tag:theconversation.com,2011:/uk/topics/genome-837/articlesGenome – The Conversation2024-02-22T18:16:18Ztag:theconversation.com,2011:article/2190722024-02-22T18:16:18Z2024-02-22T18:16:18ZExtreme environments are coded into the genomes of the organisms that live there<p>An organism’s genome is a set of DNA instructions needed for its development, function and reproduction. The genome of a present-day organism contains information from its journey on an evolutionary path that starts with the
“<a href="https://doi.org/10.1007/978-3-030-30363-1_3">first universal common ancestor</a>” of all life on Earth and culminates with that organism. </p>
<p>Encoded within itself, an organism’s genome contains information that can reveal connections to its ancestors and its relatives.</p>
<h2>Other dimensions of the genome</h2>
<p>Our research explores the hypothesis that an organism’s genome could contain other types of information, <a href="https://doi.org/10.1038/s41598-023-42518-y">beyond genealogy or taxonomy</a>. We asked: Could the genome of an organism contain information that would allow us to determine the type of environment the organism lives in?</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/574213/original/file-20240207-16-upk4fk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="a large black lake" src="https://images.theconversation.com/files/574213/original/file-20240207-16-upk4fk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/574213/original/file-20240207-16-upk4fk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/574213/original/file-20240207-16-upk4fk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/574213/original/file-20240207-16-upk4fk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/574213/original/file-20240207-16-upk4fk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/574213/original/file-20240207-16-upk4fk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/574213/original/file-20240207-16-upk4fk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=502&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Extremophiles have been found in environments such as Pitch Lake in Trinidad and Tobago, the largest asphalt deposit in the world.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>As unlikely as it seems, our team of computer science and biology researchers at the University of Waterloo and Western University found that to be the case for extremophiles — organisms that live and thrive in extremely harsh conditions. These environmental conditions range from extreme heat (over 100 C) to extreme cold (below -12 C), high radiation or extremes in acidity or pressure.</p>
<h2>DNA as a language</h2>
<p>We looked at genomic DNA as a text written in a “DNA language.” A DNA strand (or DNA sequence) consists of a succession of <a href="https://www.genome.gov/genetics-glossary/Nucleotide">basic units called nucleotides</a>, strung together by a sugar-phosphate backbone. There are four such different DNA units: <a href="https://www.genome.gov/genetics-glossary/acgt">adenine, cytosine, guanine and thymine (A,C,G,T)</a>. </p>
<p>Viewed abstractly, a DNA sequence can be thought of as a line of text, written with “letters” from the “DNA alphabet.” For example, “CAT” would be the three-letter “DNA word” corresponding to the three-unit DNA sequence cytosine-adenine-thymine.</p>
<p>In the 1990s, it was discovered that by <a href="https://doi.org/10.1093/nar/18.8.2163">counting occurrences</a> of such DNA words in a short DNA sequence extracted from the genome of an organism, one could identify <a href="https://doi.org/10.1093/oxfordjournals.molbev.a026048">the species of the organism</a> and the degree of its relatedness to other organisms in the evolutionary “<a href="https://doi.org/10.1038/nmicrobiol.2016.48">tree of life</a>.”</p>
<p>The mechanism of this identification or classification of an organism based on DNA word counts is similar to the process that allows us to differentiate an English book from a French book: By taking one page from each book one notices that the English text has many occurrences of the three-letter word “the,” while the French text has many occurrences of the three-letter word “les.”</p>
<p>Note that the word-frequency profile of each book is not dependent on the particular page we chose to read and on whether we considered multiple pages, a single page or an entire chapter. Similarly, the frequency profile of DNA words in a genome is not dependent on the location and on the length of the DNA sequence that was selected to represent that genome.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/574232/original/file-20240207-33-kdilvj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="rows of lights with the letters C, A, G, T projected from them" src="https://images.theconversation.com/files/574232/original/file-20240207-33-kdilvj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/574232/original/file-20240207-33-kdilvj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=420&fit=crop&dpr=1 600w, https://images.theconversation.com/files/574232/original/file-20240207-33-kdilvj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=420&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/574232/original/file-20240207-33-kdilvj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=420&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/574232/original/file-20240207-33-kdilvj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=528&fit=crop&dpr=1 754w, https://images.theconversation.com/files/574232/original/file-20240207-33-kdilvj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=528&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/574232/original/file-20240207-33-kdilvj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=528&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A DNA strand consists of a succession of basic units: adenine, cytosine, guanine and thymine (ACGT).</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>That DNA word-frequency profiles can act as a “genomic signature” of an organism was a significant discovery and, until now, it was believed that the DNA word-frequency profile of a genome only contained evolutionary information pertaining to the species, genus, family, order, class, phylum, kingdom or domain that the organism belonged to.</p>
<p>Our team set out to ask whether the DNA word-frequency profile of a genome could reveal other kinds of information — for example, information regarding the type of extreme environment that a microbial extremophile thrives in.</p>
<h2>Environment imprints in extremophile DNA</h2>
<p>We used a dataset of 700 microbial extremophiles living in extreme temperatures (either extreme heat or cold) or extreme pH conditions (strongly acidic or alkaline). We used both <a href="https://doi.org/10.1093/bioinformatics/btz918">supervised machine learning</a> and <a href="https://doi.org/10.1093/bioinformatics/btad508">unsupervised machine learning</a> computational approaches to test our hypothesis.</p>
