’d like an expert to answer, send it to curiouskids@theconversation.edu.au You might also like the podcast <a href="http://www.abc.net.au/kidslisten/imagine-this/">Imagine This</a>, a co-production between ABC KIDS listen and The Conversation, based on Curious Kids.</em> </p>
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<blockquote>
<p><strong>Are humans going to evolve again? Thank you. – Temi Bisiriyu, age 10, London.</strong></p>
</blockquote>
<hr>
<p>Thanks for a great question, Temi. This is something I get asked a lot.</p>
<p>The short answer is that humans are evolving right now and will continue to do so even if we don’t notice it. This might sound a bit far-fetched, so let me explain what I mean.</p>
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<p>
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Read more:
<a href="https://theconversation.com/curious-kids-where-did-the-first-person-come-from-85891">Curious Kids: Where did the first person come from?</a>
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</em>
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<h2>The big changes</h2>
<p>Biologists who study evolution do so by examining evidence on two scales. The first scale is what we call macroevolution (“macro” means big). These are the big changes we see in the fossil record. They happen over long periods like hundreds of thousands, millions, or even tens of millions of years.</p>
<p>Think, for example, about the evolution of flowering plants or the appearance of mammals, both of which happened before 150 million years ago. </p>
<p>Or a bit closer to home, think of the evolution of our own biological group, the two-footed apes or hominins about 8 million years ago. Or of our species, <em>Homo sapiens</em>, which appeared in Africa more than 300,000 years ago.</p>
<p>I think this is the kind of evolution you have in mind. Most people think that evolution can only really be seen on this macro scale. Big changes like the evolution of two-footed walking or large human brains are examples of macroevolution.</p>
<h2>The small changes</h2>
<p>The other kind or evolution, which is not so obvious, happens on a very small scale. Scientists call it microevolution (“micro” means small). </p>
<p>These tiny changes have to do with genes and while they may not result in a new species forming, they can have big implications for the people involved.</p>
<p>One way this happens is completely at random, because of the way genes shuffle about when a new baby is made. Geneticists have found that with every new generation – say you and your friends – the makeup of your genes as a group will be a little bit different to your parents and their friends. </p>
<p>Geneticists call this “random genetic drift” and it can be very strong in small populations of people leading to rapid changes over short periods. </p>
<p>This process can explain why some problems like autoimmune disease, which were once rare, have become more common today. Multiple sclerosis and coeliac disease are examples of autoimmune diseases. </p>
<h2>How we live and what we eat</h2>
<p>Sometimes, the environment in which a group of people lives can led to changes in the gene pool of this community. And those changed genes can get passed on to the next generation.</p>
<p>A really powerful example is when people first began farming wheat, maize (corn) or rice many thousands of years ago. Because of that change, humans started to eat lot more starchy foods. </p>
<p>This led to some big physiological changes because some of these first farmers weren’t really able to digest large amounts of starch. </p>
<p>Over a short period of time — a couple of thousand years or even less — a gene that helped them digest starch (the amylase gene) became much more common in early farming communities.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/274227/original/file-20190514-60537-xem0c3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/274227/original/file-20190514-60537-xem0c3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/274227/original/file-20190514-60537-xem0c3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=404&fit=crop&dpr=1 600w, https://images.theconversation.com/files/274227/original/file-20190514-60537-xem0c3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=404&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/274227/original/file-20190514-60537-xem0c3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=404&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/274227/original/file-20190514-60537-xem0c3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=508&fit=crop&dpr=1 754w, https://images.theconversation.com/files/274227/original/file-20190514-60537-xem0c3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=508&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/274227/original/file-20190514-60537-xem0c3.jpg?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">When humans started farming maize (corn), that influenced the way we evolved.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/27518426@N03/5915757958/in/photolist-a1KNJS-LWH591-dwss3v-9pHuSW-hyoQf6-yjPVeE-d2uQMq-6c9EsC-fPfkgD-mxm86S-adBJZV-8zo2iG-9ACyp3-8gUTgM-T3dL7p-9KzT3h-XDZgHj-o9L6x6-fMJXE2-FL4dB-fN5jCm-fN2VyN-6tosFv-dGmaXi-6j67AC">Flickr/Pat Dalton...</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>In fact, people alive today whose ancestors were growing starchy foods have many more copies of this gene in their DNA than people whose ancestors didn’t. </p>
<p>Another example involves the gene that produces an enzyme called lactase, which allows adults to digest milk and other dairy products. If your ancestors drank a lot of milk, chances are you inherited that gene. Other people may have dairy intolerance because their ancestors didn’t drink as much milk. </p>
<p>So, as you you can see human evolution hasn’t really stopped. And understanding our evolution can tell us a lot about the health challenges we face today. </p>
<p>It might even help us to understand where we could be headed as humans shift the climate globally, perhaps even changing the future course of our evolution.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/curious-kids-how-do-bushfires-start-116664">Curious Kids: how do bushfires start?</a>
</strong>
</em>
</p>
<hr>
<p><em>Hello, curious kids! Have you got a question you’d like an expert to answer? Ask an adult to send your question to curiouskids@theconversation.edu.au</em></p>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/168011/original/file-20170505-21620-huq4lj.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/168011/original/file-20170505-21620-huq4lj.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=376&fit=crop&dpr=1 600w, https://images.theconversation.com/files/168011/original/file-20170505-21620-huq4lj.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=376&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/168011/original/file-20170505-21620-huq4lj.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=376&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/168011/original/file-20170505-21620-huq4lj.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=472&fit=crop&dpr=1 754w, https://images.theconversation.com/files/168011/original/file-20170505-21620-huq4lj.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=472&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/168011/original/file-20170505-21620-huq4lj.png?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">
<figcaption>
<span class="caption"></span>