<p>In both types of environmental conditions, we discovered that we could clearly detect an environmental signal indicating the type of extreme environment a particular organism inhabited. </p>
<p>In the case of unsupervised machine learning, a “blind” algorithm was given a dataset of extremophile DNA sequences (and no other information about either their taxonomy or their living environment). The algorithm was then asked to group these DNA sequences in clusters, based on whatever similarities it could find among their DNA word-frequency profiles. </p>
<p>The expectation was that all the clusters discovered this way would be along taxonomic lines: bacteria grouped with bacteria, and archaea grouped with archaea. To our great surprise, this was not always the case, and some archaea and bacteria were consistently grouped together, no matter what algorithms we used. </p>
<p>The only obvious commonality that could explain their being considered similar by the multiple machine learning algorithms was that they were heat-loving extremophiles.</p>
<h2>A shocking discovery</h2>
<p>The <a href="https://doi.org/10.1038/s41467-023-42924-w">tree of life</a>, a conceptual framework used in biology that <a href="https://doi.org/10.1073/pnas.87.12.4576">represents geneaological relationships</a> between species, has three major limbs, called domains: <a href="https://doi.org/10.1073/pnas.74.11.5088">bacteria, archaea and eukarya</a>.</p>
<p>Eukaryotes are organisms that have a membrane-bound nucleus, and this domain includes animals, plants, fungi and the unicellular microscopic protists. In contrast, bacteria and archaea are single-cell organisms that do not have a membrane-bound nucleus containing the genome. What distinguishes bacteria from archaea is the composition of their cell walls.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/576771/original/file-20240220-22-6gkrf4.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="a figure showing the three branches of the tree of life" src="https://images.theconversation.com/files/576771/original/file-20240220-22-6gkrf4.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/576771/original/file-20240220-22-6gkrf4.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=485&fit=crop&dpr=1 600w, https://images.theconversation.com/files/576771/original/file-20240220-22-6gkrf4.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=485&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/576771/original/file-20240220-22-6gkrf4.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=485&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/576771/original/file-20240220-22-6gkrf4.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=610&fit=crop&dpr=1 754w, https://images.theconversation.com/files/576771/original/file-20240220-22-6gkrf4.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=610&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/576771/original/file-20240220-22-6gkrf4.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=610&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A schematic tree of life with the primary domains, archaea and bacteria, shown in purple and blue, respectively and the secondary domain, Eukaryotes, in green.</span>
<span class="attribution"><a class="source" href="https://www.eurekalert.org/multimedia/1006461">(Tara Mahendrarajah)</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>The three domains of life are dramatically different from each other and, genetically, a bacterium is as different from an archaeon as a polar bear (eukarya) is from an <em>E. coli</em> (bacteria). </p>
<p>The expectation was therefore that the genome of a bacterium and of an archaeon would be as far apart as possible in any clustering by any genomic similarity measure. Our finding of some bacteria and archaea clustered together, apparently just because they are both adapted to extreme heat, means that the extreme temperature environment they live in caused pervasive, genome-wide, systemic shifts in their genome language. </p>
<p>This discovery is akin to finding a completely new dimension of the genome, an environmental one, existent in addition to its well-known taxonomic dimension.</p>
<h2>Genomic impact of other environments</h2>
<p>Besides being unexpected, this finding could have implications for our understanding of the evolution of life on Earth, as well as guide our thinking into what it would take to live in outer space. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/576775/original/file-20240220-16-7aq8tz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="an orange sphere with a tail" src="https://images.theconversation.com/files/576775/original/file-20240220-16-7aq8tz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/576775/original/file-20240220-16-7aq8tz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=449&fit=crop&dpr=1 600w, https://images.theconversation.com/files/576775/original/file-20240220-16-7aq8tz.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=449&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/576775/original/file-20240220-16-7aq8tz.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=449&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/576775/original/file-20240220-16-7aq8tz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=565&fit=crop&dpr=1 754w, https://images.theconversation.com/files/576775/original/file-20240220-16-7aq8tz.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=565&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/576775/original/file-20240220-16-7aq8tz.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=565&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>Pyrococcus furiosus</em>, a thermophilic archaeon that was surprisingly grouped with thermophilic bacteria.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:P_furiosus.jpg">(Michelle Kropf/Wikimedia Commons)</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Indeed, our ongoing research is exploring the existence of an environmental signal in the genomic signature of radiation-resistant extremophiles, such as <a href="https://doi.org/10.1089/ast.2020.2424"><em>Deinococcus radiodurans</em></a>, which can survive radiation exposure, as well as <a href="https://doi.org/10.1101/cshperspect.a012765">cold</a>, <a href="https://doi.org/10.1128/jb.178.3.633-637.1996">dehydration</a>, <a href="https://doi.org/10.3389/fmicb.2019.00909">vacuum conditions</a> and acid, and was shown to be able to survive in <a href="https://doi.org/10.1089/ast.2020.2424">outer space for up to three years</a>.</p><img src="https://counter.theconversation.com/content/219072/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Kathleen A. Hill receives funding from the Natural Sciences and Engineering Research Council of Canada (NSERC).</span></em></p><p class="fine-print"><em><span>Lila Kari receives funding from the Natural Sciences and Engineering Research Council of Canada (NSERC). </span></em></p>Computer analysis of the genomes of extremophiles — organisms that live in extreme environments — reveals that their living conditions are recorded in their DNA.Kathleen A. Hill, Associate Professor Biology, Western UniversityLila Kari, Professor, Computer Science, University of WaterlooLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2196832024-02-05T23:06:31Z2024-02-05T23:06:31ZGenetic diseases: How scientists are working to make DNA repair (almost) a piece of cake<figure><img src="https://images.theconversation.com/files/564984/original/file-20231101-27-722eas.jpg?ixlib=rb-1.1.0&rect=5%2C0%2C992%2C561&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">An error in DNA is called a mutation.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>I have always been fascinated by genetics, a branch of biology that helps explain everything from the striking resemblance between different members of a family to the fact that strawberry plants are frost-resistant. It’s an impressive field!</p>
<p>I also have a personal connection to genetics. Growing up, I learned that members of my family had a form of <a href="https://doi.org/10.3390/jcm12186011">muscular dystrophy</a> called dysferlinopathy. I watched as my mother gradually lost the ability to climb stairs and had to use a cane, then a walker, and finally a wheelchair to get around. Her leg muscles were less and less able to repair themselves and became weaker with time.</p>
<p>My parents explained to me that all these changes were due to the error of a single letter among the billions of letters in a long DNA sequence. This error prevents the production of the protein <a href="https://doi.org/10.3390/jcm12144769">responsible for repairing arm and leg muscles</a>.</p>
<p>Today, I am a doctoral research student in molecular medicine. I study the treatment of hereditary diseases in order to be able to help families like my own. In this article, I will demystify hereditary diseases and show what research is being carried out to treat them.</p>
<h2>A piece of cake? Not quite</h2>
<p>Let’s start by imagining DNA as a recipe book. Each gene represents a different recipe. The page with the chocolate cake recipe has a nice picture, but there is some information missing. The recipe says to preheat the oven and measure the flour, but the rest of the page is torn. So it is impossible to make the cake. We go ahead and serve our meal made from all the other recipes, but there is no chocolate cake even though this is a particularly important part of the meal.</p>
<p>The same is true for hereditary diseases. In this case, the body can make all the proteins it needs except one. In dysferlinopathy, which affects my family, the missing recipe is the protein that repairs the muscles of the arms and legs. Each hereditary disease has its own damaged page in its recipe book.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/580032/original/file-20240305-21577-nvf7ba.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/580032/original/file-20240305-21577-nvf7ba.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=426&fit=crop&dpr=1 600w, https://images.theconversation.com/files/580032/original/file-20240305-21577-nvf7ba.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=426&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/580032/original/file-20240305-21577-nvf7ba.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=426&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/580032/original/file-20240305-21577-nvf7ba.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=535&fit=crop&dpr=1 754w, https://images.theconversation.com/files/580032/original/file-20240305-21577-nvf7ba.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=535&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/580032/original/file-20240305-21577-nvf7ba.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=535&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A mutation can cause the absence of a protein that has its own function.</span>
<span class="attribution"><span class="source">(Camille Bouchard)</span>, <span class="license">Fourni par l'auteur</span></span>
</figcaption>
</figure>
<p>To be precise, an error in the DNA is called a mutation. There are different types of mutations. Some are caused by adding letters, like adding an ingredient to the recipe. This addition could lead to a delicious chocolate cake with strawberries, or to a cake that is no longer edible because we added motor oil to it.</p>
<p>Other mutations are caused by the removal (or elimination) of one or more letters (or ingredients), or by substitutions that replace one letter with another. All of these modifications can lead to favourable or non-impactful changes, such as the appearance of the first blue eyes in evolution, or the ability to breathe outside of water. But these modifications can also bring about unfavourable results, such as a hereditary disease or cancer.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/565888/original/file-20231214-19-3u3el2.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/565888/original/file-20231214-19-3u3el2.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/565888/original/file-20231214-19-3u3el2.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=616&fit=crop&dpr=1 600w, https://images.theconversation.com/files/565888/original/file-20231214-19-3u3el2.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=616&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/565888/original/file-20231214-19-3u3el2.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=616&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/565888/original/file-20231214-19-3u3el2.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=774&fit=crop&dpr=1 754w, https://images.theconversation.com/files/565888/original/file-20231214-19-3u3el2.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=774&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/565888/original/file-20231214-19-3u3el2.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=774&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">There are different types of mutations.</span>
<span class="attribution"><span class="source">(Camille Bouchard)</span>, <span class="license">Fourni par l'auteur</span></span>
</figcaption>
</figure>
<h2>Repairing DNA</h2>
<p>From a young age, I understood that my mother was sick due to the error of a gene, but that I would not develop the disease because my father did not have the same error. This is called a recessive disease, since there must be an error in the gene of each of the two parents in order for the disease to manifest. Other hereditary diseases are dominant, meaning that a mutation in the DNA passed down from just one parent is enough to impair the production of a protein.</p>