<span class="attribution"><a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p><em>Please tell us your name, age and which city you live in. We won’t be able to answer every question but we will do our best.</em></p><img src="https://counter.theconversation.com/content/116990/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Darren Curnoe receives funding from the Australian Research Council. </span></em></p>Understanding our evolution can tell us a lot about the health challenges we face today.Darren Curnoe, Associate Professor and Chief Investigator, ARC Centre of Excellence for Australian Biodiversity and Heritage, University of New South Wales, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/999952018-10-26T10:42:26Z2018-10-26T10:42:26ZWhy do some people hurt more than others?<figure><img src="https://images.theconversation.com/files/242066/original/file-20181024-71011-1dwzhxe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Some people feel more pain than others.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/tattooist-makes-tattoo-287783510?src=C9ntmL1SaxczZYdTJCMDsw-1-6">Mikhail_Kayl / Shutterstock.com</a></span></figcaption></figure><p>Anyone who came of age in the 1990s remembers the “Friends” episode where Phoebe and Rachel venture out to get tattoos. Spoiler alert: Rachel gets a tattoo and Phoebe ends up with a black ink dot because she couldn’t take the pain. This sitcom storyline is funny, but it also simply illustrates the question that I and many others in the field <a href="http://doi.org/10.1038/nrrheum.2013.43">of</a> “<a href="http://doi.org/10.1136/jmedgenet-2011-100386">pain</a> <a href="http://doi.org/10.1016/j.pain.2013.09.018">genetics</a>” <a href="http://doi.org/10.1111/gbb.12302">are</a> <a href="http://doi.org/10.1172/JCI87406">trying</a> <a href="http://doi.org/10.2174/138920111798357393">to</a> <a href="http://doi.org/10.1038/nm.2710">answer</a>. What is it about Rachel that makes her different from Phoebe? And, more importantly, can we harness this difference to help the “Phoebes” of the world suffer less by making them more like the “Rachels”? </p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/242138/original/file-20181024-71020-1xw3won.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/242138/original/file-20181024-71020-1xw3won.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=614&fit=crop&dpr=1 600w, https://images.theconversation.com/files/242138/original/file-20181024-71020-1xw3won.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=614&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/242138/original/file-20181024-71020-1xw3won.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=614&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/242138/original/file-20181024-71020-1xw3won.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=771&fit=crop&dpr=1 754w, https://images.theconversation.com/files/242138/original/file-20181024-71020-1xw3won.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=771&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/242138/original/file-20181024-71020-1xw3won.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=771&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Are you a ‘Rachel’ or ‘Phoebe’ when it comes to pain?</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Associated-Press-Domestic-News-California-Unite-/0ea5d08fdde6da11af9f0014c2589dfb/2/0">AP Photo/Reed Saxon</a></span>
</figcaption>
</figure>
<p>Pain is the single most common symptom
reported when seeking medical attention. Under normal circumstances, pain signals injury, and the natural response is to protect ourselves until we have recovered and the pain subsides. Unfortunately, <a href="http://doi.org/10.1371/journal.pgen.1000086">people differ not only in their ability to detect, tolerate and respond to pain</a> but also in how they report it and how they respond to various treatments. This makes it difficult to know how to effectively treat each patient. So, why isn’t pain the same in everyone?</p>
<p>Individual differences in health outcomes often result from complex interactions of psychosocial, environmental and genetic factors. While pain may not register as a traditional disease like heart disease or diabetes, the same constellation of factors are at play. The painful experiences throughout our lifetime occur against a background of genes that make us more or less sensitive to pain. But our mental and physical state, previous experiences – painful, traumatic – and the environment can modulate our responses. </p>
<p>If we can better understand what makes individuals more or less sensitive to pain in all kinds of situations, then we are that much closer to reducing human suffering by developing targeted personalized pain treatments with lower risks of misuse, tolerance and abuse than the current treatments. Ultimately, this would mean knowing who is going to have more pain or need more pain-killing drugs, and then being able to effectively manage that pain so the patient is more comfortable and has a quicker recovery. </p>
<h2>Not all pain genes are the same</h2>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/242133/original/file-20181024-71017-ieu3zu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/242133/original/file-20181024-71017-ieu3zu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=440&fit=crop&dpr=1 600w, https://images.theconversation.com/files/242133/original/file-20181024-71017-ieu3zu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=440&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/242133/original/file-20181024-71017-ieu3zu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=440&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/242133/original/file-20181024-71017-ieu3zu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=553&fit=crop&dpr=1 754w, https://images.theconversation.com/files/242133/original/file-20181024-71017-ieu3zu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=553&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/242133/original/file-20181024-71017-ieu3zu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=553&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The level of pain an individual senses, mild to excruciating, depends on the types of pain associated genes.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/pain-level-conceptual-meter-indicate-maximum-225426601?src=H47dZxnkq-zpdgZ_0OiUbw-1-94">donskarpo / Shutterstock.com</a></span>
</figcaption>
</figure>
<p>With the sequencing of the human genome, we know a lot about the number and location of genes that make up our DNA code. Millions of small variations within those genes have also been identified, some that have known effects and some that don’t. </p>
<p>These variations can come in a number of forms, but the most common variation is the <a href="https://ghr.nlm.nih.gov/primer/genomicresearch/snp">single nucleotide polymorphism</a> – SNP, pronounced “snip” – representing a single difference in the individual units that make up DNA. </p>
<p>There are approximately 10 million known SNPs in the human genome; an individual’s combination of SNPs makes up his or her personal DNA code and differentiates it from that of others. When a SNP is common, it is referred to as a variant; when a SNP is rare, found in less than 1 percent of the population, then it is called a mutation. Rapidly expanding evidence implicates <a href="https://www.humanpaingenetics.org/hpgdb/">dozens of genes</a> and variants in determining our pain sensitivity, how well analgesics – like opioids – reduce our pain and even our risk for developing chronic pain.</p>
<h2>A history of pain tolerance</h2>
<p>The first studies of “pain genetics” were of families with an extremely rare condition characterized by the absence of pain. The first report of <a href="https://journals.lww.com/jonmd/Citation/1932/06000/A_Case_of_Congenital_General_Pure_Analgesia.2.asp">congenital insensitivity to pain</a> described “pure analgesia” in a performer working in a traveling show as “The Human Pincushion.” In the <a href="https://www.ncbi.nlm.nih.gov/pubmed/14209605">1960s</a> there were <a href="https://www.ncbi.nlm.nih.gov/pubmed/14177236">reports</a> of <a href="http://dx.doi.org/10.1136/jnnp.31.3.291">genetically</a> related families with children who were pain-tolerant.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/242099/original/file-20181024-71038-12vaw3w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/242099/original/file-20181024-71038-12vaw3w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=447&fit=crop&dpr=1 600w, https://images.theconversation.com/files/242099/original/file-20181024-71038-12vaw3w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=447&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/242099/original/file-20181024-71038-12vaw3w.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=447&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/242099/original/file-20181024-71038-12vaw3w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=562&fit=crop&dpr=1 754w, https://images.theconversation.com/files/242099/original/file-20181024-71038-12vaw3w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=562&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/242099/original/file-20181024-71038-12vaw3w.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=562&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Teacher’s aide Sue Price, right, examines Ashlyn Blocker’s head for scrapes, after she bumped it after school. Ashlyn never complains because the 5-year-old is among a small number of people in the world known to have congenital insensitivity to pain – a rare genetic disorder that makes her unable to feel pain.</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Associated-Press-Domestic-News-Georgia-United-S-/69578fe3eee0da11af9f0014c2589dfb/3/0">AP Photo/Stephen Morton</a></span>