<p>As part of my research, I look at the DNA sequence of each dysferlinopathy patient to see where the error is.</p>
<p>To try to correct it, I use <a href="https://doi.org/10.3390/cells12040536">Prime editing</a>, a technique which makes it possible to cut the DNA near the mutation and rewrite the sequence correctly. Prime editing is a version of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4975809/">CRISPR-Cas9</a>, a technique that allows DNA to be cut at a particular location.</p>
<p>Prime editing uses a protein called Cas9, which occurs naturally in bacteria. This protein allows bacteria to destroy the DNA sequences of viruses that could infect them. The mission of the Cas9 protein is to recognize a sequence and cut it.</p>
<p>When we use Cas9 in our human cells, we attach it to another protein, which rewrites the DNA sequence based on a template. In other words, we give the cell an error-free sequence so that it can go ahead and manufacture the protein on its own. It’s a bit like recovering the original page of the recipe book so you can finally serve the chocolate cake.</p>
<h2>A step in the right direction</h2>
<p>So why aren’t we hearing about Prime editing, when it could be used to treat a variety of diseases? Because the technology is not yet fully developed. At the moment we are able to repair DNA directly in cells in the laboratory, but we lack the means to deliver the two large proteins (Cas9 and the one that rewrites) to the cells to be treated (for example, to the centre of the affected muscles).</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/565889/original/file-20231214-21-z2b726.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/565889/original/file-20231214-21-z2b726.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/565889/original/file-20231214-21-z2b726.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=434&fit=crop&dpr=1 600w, https://images.theconversation.com/files/565889/original/file-20231214-21-z2b726.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=434&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/565889/original/file-20231214-21-z2b726.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=434&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/565889/original/file-20231214-21-z2b726.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=546&fit=crop&dpr=1 754w, https://images.theconversation.com/files/565889/original/file-20231214-21-z2b726.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=546&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/565889/original/file-20231214-21-z2b726.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=546&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Prime editing is a technique being studied to correct mutations in different genes.</span>
<span class="attribution"><span class="source">(Camille Bouchard)</span>, <span class="license">Fourni par l'auteur</span></span>
</figcaption>
</figure>
<p>In other words, we have found the chocolate cake recipe, but it’s written on a page that is too large to fit in an email or put in an envelope. Many laboratories, including mine, are looking for an efficient and safe vehicle that will be able to deliver these proteins.</p><img src="https://counter.theconversation.com/content/219683/count.gif" alt="La Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Camille Bouchard received funding from the Jain Foundation and the Fondation du CHU de Québec.</span></em></p>Many people know someone with a genetic disease, but few understand how gene mutations work.Camille Bouchard, Étudiante au doctorat en médecine moléculaire (correction génétique de maladies héréditaires), Université LavalLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2196202024-01-18T16:38:26Z2024-01-18T16:38:26ZDNA from stone age chewing gum sheds light on diet and disease in Scandinavia’s ancient hunter-gatherers<figure><img src="https://images.theconversation.com/files/570142/original/file-20240118-27-aehxwa.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C464%2C352&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A mold cast of one of the chewed pitch pieces.</span> <span class="attribution"><span class="source">Verner Alexandersen</span>, <span class="license">Author provided</span></span></figcaption></figure><p>Some 9,700 years ago on an autumn day, a group of people were camping on the west coast of Scandinavia. They were hunter-gatherers that had been fishing, hunting and collecting resources in the area. </p>
<p>Some teenagers, both boys and girls, were chewing resin to produce glue, just after eating trout, deer and hazelnuts. Due to a severe gum infection (periodontitis), one of the teenagers had problems eating the chewy deer-meat, as well as preparing the resin by chewing it.</p>
<p>This snapshot of the Mesolithic period, just before Europeans started farming, comes from analysis of DNA left in the chewed resin that we have conducted, now <a href="https://www.nature.com/articles/s41598-023-48762-6">published in Scientific Reports</a>. </p>
<p>The location is now known as <a href="https://lup.lub.lu.se/search/publication/3c1fd58a-9495-4403-ab7d-d22104f2fafb">Huseby Klev</a>, situated north of Gothenburg (Göteborg), Sweden. <a href="https://www.cambridge.org/core/journals/antiquity/article/abs/wet-and-the-wild-followed-by-the-dry-and-the-tame-or-did-they-occur-at-the-same-time-diet-in-mesolithic-neolithic-southern-sweden/D91F7830FE704FD24DFAFB55E551039B">It was excavated</a> by archaeologists in the early 1990s, and yielded some 1,849 flint artefacts and 115 pieces of resin (mastic). The site has been radiocarbon dated to between 10,200 and 9,400 years ago, with one of the pieces of resin dated to 9,700 years ago.</p>
<p>Some of the resin has teeth imprints, indicating that children, actually teenagers, had been chewing them. Masticated lumps, often with imprints of teeth, fingerprints or both, are not uncommon to find in Mesolithic sites. </p>
<p>The pieces of resin we have analysed were made of <a href="https://www.nature.com/articles/s41467-019-13549-9">birch bark pitch</a>, which is known to have been used as an <a href="https://phys.org/news/2019-08-neanderthal-tool-making-simpler-previously-thought.html">adhesive substance in stone tool technology</a> from the Middle Palaeolithic onward. However, they were also chewed for recreational or medicinal purposes in traditional societies.</p>
<p>A variety of substances with similar properties, such as resins from coniferous trees, natural bitumen, and other plant gums, are known to have been used in analogous ways in many parts of the world.</p>
<h2>The power of DNA</h2>
<p>In some of the resin, half the <a href="https://www.nature.com/articles/s42003-019-0399-1">DNA extracted</a> was of human origin. This is a lot compared to what we often find in ancient bones and teeth. </p>
<p>It represents some of the oldest human genomes from Scandinavia. It has a particular ancestry profile common among Mesolithic hunter gatherers who once lived there. </p>
<p>Some of the resin contains male human DNA while others have female DNA. We think that teenagers of both sexes were preparing glue for use in tool making, such as attaching a stone axe to a wooden handle.</p>
<p>But what of the other half of the DNA that was of non-human origin? Most of this DNA is from organisms such as bacteria and fungi that have lived in the mastic since it was discarded 9,700 years ago. But some of it was from bacteria living in the human that chewed it, along with material the human had been chewing on before they put the birch bark pitch in their mouths.</p>
<p>Analysing all this DNA is a demanding task and treads new ground. We had to both adapt existing computing tools and also develop some new analytical strategies. As such, this work has become the starting point for developing a new workflow for this kind of analysis. </p>
<p>This includes mining the DNA using different strategies to characterise it, trying to piece together short DNA fragments into longer ones and using machine learning techniques to work out which DNA fragments belong to pathogens (harmful microorganisms). It also involves comparing the data to what we see in the mouths of modern people with <a href="https://www.ncbi.nlm.nih.gov/books/NBK551699/">tooth decay (caries)</a> and periodontitis.</p>
<h2>Higher organisms</h2>
<p>Naturally, we found the kind of bacteria that would be expected in an oral microbiome, the range of naturally occurring microorganisms found in the mouth. We also found traces of bacteria implicated in conditions such as tooth decay or caries (<em>Streptococcus mutans</em>), and systemic diseases such as Hib disease and endocarditis. There were also bacteria that can cause abscesses. </p>
<p>Although these pathogenic microorganisms were present at an elevated frequency, they were not clearly above the level expected for a healthy oral microbiome. There is thus no conclusive evidence that members of the group suffered from diseases these microorganisms are associated with. </p>
<p>What we did find, however, was an abundance of bacteria associated with serious gum disease – <a href="https://www.mayoclinic.org/diseases-conditions/periodontitis/symptoms-causes/syc-20354473">periodontitis</a>. When we applied a <a href="https://www.ibm.com/topics/machine-learning">machine learning</a> strategy (in this case, a technique called <a href="https://www.ibm.com/topics/random-forest">Random Forest modelling</a>) we reached the conclusion that the girl who chewed one of the pieces of resin had probably suffered from periodontitis – with more than a 75% probability.</p>
<p>We also found DNA from larger organisms than just bacteria. We found DNA for red deer, brown trout and hazelnuts. This DNA probably came from material the teenagers had been chewing before they put the birch pitch in their mouths. </p>
<p>However, we need to be a little bit cautious because exactly what we find is also dependent on the comparison data that we have. As genomes from eukaryotic organisms – the group that includes plants and animals – <a href="https://www.ncbi.nlm.nih.gov/books/NBK9846/">are larger and more complex</a> than those from microorganisms, it is more complicated to assemble a eukaryotic genome of high quality. </p>
<p>There are fewer eukaryotic genomes in the samples of resin, and they are of lower quality. This means that our brown trout, for example, may not actually be a brown trout, but we at least feel certain it is from the salmon family.</p>
<p>We also found a lot of fox DNA, but this is harder to interpret. Fox meat may have been a part of the diet, but these teenagers could also have chewed on tendons and fur from foxes for use in textiles. Alternatively, the fox DNA could even be from territorial marking and got into the resin after it was spat out.</p>
<p>However, what we have learned for sure represents a big step in understanding these fascinating records of human culture from the Stone Age. As we analyse more of these, even more surprises could emerge.</p><img src="https://counter.theconversation.com/content/219620/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Anders Götherström receives funding from: the Swedish Research Council (2019-00849_VR), Riksbankens Jubileumsfond (P16-0553:1)</span></em></p><p class="fine-print"><em><span>Emrah Kırdök 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>Genetic analysis reveals one of the teenagers probably had advanced gum disease.Anders Götherström, Professor in Molecular Archaeology, Department of Archaeology and Classical Studies, Stockholm UniversityEmrah Kırdök, Assistant Professor, Department of Biotechnology, Mersin 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>
<figcaption>
<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>
</figcaption>
</figure>
<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>
<figcaption>
<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>
</figcaption>
</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>
<figure class="align-center ">
<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">
<figcaption>
<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">
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<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>
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</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>
<hr>
<p>
<em>
<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/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>
<hr>
<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>
<hr>
<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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</em>
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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/2048882023-05-04T19:06:29Z2023-05-04T19:06:29ZReconstructing ancient bacterial genomes can revive previously unknown molecules – offering a potential source for new antibiotics<figure><img src="https://images.theconversation.com/files/523906/original/file-20230502-2182-swsnio.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C8256%2C5499&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Ancient DNA preserved in the tooth tartar of human fossils encodes microbial metabolites that could be the next antibiotic.</span> <span class="attribution"><a class="source" href="https://www.eurekalert.org/multimedia/983784?">Werner/Siemens Foundation</a></span></figcaption></figure><p>Microorganisms – in particular bacteria – are skillful chemists that can produce an impressive diversity of chemical compounds known as <a href="https://theconversation.com/nature-is-the-worlds-original-pharmacy-returning-to-medicines-roots-could-help-fill-drug-discovery-gaps-176963">natural products</a>. These metabolites provide the microbes major evolutionary advantages, such as allowing them to interact with one another or their environment and helping defend against different threats. Because of the diverse functions bacterial natural products have, many have been <a href="https://doi.org/10.1021/acs.jnatprod.5b01055">used as medical treatments</a> such as antibiotics and anti-cancer drugs.</p>