</figcaption>
</figure>
<p>At that time the technology did not exist to determine the cause of this disorder, but from these rare families we know that CIP – now known by wonkier names like Channelopathy-associated insensitivity to pain and Hereditary Sensory and Autonomic Neuropathy – is the result of specific mutations or deletions within single genes required for transmitting pain signals. </p>
<p>The most common culprit is one of a small number of SNPs within SCN9A, a gene that encodes a protein channel necessary for sending pain signals. This condition is rare; only a handful of cases have been documented in the United States. While it might seem like a blessing to live without pain, these families must be always on alert for severe injuries or fatal illnesses. Typically children fall down and cry, but, in this case, there’s no pain to differentiate between a scraped knee and a broken knee cap. Pain insensitivity means that there is no chest pain signaling a heart attack and no lower right abdominal pain hinting at appendicitis, so these can kill before anyone knows that there is something wrong. </p>
<h2>Supersensitivity to pain</h2>
<p>Variations within SCN9A not only cause pain insensitivity, but have also been shown to trigger two severe conditions characterized by extreme pain: primary erythermalgia and paroxysmal extreme pain disorder. In these cases, the mutations within SCN9A cause more pain signals than normal. </p>
<p>These types of heritable pain conditions are extremely rare and, arguably, these studies of profound genetic variations reveal little about more subtle variations that may contribute to individual differences in the normal population. </p>
<p>However, with the growing public acceptance of genome-based medicine and calls for more precise personalized health care strategies, researchers are translating these findings into personalized pain treatment protocols that match a patient’s genes. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/242143/original/file-20181024-71026-kbljnb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/242143/original/file-20181024-71026-kbljnb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/242143/original/file-20181024-71026-kbljnb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/242143/original/file-20181024-71026-kbljnb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/242143/original/file-20181024-71026-kbljnb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/242143/original/file-20181024-71026-kbljnb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/242143/original/file-20181024-71026-kbljnb.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">Many of the answers to why pain sensitivity differs from person to person lies in our genes.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/sequencing-genome-background-on-subject-dna-792901510?src=-STUX5PnnQvYXMisZokyfA-2-19">Sergei Drozd / Shutterstock.com</a></span>
</figcaption>
</figure>
<h2>Do genetic variations affect pain in everyone?</h2>
<p>We know some of the major genes that influence pain perception and new genes are being identified all the time. </p>
<p>The SCN9A gene is a major player in controlling the body’s response to pain by activating or silencing the sodium channel. But whether it amplifies or dampens pain depends on the mutation an individual carries.</p>
<p>Estimates suggest that up to 60 percent of the variability in pain is the result of inherited – that is, genetic – factors. Stated simply, this means that pain sensitivity runs in families through normal genetic inheritance, much like height, hair color or skin tone. </p>
<p>Turns out that SCN9A also plays a role in pain in the normal population. A relatively more common SNP within SCN9A, called 3312G>T which occurs in 5 percent of the population, has been shown to determine sensitivity to <a href="http://doi.org/10.1097/ALN.0b013e31827dde74">post-operative pain</a> and how much opioid medication is needed to control it. <a href="https://doi.org/10.1073/pnas.0913181107">Another SNP</a> in SCN9A gene causes greater sensitivity for those with pain caused by osteoarthritis, lumbar disc removal surgery, amputee phantom limbs and pancreatitis. </p>
<h2>New painkillers from sea creatures</h2>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/242135/original/file-20181024-71020-1jhoxu4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/242135/original/file-20181024-71020-1jhoxu4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/242135/original/file-20181024-71020-1jhoxu4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=533&fit=crop&dpr=1 600w, https://images.theconversation.com/files/242135/original/file-20181024-71020-1jhoxu4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=533&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/242135/original/file-20181024-71020-1jhoxu4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=533&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/242135/original/file-20181024-71020-1jhoxu4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=670&fit=crop&dpr=1 754w, https://images.theconversation.com/files/242135/original/file-20181024-71020-1jhoxu4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=670&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/242135/original/file-20181024-71020-1jhoxu4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=670&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Pufferlike, like <em>Arothron meleagris</em> can produce a toxin that works by blocking the transmission of pain signals.</span>
<span class="attribution"><a class="source" href="https://upload.wikimedia.org/wikipedia/commons/1/11/Arothron_meleagris_by_NPS_1.jpg">NPS photo - Bill Eichenlaub</a></span>
</figcaption>
</figure>
<p>Therapeutically, we have been using local anesthetics, including lidocaine, to treat pain by inducing a short term block of the channel to stop pain transmission. These drugs have been continuously used to safely and effectively block pain for more than a century. </p>
<p>Interestingly, researchers are evaluating tetrodotoxin, a potent neurotoxin produced by sea creatures like pufferfish and octopuses, which works by blocking pain signal transmission, as a potential pain killer. They have shown early efficacy in <a href="https://www.ncbi.nlm.nih.gov/pubmed/21655148">treating cancer pain</a> and <a href="http://doi.org/10.3390/md10020281">migraine</a>. These drugs and toxins induce the same state that is present in those with congenital insensitivity to pain. </p>
<p>If there’s one silver lining to the opioid crisis, it is the realization that we need more precise tools to treat pain – ones that treat pain at the source and come with fewer side effects and risk. By understanding the genetic contribution to pain sensitivity, susceptibility to chronic pain and even analgesic response, we can then design treatments that address the “why” of pain and not just the “"where.” We’re beginning to design precision pain management strategies already, and the benefit to humankind will only increase as we know more about why pain differs among people.</p><img src="https://counter.theconversation.com/content/99995/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Erin Young receives funding from National Institutes of Health.
Erin Young is an Assistant Professor, University of Connecticut School of Nursing and Assistant Director of the Center for Advancement in Managing Pain (CAMP). </span></em></p>Researchers are exploring the genetic differences that dictate why some people suffer greater pain than others, and how to translate these findings into personalized pain treatments.Erin Young, Assistant Professor, University of Connecticut School of Nursing; Assistant Director, UCONN Center for Advancement in Managing Pain, University of ConnecticutLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/963982018-05-24T10:27:12Z2018-05-24T10:27:12ZWhat’s in your genome? Parents-to-be want to know<figure><img src="https://images.theconversation.com/files/219102/original/file-20180515-195330-1jqdzyc.jpg?ixlib=rb-1.1.0&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/good-looking-african-american-couple-cradles-485118664">By In The Light Photography/shutterstock.com</a></span></figcaption></figure><p>Every parent-to-be wants a healthy baby. And, when offered an opportunity, most couples want to know which disease-causing genes, or risk factors, they carry and could unwittingly pass to their children. </p>
<p>I’m a clinical molecular geneticist and wanted to understand exactly how much do people want to know about their genetic baggage. To address this question, I and a team of clinical geneticists, genetic counselors, laboratory geneticists and researchers screened approximately 200 healthy adults. We looked at 728 genes for disease-causing mutations and variants known to increase the risk of particular conditions. </p>
<p>What makes our tests different is that we are screening for a much larger number of genes and for all types of genetic defects not currently included in most of the clinically available carrier tests you would get from your OB-GYN. This information is critical for couples planning a family. But we discovered that collecting so much more genetic data raises a new set of complex issues that we have to address before such testing could be mainstreamed. </p>
<h2>How much information do you want?</h2>
<p>To prepare the participants for this potentially life-altering information, we provided genetic counseling before the genetic tests and again afterwards, as we gave them the results. Before an individual was tested, counselors asked what types of genetic conditions they wanted to receive. Did they only want to learn if they were carriers for serious life-threatening diseases or milder conditions as well? Did they want to know if they were carriers for diseases that hit in adulthood such as <a href="https://ghr.nlm.nih.gov/condition/hereditary-hemochromatosis">hereditary hemochromatosis</a>, an overload of iron in the tissues and organs, or spastic paraplegia, a nervous system disorder that affects walking? And what about unpredictable genetic conditions like <a href="https://ghr.nlm.nih.gov/condition/factor-v-leiden-thrombophilia">Factor V Leiden thrombophilia</a>, a blood clotting disorder, or <a href="https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-v">McArdle disease</a>, in which the body can’t break down glycogen in muscle cells? </p>
<p>To our surprise, most people, 93 percent, wanted all of their carrier information. Furthermore, 99 percent wanted to know about medically actionable conditions that put them at risk for conditions like breast or colon cancer or a heart muscle condition like cardiomyopathy. This underscores that most individuals feel that access to knowledge empowers them to make informed medical decisions.</p>
<h2>Why test individuals before conception?</h2>
<p>The individuals who participated <a href="https://doi.org/10.1016/j.ajhg.2018.04.004">in our study</a>, which was published in The American Journal of Human Genetics, were not affected by any known genetic condition. But our screening could reveal if a mother and father-to-be both carried a defect in the same gene. This is important information because if the child inherits one bad copy of the gene from each parent, then they suffer the disease. This is what happens in cystic fibrosis. </p>
<p>But with this new comprehensive genetic testing, couples who discovered that they both carried a genetic defect for the same inherited disorder can use this information to make informed reproductive decisions. They could opt for natural conception, prenatal diagnosis, pre-implantation genetic diagnosis, egg or sperm donation, or adoption. </p>
<p>As well as learning about people’s preferences for genetic testing results, we also discovered that most individuals carried between one and five disease-causing variants, which is a version of a gene known to raise the risk of a particular condition. This doesn’t mean that they will develop these diseases, but rather that they simply carry the gene defect and can pass it on to their children. </p>
<p>We also discovered that up to four out of every hundred participants carry a disease-causing variant that we call “medically actionable.” This means that a doctor can use the information to decrease the patient’s risk for disease with medications, or through lifestyle and environmental changes. </p>
<p>For example, we found some participants had a defect in the BRCA1 and BRCA2 genes that substantially increases a person’s risk to develop breast cancer and some other cancers. Knowing this information allows individuals to be closely monitored by medical screening procedures and eligible for potentially preventative treatment such as surgery. It also provides information for relatives who might want testing. </p>
<h2>Should detailed genetic testing be available for everyone?</h2>
<p>What made our study possible was new technology that enables us to sequence an individual’s entire genome – all 3 billion units of DNA – accurately and cheaply. The cost of sequencing alone for research purposes was approximately US$1,000, for each of the 200 participants. However, that did not cover the test interpretation or the genetic counseling costs. Geneticists have also become much better at interpreting the implications of carrying particular genetic variants. </p>
<p>Our test is not currently available to clinics that provide genetic screening services. But together with collaborators at the University of Washington and Kaiser Permanente NW, we studied whether we should offer this new technology to patients in the clinic. </p>
<p>One of the biggest challenges in clinical genome testing is how to determine whether a change in a gene is actually disease-causing or not. For our study we followed the <a href="https://doi.org/10.1038/gim.2015.30">recent guidelines</a> on how to interpret these gene changes from the American College of Medical Genetics and the Association of Molecular Pathology, which proved extremely useful in determining which genetic changes caused disease and which ones did not in this healthy reproductive population. But this information is not yet widely understood by everyday OB-GYN clinics.</p>
<p>Another hurdle is wrangling the enormous amount of data that is generated from the sequence of each individual’s DNA. We haven’t figured out how to read an individual’s entire genetic code and, in the absence of clinical symptoms, interpret the health implications of the thousands of genetic variations. </p>
<p>So we need more clinical knowledge and predictive tools. Returning results in a timely manner – four weeks or less – is challenging but critically important for individuals planning when and whether to have families. </p>
<p>Although we have the ability to sequence a patient’s genome, it isn’t clear that this is something we should do. We need to figure out whether it is useful and ethical to give patients so much information when we can’t say for sure what the health implications will be. </p>