<p>The microbial species alive today represent only a tiny fraction of the vast diversity of microbes that have inhabited Earth over the past <a href="https://theconversation.com/were-viruses-around-on-earth-before-living-cells-emerged-a-microbiologist-explains-197880">3 billion years</a>. Exploring this microbial past presents exciting opportunities to recover some of their lost chemistry. </p>
<p>Directly studying these metabolites in archaeological samples is virtually impossible because of their <a href="https://doi.org/10.1007/s11306-017-1270-3">poor preservation</a> over time. However, reconstructing them using the genetic blueprints of long-dead microbes could provide a path forward. </p>
<p>We are a team of <a href="https://scholar.google.com/citations?user=cDFcc3cAAAAJ&hl=en">anthropologists</a>, <a href="https://scholar.google.de/citations?user=trnMQ7MAAAAJ&hl=en">archaeogeneticists</a> and <a href="https://scholar.google.com/citations?user=26MgwRgAAAAJ&hl=en">biochemists</a> who study ancient microbes. By <a href="https://www.science.org/doi/10.1126/science.adf5300">generating previously unknown chemical compounds</a> from the reconstructed genomes of ancient bacteria, our newly published research provides a proof of concept for the potential use of fossil microbes as a source of new drugs.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/524480/original/file-20230504-17-ivzxrf.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Researcher weighing tooth fossil on a scale" src="https://images.theconversation.com/files/524480/original/file-20230504-17-ivzxrf.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/524480/original/file-20230504-17-ivzxrf.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=565&fit=crop&dpr=1 600w, https://images.theconversation.com/files/524480/original/file-20230504-17-ivzxrf.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=565&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/524480/original/file-20230504-17-ivzxrf.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=565&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/524480/original/file-20230504-17-ivzxrf.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=710&fit=crop&dpr=1 754w, https://images.theconversation.com/files/524480/original/file-20230504-17-ivzxrf.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=710&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/524480/original/file-20230504-17-ivzxrf.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=710&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">A single ancient tooth preserves the genomes of millions of ancient bacteria.</span>
<span class="attribution"><span class="source">Felix Wey/Werner Siemens Foundation</span></span>
</figcaption>
</figure>
<h2>Reconstructing ancient genomes</h2>
<p>The cellular machinery producing bacterial natural products is encoded in genes that are typically in close proximity to one another, forming what are called <a href="https://doi.org/10.1016/j.tim.2016.07.006">biosynthetic gene clusters</a>. Such genes are difficult to detect and reconstruct from ancient DNA because very old genetic material breaks down over time, fragmenting into thousands or even millions of pieces. The end result is numerous tiny DNA fragments <a href="https://doi.org/10.1038/s43586-020-00011-0">less than 50 nucleotides long</a> all mixed together like a jumbled jigsaw puzzle.</p>
<p>We sequenced billions of such ancient DNA fragments, then improved a bioinformatic process called <a href="https://doi.org/10.1007/s40484-019-0166-9">de novo assembly</a> to digitally order the ancient DNA fragments in stretches of up to 100,000 nucleotides long – a 2,000-fold improvement. This process allowed us to identify not only what genes were present, but also their order in the genome and the ways they differ from bacterial genes known today – key information to uncovering their evolutionary history and function. </p>
<p>This method allowed us to take an unprecedented look at the genomes of microbes living up to 100,000 years ago, including species not known to exist today. Our findings push back the <a href="https://doi.org/10.1038/s41586-021-03532-0">previously oldest</a> <a href="https://doi.org/10.1186/s40168-021-01132-8">reconstructed microbial genomes</a> by more than 90,000 years.</p>
<p>In the microbial genomes we reconstructed from DNA extracted from ancient tooth tartar, we found a gene cluster that was shared by a high proportion of Neanderthals and anatomically modern humans living during the <a href="https://www.britannica.com/event/Stone-Age/Middle-Paleolithic">Middle and Upper Paleolithic</a> that lasted from 300,000 to 12,000 years ago. This cluster bore the <a href="https://doi.org/10.1038/s43586-020-00011-0">molecular hallmarks of very ancient DNA</a> and belonged to the bacterial genus <em>Chlorobium</em>, a group of green sulfur bacteria capable of photosynthesis.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/524154/original/file-20230503-26-5xqprb.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Chemical structure of paleofurans produced using ancient microbial DNA." src="https://images.theconversation.com/files/524154/original/file-20230503-26-5xqprb.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/524154/original/file-20230503-26-5xqprb.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=280&fit=crop&dpr=1 600w, https://images.theconversation.com/files/524154/original/file-20230503-26-5xqprb.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=280&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/524154/original/file-20230503-26-5xqprb.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=280&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/524154/original/file-20230503-26-5xqprb.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=351&fit=crop&dpr=1 754w, https://images.theconversation.com/files/524154/original/file-20230503-26-5xqprb.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=351&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/524154/original/file-20230503-26-5xqprb.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=351&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 paleofurans were produced from ancient microbial DNA.</span>