<p>In the long run, we also need to figure out whether this type of testing improves the health of the patient. Finding answers to these questions will require more studies and collaboration with professional genetics societies and opinion leaders. So although this type of screening may be available in the future, there is still much work to be done.</p><img src="https://counter.theconversation.com/content/96398/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Carolyn Sue Richards receives funding from NIH.</span></em></p>We now have the capacity to quickly and cheaply sequence an individual’s genome and scour it for disease-causing genes. But how much, and what type, of information does a parent-to-be want to know?Carolyn Sue Richards, Professor of molecular and medical genetics, Oregon Health & Science UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/797392017-08-03T16:10:16Z2017-08-03T16:10:16ZGlobal genetic study involving different populations sheds light on glaucoma<figure><img src="https://images.theconversation.com/files/180858/original/file-20170803-5618-zy6vzq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Including different populations in genetic research studies can provide more varied results.</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p><a href="https://www.aao.org/eye-health/diseases/what-is-glaucoma">Glaucoma</a> is a group of diseases that damage the eye’s optic nerve and results in vision loss and irreversible blindness in some people. The diseases usually occur on their own but when they are caused by other conditions they are known as secondary glaucoma.</p>
<p>The most common cause of secondary glaucoma is exfoliation syndrome – a disease where abnormal protein is deposited throughout the body. When the protein deposits collect in the eye they may cause glaucoma. Exfoliation syndrome – which doesn’t always lead to secondary glaucoma – affects between <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2771265/">60 and 70 million people</a> </p>
<p>The syndrome is most common in <a href="https://www.ncbi.nlm.nih.gov/pubmed/17893012">Greek and Nordic people</a>. And at least 10% of the <a href="https://www.ncbi.nlm.nih.gov/pubmed/11371492?dopt=Abstract&holding=npg">population of Iceland</a> are affected. Although the syndrome is uncommon in <a href="https://www.ncbi.nlm.nih.gov/pubmed/25275896">African Americans</a> and virtually non-existent in <a href="https://www.ncbi.nlm.nih.gov/pubmed/23538512">West Africans</a>, it is the cause of glaucoma in up to 20% of <a href="https://www.ncbi.nlm.nih.gov/pubmed/11934321">black South Africans</a>. </p>
<p>Exfoliation syndrome has confounded scientists for decades. They have been unable to establish what causes the protein deposits to collect. This has made treating it hard. </p>
<p>The fact that the condition is common in some populations and uncommon in others suggests that it’s inherited and comes about as a result of a variation in the genes. If these were identified it could lead to unravelling the mechanisms underlying the disease – and ultimately lead to new treatments.</p>
<p><a href="http://www.jstor.org/stable/20037763">Early genetic studies</a> – performed on people of European descent – found that people who develop exfoliation syndrome that led to glaucoma had specific variants in the <em>LOXL1</em> gene. </p>
<p>We did a follow up <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861124/">study</a> in 2011 on South Africans which found similarities to the first studies as well as some differences, particularly in the way that the gene variants affected particular groups of people. These findings led to a <a href="http://www.nature.com/ng/journal/v49/n7/abs/ng.3875.html?foxtrotcallback=true">collaborative study</a> across six continents to clarify the gene variants in <em>LOXL1</em>. The aim was to identify genetic links that other population groups may have.</p>
<p>Our findings were remarkable. We identified five more genes associated with exfoliation syndrome, and established that some Japanese people have a different variant in <em>LOXL1</em> gene that in fact protects them from developing exfoliation syndrome.</p>
<p>What our study tells geneticists and ophthalmologists is that the <em>LOXL1</em> gene is important in patients with exfoliation syndrome, but there are also other genes and other factors involved in the condition. It has helped geneticists and ophthalmologists understand how complex the disease is and brought scientists closer to understanding an important contribution to blindness as a result of one form of glaucoma. </p>
<p>More importantly it highlights the importance of including different populations in research studies to provide more varied results. But we also know we still don’t have all the answers.</p>
<h2>An African variant</h2>
<p>In our <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861124/">2011 study</a> we set out to test the variation in the <em>LOXL1</em> gene by looking at African populations. The study involved people with and without exfoliation syndrome in Soweto, South Africa. We extracted DNA from blood samples and compared the <em>LOXL1</em> variants in the group of exfoliation patients from the variants in the group of control participants. </p>
<p>The study confirmed the findings of the earlier research on people of European descent: that the <em>LOXL1</em> variants were different in those who had the condition when compared with those who were unaffected.</p>
<p>But we discovered an important difference: surprisingly one of the variants associated with the disease in Europeans was associated with unaffected individuals in South Africa and vice versa. </p>
<p>Had this study not been done, geneticists would have been convinced that the first variant was the cause of the exfoliation syndrome. In fact, this isn’t the case – in South Africans its actually protective.. </p>
<p>These findings led to a global study to clarify the association with <em>LOXL1</em> and to identify other genetic associations among more varied groups across the world.</p>
<p>The large trans-ethnic study was led by a group from Singapore with collaborators worldwide. It involved close to 14 000 people who had exfoliation syndrome and over 110 000 people without. Participants came from 24 countries across six continents. </p>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861124/">Our study</a> identified five new genes linked to exfoliation syndrome. But it also found that some Japanese people had a rare genetic variant in the <em>LOXL1</em> gene – not seen in other populations – that protected them from developing exfoliation syndrome.</p>
<p>Detailed cellular experiments showed that this variant led to the formation of strong bonds between cells while the previously identified variants had no effect on these bonds. We believe that these strong bonds may make the cells more resistant to stress and therefore less likely to produce the exfoliation protein.</p>
<p>This finding may be the first step towards finding a way to stabilise cells. In turn, this could potentially lead the way towards a cure for the disease.</p>
<p>The African and Japanese patients changed the course of the research into exfoliation syndrome and its link to glaucoma. It led researchers to look for answers in different ways. The experiments that were performed suggested that some of the earlier hypotheses were wrong.</p>
<p>The findings have highlighted the value of doing genetic studies on different populations to understand the effect of genetic differences. They could potentially lead the way towards a cure for the disease.</p><img src="https://counter.theconversation.com/content/79739/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Susan Williams receives funding from NRF. </span></em></p><p class="fine-print"><em><span>Michèle Ramsay receives funding from the National Institutes of Health (USA) and the South African National Research Foundation and Department of Science and Technology. </span></em></p>There is value in including different populations in genetic research studies as has been shown in a study on exfoliation syndrome, which leads to glaucoma.Susan Williams, Lecturer in Ophthalmology, University of the WitwatersrandMichèle Ramsay, Director of the Sydney Brenner Institute for Molecular Bioscience, Professor in the Division of Human Genetics , University of the WitwatersrandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/695292017-01-29T16:41:16Z2017-01-29T16:41:16ZHow a gene test can solve side effects linked to ARV drugs in Africa<figure><img src="https://images.theconversation.com/files/154343/original/image-20170126-23845-2w3yp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">People with a certain gene have an adverse reaction to the antiretroviral efavirenz. </span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>Antiretrovirals have significantly improved the lives of people living with HIV. Today there are more than <a href="http://www.who.int/hiv/mediacentre/news/global-aids-update-2016-news/en/">17 million people on treatment</a> and the number of deaths from the disease has been <a href="http://www.who.int/bulletin/volumes/87/10/08-058982/en/">drastically reduced</a>. </p>
<p>But many people who take the treatment regimens daily experience <a href="http://i-base.info/ttfa/4-side-effects-of-arvs/">severe side effects</a>. Adverse drug reactions result in people not sticking to the treatment regime. This in turn leads to poor treatment outcomes and the risk of resistance developing.</p>
<p>One particular antiretroviral – efavirenz – presents a challenge. </p>
<p>It is considered one of the most <a href="http://link.springer.com/article/10.1007/s40274-016-3005-5/fulltext.html">cost effective antiretroviral treatments</a> available and is recommended by the World Health Organisation (WHO) as a <a href="http://www.who.int/hiv/pub/guidelines/arv2013/intro/rag/en/index4.html">firstline treatment</a> against HIV. By 2014 just less than half of all the people on antiretrovirals in low and middle income countries – that’s 8 million – were on the drug regime.</p>
<p>But up to 50% of patients taking it have to change treatment within a year. And the World Health Organisation has it on its list of drugs with the harshest side effects. People taking the drug can experience serious neuropsychiatric drug reactions including depression, nightmares, headaches and suicidal tendencies. </p>
<p>But there may be a solution. </p>
<p>Studies have shown that people who react particularly badly to efavirenz have a particular gene variant that messes with an enzyme responsible for processing the drug in their bodies. </p>
<p>We set out to find a way for patients to continue using the drug without the side effects. As part of <a href="http://www.clintonhealthaccess.org/content/uploads/2015/11/CHAI-ARV-Market-Report-2015_FINAL.pdf">our study</a> we developed a mechanism to test whether people have this gene. Those that test positive for the genetic variant can be put on reduced doses of the drug. It remains effective but is less toxic. </p>
<p>This is an important step because it addresses three problems: it makes it possible for people to stick to continuous treatment cycles; this in turn reduces the risk of resistance developing; and it means that a cost effective antiretroviral treatment can be administered better. </p>
<h2>Finding the problematic gene</h2>
<p>At the current dose of 600 mg daily patients who have variations of a specific gene – CYP2B6 – have a higher chance of developing side effects because of toxic blood levels. We did a continent wide population genotyping study with 11 major African populations groups to establish how prevalent this genetic variant was. </p>
<p>The population groups were the Yoruba, Ibo, Hausa tribes in Nigeria, the Kikuyu, Luo, Masaai in Kenya, mixed groups of Tanzania, the Venda in South Africa and the Shona, Ndebele and San in Zimbabwe.</p>
<p>We found there was a <a href="https://www.ncbi.nlm.nih.gov/pubmed/18057928">30% to 60% likelihood</a> of the genetic variant being found in African populations. This is compared to a 15% to 20% likelihood in white and Asian people.</p>
<p>Using this information we were able to derive a <a href="http://bmcpharmacoltoxicol.biomedcentral.com/articles/10.1186/s40360-015-0004-2">dosing algorithm</a> that could be used to tailor drug doses in patients with the gene variant.</p>
<p>The algorithm indicates that patients who have two low activity variants should be given 200 mg of the drug instead of the standard 600 mg. Those who have one normal activity and one low activity variant should be given 400 mg per day.</p>
<p><a href="http://www.clintonhealthaccess.org/content/uploads/2015/11/CHAI-ARV-Market-Report-2015_FINAL.pdf">Our studies</a> were done in our laboratory in Zimbabwe and then replicated in South Africa, Tanzania, Uganda and Ethiopia by independent research groups.</p>
<p>This algorithm is now being developed into a test kit – GeneDose-EFV test kit – which can be used in clinics. </p>
<h2>A quicker and cheaper solution</h2>
<p>It is not the first time that antiretrovirals have caused <a href="http://i-base.info/ttfa/4-side-effects-of-arvs/">serious side effects</a> in patients. But it took up to five years to physically <a href="http://journals.lww.com/aidsonline/Fulltext/2009/08240/Stavudine_in_antiretroviral_therapy__is_this_the.12.aspx">remove the drug</a> with side effects due to the number of places that it had been distributed to across the continent. </p>
<p>The widespread use of efavirenz on the continent, and the fact that it’s inexpensive, means there is an urgent need to address the burden of its adverse effects without dropping it as a treatment option. </p>
<p>There are several benefits from the test. Patients can stay on the drug by being given a dose they can tolerate. This, in turn, will result in increased treatment compliance among patients and therefore less of a risk for HIV drug resistance.</p>
<p>And for governments, it means they will still be able to administer cost effective antiretroviral treatment at a public health level and keep more patients on sustained antiretroviral treatment at a cheaper cost.</p><img src="https://counter.theconversation.com/content/69529/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Collen Masimirembwa works for the African Institute of Biomedical Science and Technology. He receives funding from SANBIO BIOFISAII. </span></em></p>Up to 50% of the people who take the efavirenz antiretroviral react particularly badly to it and need to change drug regimens.Collen Masimirembwa, Honorary Prof. of Clinical Pharmacology,, University of Cape TownLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/673262016-11-06T10:37:46Z2016-11-06T10:37:46ZUnderstanding Africa’s diverse gene pool can help fight lifestyle diseases<figure><img src="https://images.theconversation.com/files/144402/original/image-20161103-25339-1r777jp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">shutterstock</span> </figcaption></figure><p>Africa is home to about 16% of the world’s population. That’s 1.2 billion people. But the continent is disproportionately burdened by a double health challenge: infectious diseases and a <a href="https://theconversation.com/africa-needs-a-fresh-approach-to-lifestyle-diseases-research-66527">recent increase</a> in non-communicable diseases. </p>
<p>Non-communicable diseases such as hypertension, cardiovascular diseases and diabetes are on the march due to an ageing population, a transition to increased urbanisation, dietary changes, a more sedentary lifestyle and an increase in the prevalence of obesity.</p>
<p>Non-communicable diseases result in deaths everywhere in the world. But in Africa they are also a major reason for premature deaths, that is people dying between the ages of 40 and 70. In South Africa there is more than a 25% chance of dying prematurely from non-communicable diseases. On the rest of the continent it ranges between 15% and 24%. This compares to the average of less than 15% for the US and Europe.</p>
<p>The continent’s health systems are struggling to bring these diseases under control. One of the key strategies explored elsewhere is the use of genomics for a precision medicine approach. This opens the door to understanding which genetic drivers are responsible for an increased risk to a particular disease and how genetic variants in a population dictate responses to treatment. </p>
<p>Once scientists understand which treatments have the largest impact they can target therapy accordingly, this known as precision public health.</p>
<p>This approach could help to alleviate the health burden in Africa too but implementing it is more difficult than elsewhere. This is because the continent has added challenges. It has a genomic spectrum that is more diverse than other continents. In addition it has a wide range of different environments, cultures and levels of poverty. </p>
<p>That’s not to say it’s impossible. A precision public health approach would be possible if it was driven by research at a population level with large cohorts. This could help scientists understand how genes respond in the presence of certain environments, and interact with them (known as gene-environment interactions). Cracking this would open a new frontier in the drive against rising non-communicable diseases. </p>