<span class="attribution"><span class="source">Pierre Stallforth</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>We inserted a synthetic version of this gene cluster into a “modern” bacterium called <em>Pseudomona protegens</em> so it could produce the chemical compounds encoded in the ancient genes. Using this method, we were able to isolate two previously unknown compounds we named <a href="https://www.science.org/doi/10.1126/science.adf5300">paleofuran A and B</a> and determine their chemical structure. Resynthesizing these molecules in the lab from scratch confirmed their structure and allowed us to produce larger quantities for further analysis.</p>
<p>By reconstructing these ancient compounds, our findings highlight how archaeological samples could serve as new sources of natural products. </p>
<h2>Mining ancient natural products</h2>
<p>Microbes are constantly evolving and adapting to their surrounding environment. Because the environments they inhabit today differ from those of their ancestors, microbes today likely produce different natural products than ancient microbes from tens of thousands of years ago.</p>
<p>As recently as <a href="https://www.doi.org/10.1007/978-1-4613-1145-4_1">25,000 to 10,000 years ago</a>, the Earth underwent a major climate shift as it transitioned from the colder and more volatile <a href="https://www.britannica.com/science/Pleistocene-Epoch">Pleistocene Epoch</a> to the warmer and more temperate <a href="https://www.britannica.com/science/Holocene-Epoch">Holocene Epoch</a>. Human lifestyles also dramatically changed over this transition as people began living outside of caves and increasingly experimented with food production. These changes brought them into contact with different microbes through agriculture, animal husbandry and their new built environments. Studying Pleistocene-era bacteria may yield insights into bacterial species and biosynthetic genes no longer associated with humans today, and perhaps even microbes that have gone extinct.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/JfX06NINZpk?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Changes in human lifestyles changed our genomes.</span></figcaption>
</figure>
<p>While the amount of data collected by scientists on biological organisms has exponentially increased over the past few decades, the <a href="https://theconversation.com/antibiotic-resistance-is-at-a-crisis-point-government-support-for-academia-and-big-pharma-to-find-new-drugs-could-help-defeat-superbugs-169443">number of new antibiotics has stagnated</a>. This is particularly problematic when bacteria are able to evade existing antibiotic treatments faster than researchers can develop new ones. </p>
<p>By reconstructing microbial genomes from archaeological samples, scientists can tap into the hidden diversity of natural products that would have otherwise been lost over time, increasing the number of potential sources from which they can discover new drugs.</p>
<h2>Scaling up ancient molecules</h2>
<p>Our study has shown that it is possible to access natural products from the past. To tap into the vast diversity of chemical compounds encoded in ancient DNA, we now need to streamline our methodology to be less labor-intensive. </p>
<p>We are currently optimizing and automating our process to identify biosynthetic genes in ancient DNA more quickly and reliably. We are also implementing robotic liquid handling systems to complete the time-consuming pipetting and bacterial cultivation steps in our methods. Our goal is to scale up the process to be able to translate a vast amount of data on ancient microbes into the discovery of new therapeutic agents. </p>
<p>Although we can recreate ancient molecules, their biological and ecological roles are difficult to decipher. Since the bacteria that originally produced these compounds no longer exist, we cannot culture or genetically manipulate them. Further study will need to rely on similar bacteria that can be found today. Whether or not the functions of these compounds have remained the same in the modern relatives of ancient microbes remains to be tested. Although the original functions of these compounds for ancient microbes may be unknown, they still have the potential to be repurposed to treat modern diseases.</p>
<p>Ultimately, we aim to shed new light on microbial evolution and fight the current antibiotic crisis by providing a new time axis for antibiotic discovery.</p><img src="https://counter.theconversation.com/content/204888/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Christina Warinner receives funding from the Werner Siemens Foundation, the Francis Goelet Charitable Trust, the European Research Council, the United States National Science Foundation, and the Deutsche Forschungsgemeinschaft. She is affiliated with the Max Planck Institute for Evolutionary Anthropology, the Leibniz Institute of Natural Product Research and Infection Biology (Leibniz-HKI), and the Biological Faculty of Friedrich Schiller University Jena. </span></em></p><p class="fine-print"><em><span>Alexander Hübner receives funding from the Werner Siemens Foundation, the European Research Council, and the Deutsche Forschungsgemeinschaft. He is affiliated with with the Leibniz Institute of Natural Product Research and Infection Biology (Leibniz-HKI).</span></em></p><p class="fine-print"><em><span>Pierre Stallforth receives funding from the Werner Siemens Foundation, the Deutsche Forschungsgemeinschaft, and the Leibniz Association. He is affiliated with with the Leibniz Institute of Natural Product Research and Infection Biology (Leibniz-HKI) and the Friedrich Schiller University, Jena, Germany.</span></em></p>Ancient microbes likely produced natural products their descendants today do not. Tapping into this lost chemical diversity could offer a potential source of new drugs.Christina Warinner, Associate Professor of Anthropology, Harvard UniversityAlexander Hübner, Postdoctoral Researcher in Archaeogenetics, Max Planck Institute for Evolutionary AnthropologyPierre Stallforth, Professor of Bioorganic Chemistry and Paleobiotechnology, Friedrich-Schiller-Universität JenaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2043402023-04-24T21:42:07Z2023-04-24T21:42:07ZCanadian science pioneers’ role in the Human Genome Project shows why it’s crucial to fund research<figure><img src="https://images.theconversation.com/files/522693/original/file-20230424-1269-xtr2u1.jpg?ixlib=rb-1.1.0&rect=149%2C17%2C1623%2C991&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The research and vision of Canadian scientists were key foundations of the Human Genome Project. Today, lack of funding threatens discovery research in Canada.</span> <span class="attribution"><span class="source">(Pixabay)</span></span></figcaption></figure><p>On April 25, the world will celebrate <a href="https://www.genome.gov/dna-day">DNA Day</a>, marking two events: the 70th anniversary of the <a href="https://www.cam.ac.uk/stories/DNA-structure-discovery-cambridge-70th-anniversary">discovery of the double helix</a> and the 20th anniversary of the <a href="https://www.genome.gov/human-genome-project">Human Genome Project</a>, which sequenced humans’ genetic blueprint for the first time.</p>