<h2>Genomic research challenges</h2>
<p>There are four main problems with advancing genomic research in Africa. </p>
<p>Firstly, there is sparse data on genomics and gene-environment interactions in African populations. Scientists still do not know how populations with a particular genetic variant spectrum react to changes in the environment, such as an increase in poverty or lifestyle change during urbanisation, and what the likely impact of a particular genetic variants is. </p>
<p>In addition, scientists are prone to using interpretations based on research conducted elsewhere. There’s a particular bias, for example, to apply Eurocentric interpretations. In fact, people’s genetic background could have a profound effect on the way people react to their environment and to treatments. Applying a Eurocentric approach therefore doesn’t make sense. For example, sickle cell disease would not be very relevant in a European setting, but is very common in many regions of Africa and causes an enormous disease burden.</p>
<p>The second challenge is around the regulatory framework and how good practice guidelines are implemented. In many African countries privacy and genetic information is not protected or legislated. There is therefore the potential for harm.</p>
<p>Thirdly, there is a lack of resources to conduct primary research to inform precision public health approaches. These include money, people, infrastructure and electronic public health records. All are critical.</p>
<p>Implementing a precision public health approach is costly and it needs to be reviewed and updated continuously as understanding deepens and the environments that people live in change. </p>
<p>The fourth challenge is around informing people about the approach and what’s involved. Without this there is unlikely to be any buy in.</p>
<h2>First steps</h2>
<p>Genomic research has gained considerable momentum on the continent over the past decade. Two initiatives are boosting the capacity for genomic research on African populations. These are expected to benefit health initiatives elsewhere in the world too. </p>
<p>The International Network for the Demographic Evaluation of Populations and Their Health (INDEPTH) does two things: it collects data on populations. In addition it has launched a new initiative to collect biological specimens from populations. On the basis of this the project, known as <a href="http://www.thelancetnorway.com/pdfs/journals/langlo/PIIS2214-109X(15)00180-1.pdf">CHESS</a>, can provide data on diseases, pathogens and causes of death in specific populations.</p>
<p>The second initiative, the Human Heredity and Health in Africa <a href="http://www.h3africa.org">(H3Africa) Consortium</a>, studies infectious and non-communicable diseases from a genomics point of view. </p>
<p>These initiatives are important because they are studying populations that have been under-represented. </p>
<h2>Longterm goals</h2>
<p>There are several examples for successful use of precision medicine in the developed world (for example in some cancers). </p>
<p>Before Africa can boast its own examples it will first need to generate knowledge and data. This will take time which means that a precision public health approach to tackle disease won’t be yielding immediate results. </p>
<p>Many people on the continent do not get the treatment they need. In the short-term genomic research on drug responses could make a difference by providing governments with guidelines for what effective medication they should be giving their populations. </p>
<p>For longer term impact, researchers need to understand how genetic predisposition works in Africa. Only then will we begin to know how to treat the diseases more effectively.</p><img src="https://counter.theconversation.com/content/67326/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Michèle Ramsay receives funding from the SA Department of Science, the NRF and SAMRC and the National Institute of Health (USA).</span></em></p>Cracking genetic responses to the changing environment in Africa would open a new frontier in the drive against rising non-communicable diseases on the continent.Michèle Ramsay, Director of the Sydney Brenner Institute for Molecular Bioscience, Professor in the Division of Human Genetics , University of the WitwatersrandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/575382016-05-05T10:09:08Z2016-05-05T10:09:08ZSimulating evolution: how close do computer models come to reality?<figure><img src="https://images.theconversation.com/files/121082/original/image-20160503-13603-1w9luwb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Computers can be our prediction machines.</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic.mhtml?id=284581217&src=lb-29877982">Data image via www.shutterstock.com.</a></span></figcaption></figure><p>Darwin’s <a href="https://en.wikipedia.org/wiki/Evolution">theory of evolution</a> is a simple but powerful framework that explains how complexity can come from simplicity: how everything biological around us – from the microbial biofilms on your teeth to the majestic redwood trees – emerged from the very simplest of beginnings.</p>
<p>How exactly this happened is, of course, a matter of intense research. Each species is finely adapted to thrive in its environment, which in turn has shaped that species’ evolutionary history. But those environmental forces exerted on a species occurred over a very long period of time, in the often very distant past. How can we understand which environmental features were responsible for which adaptations we see today?</p>
<p>As an example, my research group recently got interested in what makes people dislike taking risks. Of course we can’t travel through time to go back and run a controlled experiment on our early human ancestors to see how that tendency might have evolved. But as scientists, we want to do more than just come up with an untestable hypothesis.</p>
<p>So we turned to computers to simulate the dynamics of ancient people for thousands of generations. By carefully choosing the starting parameters for our computer simulation, we were able to see how in small groups of about 150 people – the size common during the Stone Age – gambles that pay off big time (but only rarely) end up being genetically costly. <a href="http://www.nature.com/articles/srep08242">We also found</a> that risky behavior had no consequences as long as populations were large. I can’t think of another way an evolutionary study like this could have been carried out. Here’s why we can believe what these kinds of computer simulations tell us.</p>
<h2>Passing on a constant flux of traits</h2>
<p>Darwin’s theory of evolution is simple in the sense that it requires only three necessary (and sufficient) components for the process to work: inheritance, variations and differential survival (sometimes called “selection”).</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/121053/original/image-20160503-19871-182nnx2.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/121053/original/image-20160503-19871-182nnx2.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/121053/original/image-20160503-19871-182nnx2.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=544&fit=crop&dpr=1 600w, https://images.theconversation.com/files/121053/original/image-20160503-19871-182nnx2.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=544&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/121053/original/image-20160503-19871-182nnx2.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=544&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/121053/original/image-20160503-19871-182nnx2.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=683&fit=crop&dpr=1 754w, https://images.theconversation.com/files/121053/original/image-20160503-19871-182nnx2.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=683&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/121053/original/image-20160503-19871-182nnx2.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=683&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Natural selection is one mechanism for how evolution happens.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Mutation_and_selection_diagram.svg">Elembis</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
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<p>Inheritance guarantees that anything new discovered by the process is not lost. Variation ensures that new things are being tried out constantly. And differential survival implies that differences matter – variations that help rather than hurt have consequences for the descendants of the first individual that carried that beneficial change.</p>
<p>But even though these principles are straightforward, how they play out in a complex world is far from simple. We might be able to work out in our head how one beneficial change (say, a larger body size that allows an individual to withstand a predator’s assaults) can also have negative consequences (more time spent foraging to support the body weight exposes the individual to more predation). Such simple trade-offs can be captured by mathematical formulas, and their consequences can be worked out. </p>
<p>But in real biology, every single trait could conceivably affect every other. It’s not easy to work out the net benefit of a set of traits, either in your head or with mathematics. This is where computers come in. </p>
<h2>Computers run through scenarios, fast</h2>
<p>What computers really do within scientific research is often misrepresented or misunderstood. I frequently hear the phrase: “With a computer, you can get any result you want.” But this is not true. What a computer does is keep track of things for you.</p>
<p>To a large extent, this is what mathematics does too. I like to point out that mathematics is “the crutch of the feeble-minded”; it allows us to use symbols to embody complex relationships that we can then manipulate according to strict rules.</p>
<p>The computer is no different, except it allows us to keep track of vastly more variables, and to work out the consequences of the relationships over long periods of time. Since we set strict rules, of course, we can’t get “anything we want.” We get only what is allowed according to the rules.</p>
<p>But what are those rules?</p>
<p>In mathematics, you start with a set of assumptions, and you work out the consequences according to the rules of logic. This is still true inside a computer, but now we can also implement very specific rules – for example, the laws of chemistry, the effects of friction or the cost of finding a mate. </p>
<p>Researchers in a variety of fields turn to computer simulations to help them test ideas that they can’t investigate any other way. Astrophysicists use these kinds of models to <a href="http://doi.org/10.1111/j.1365-2966.2008.14106.x">simulate how stars form</a>. Material scientists simulate the <a href="https://en.wikipedia.org/wiki/Stockpile_stewardship">aging of nuclear weapons</a> to predict if they will still work in the future. </p>
<p>In evolutionary biology, we might ask which factor shaped a particular trait or behavior. For instance, my colleague <a href="http://hyenas.zoology.msu.edu/">Kay Holekamp</a> has been observing hyenas in Kenya for over 25 years, and she’s collected an enormous data set pertaining to the hunting habits (among other traits) of these animals. But even all those observations can’t tell us <em>why</em> she sees what she sees in the field. The reasons may lie in pressures that the population was under in the past, or maybe the pressures manifest themselves only over thousands of generations.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/121055/original/image-20160503-27777-l56foy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/121055/original/image-20160503-27777-l56foy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/121055/original/image-20160503-27777-l56foy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=195&fit=crop&dpr=1 600w, https://images.theconversation.com/files/121055/original/image-20160503-27777-l56foy.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=195&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/121055/original/image-20160503-27777-l56foy.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=195&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/121055/original/image-20160503-27777-l56foy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=244&fit=crop&dpr=1 754w, https://images.theconversation.com/files/121055/original/image-20160503-27777-l56foy.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=244&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/121055/original/image-20160503-27777-l56foy.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=244&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">Even decades of observation leave us with questions about why animals behave in certain ways.</span>
<span class="attribution"><a class="source" href="http://hyenas.zoology.msu.edu/index.php?mact=Album,m4,default,1&m4albumid=1&m4returnid=52&page=52">Anne Engh</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
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<p>To answer questions such as “Why don’t the highest-ranking female hyenas participate in the hunt?,” we have to study the consequences of different assumptions on the long-term survival of the group. </p>
<p>Evolutionary theory says that only beneficial traits survive in the long run, but it can often be hard to understand how a certain trait might help. This is because of all those trade-offs I mentioned, and sometimes the benefit of a trait only becomes clear after a long time. After all, evolution has had millions of years of trials, failures and successes. Even 50 years of observation might not reveal to us the long-term consequences of a set of traits and how they interact and play out in a complex world.</p>
<p>But a computer might work this out in minutes, as a population of 1,000 gazelles and a group of, say, 150 hyenas can be followed over thousands of simulated generations. </p>
<h2>Matching theory to observation</h2>
<p>In evolutionary science, computers thus are prediction machines: they answer questions like “What would happen under these rules, given I started in <em>this</em> world with <em>these</em> starting conditions?” </p>
<p>In our study of the evolutionary origins of risk aversion, for example, we could ask what happens to risk aversion if the total population was large, but composed of small groups with migration between them. Running the scenario, we found that risk aversion still evolved unless the migration rate was exceedingly high. </p>
<p>Of course, if you start with the wrong rules, or inappropriate starting conditions, the results may not match what we observe in reality. But this is exactly what we require in the scientific process. If the predictions are wrong, then we must modify either the rules, or the initial conditions (or both).</p>
<p>Once we do obtain a match between the computer simulations and real-world observations, we can’t stop there and conclude we’ve discovered the rules that correctly reflect what is happening in nature. We must, instead, test whether these rules <em>also</em> predict other things that we didn’t set out to test in the first place. For example, do the same set of rules also explain the observation that the spoils of a kill are not distributed equally among the hyenas? </p>
<p>This kind of thinking is no different from the way theory and experiment have worked in unison to build the complex and powerful framework of theoretical physics. In that quest, theories were laid down, for the most part, mathematically. In evolutionary biology, though, this is usually not possible simply because biology is too complicated.</p>
<p>Evolutionary simulations allow us to test hypotheses, but they’re not asking or even answering questions. <em>We</em> ask “What if,” and the computer dutifully responds: “In this case, this is what you would get.” The computer helps us “think forward in time” with blazing speed, and in evolutionary science this is precisely what is required to generate understanding.</p><img src="https://counter.theconversation.com/content/57538/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Christoph Adami receives funding from the National Science Foundation. </span></em></p>Scientists of all kinds turn to computer models to investigate questions they can’t get at any other way. Here’s how models work and why we can trust them.Christoph Adami, Professor of Microbiology and Molecular Genetics & Physics and Astronomy, Michigan State UniversityLicensed as Creative Commons – attribution, no derivatives.