<p>For the Human Genome Project, Canadians were at the forefront. </p>
<p>The distinguished Canadian medical geneticist Charles Scriver of McGill University, <a href="https://healthenews.mcgill.ca/in-memoriam-charles-r-scriver/">who recently passed away</a>, convinced the Howard Hughes Medical Institute in the United States in 1986 to bring together the parties who could fund and execute the Human Genome project. This objective has been acknowledged as prescient. </p>
<p>The meeting was attended by Nobel Prize winners <a href="https://www.nobelprize.org/prizes/chemistry/1980/gilbert/biographical/">Walter Gilbert</a> and <a href="https://www.nobelprize.org/prizes/medicine/1962/watson/biographical/">James Watson</a>, and is described as a major catalyst for the Human Genome Project in <em><a href="https://books.google.ca/books/about/The_Book_of_Man.html?id=ys5qAAAAMAAJ&redir_esc=y">The Book of Man: The Human Genome Project and the Quest to Discover Our Genetic Heritage</a></em>.</p>
<h2>From inspiration to sequencing the genome</h2>
<p>Scriver was well aware of the <a href="https://www.ncbi.nlm.nih.gov/books/NBK234203/">significance sequencing the human genome</a> would have on clinical genetics and the impact it would have on the health of patients, including identifying genetic causes of diseases.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/-hryHoTIHak?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">The Human Genome Project.</span></figcaption>
</figure>
<p>To move forward from Scriver’s inspiration, a proof of principle project was needed. This was provided by the discovery of the gene for cystic fibrosis (CF) by Lap-Chee Tsui and Jack Riordan, who were then at the University of Toronto, and Francis Collins, then at the University of Michigan. In 1990 they indicated: </p>
<blockquote>
<p>“<a href="https://doi.org/10.1080/21548331.1990.11704019">More broadly, the cloning of the CF gene provides a fast start in the international effort to clone and map the entire human genome</a>”</p>
</blockquote>
<p>These pioneers performed the very challenging task of <a href="https://doi.org/10.1126/science.2475911">identifying the gene mutation in unaffected people (those with a single mutated gene)</a>. CF is a recessive genetic condition, meaning a person must inherit two mutated genes — one from each parent — to develop the disease. Today as a result of Canadian discovery science, <a href="https://www.cysticfibrosis.ca/registry/2021AnnualDataReport.pdf">patients with cystic fibrosis have a median age of survival of 57 years</a>, compared to 35.9 years in 2001.</p>
<p>One of these pioneers went on to lead the even more challenging Human Genome Project. Collins received Canada’s Gairdner International Award in 2002 for “<a href="https://www.gairdner.org/winner/francis-s-collins">his outstanding leadership in the Human Genome Project and particularly for the international effort to map and sequence human and other genomes</a>.”</p>
<p>This was a rare occurrence of a scientist winning a second Gairdner International Award, with Collins receiving his first Gairdner for the CF gene discovery, along with Tsui and Riordan, in 1990.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/solving-the-puzzle-of-cystic-fibrosis-and-its-treatments-is-a-nobel-prize-worthy-breakthrough-175335">Solving the puzzle of cystic fibrosis and its treatments is a Nobel Prize-worthy breakthrough</a>
</strong>
</em>
</p>
<hr>
<p>Another Gairdner International award winner recognized for leadership in the Human Genome Project is <a href="https://www.gairdner.org/winner/james-d-watson">Watson</a>. This year’s DNA Day will celebrate the 70th anniversary of the double helix, for which Watson was later recognized with a <a href="https://www.nobelprize.org/prizes/medicine/1962/summary/">Nobel prize in 1962</a>.</p>
<p>It was belatedly recognized that the experimental data for the double helix was actually an <a href="https://www.nobelprize.org/prizes/medicine/1962/speedread/">X-ray of a crystal of DNA by the late Rosalind Franklin</a>.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/closing-the-gender-gap-in-the-life-sciences-is-an-uphill-struggle-112920">Closing the gender gap in the life sciences is an uphill struggle</a>
</strong>
</em>
</p>
<hr>
<p>The consequences of the discovery of DNA and the sequencing of the Human Genome have been monumental for health research globally. As <a href="https://doi.org/10.1056/NEJMp2030694">summarized in 2021 by Collins</a>, the genes for over 5,000 rare diseases were discovered as well as insight into Alzheimer’s disease, schizophrenia, heart disease and cancer.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/HkRqgeLE_fs?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Charles Scriver, Canadian Medical Hall of Fame laureate 2001.</span></figcaption>
</figure>
<p>Astonishingly, it is through DNA that all of us can follow the trajectory of our families through genetic genealogy. Remarkably, the Nobel Prize in 2022 was awarded to Svante Pääbo of the Max Planck Institute in Leipzig, Germany for the <a href="https://www.nobelprize.org/prizes/medicine/2022/press-release/">new field of paleogenomics</a>. His discoveries involving the intricate sequencing of genomic DNA from our extinct human ancestors led to the discovery of a new branch of human ancestors now known as the Denisovans.</p>
<p>Today, the genetic genealogy of modern and ancient humans has been extended through the analysis of the DNA of over 7,000 different genomes. This new study has defined the <a href="https://doi.org/10.1126%2Fscience.abi8264">geographic location of the trajectory of our ancestors</a> extending to over 800,000 years ago! DNA Day is a worthy celebration.</p>
<h2>Can DNA Day be of significance in Canada?</h2>
<p>The dedication of our accomplished discovery researchers Tsui, Riordan and Scriver inspired and led to the Human Genome Project. However, the project did not involve Canada. The major reason for this was funding. </p>
<p>The Human Genome Project was largely funded by the U.S. National Institutes of Health to the labs of <a href="https://doi.org/10.1073/pnas.042692499">Robert Waterston at Washington University and Eric Lander at MIT</a>. In addition, John Sulston was funded in the United Kingdom as part of the trio who actually sequenced the human genome.</p>
<p>Journalist and political commentator Paul Wells recently lamented the <a href="https://paulwells.substack.com/p/building-pyramids-from-the-top-down">decades of deteriorating funding for Canadian discovery research</a>. In 2019, Canada was ranked 18th globally in researchers per 1,000 population down from its 8th rank in 2011. </p>
<p>Without funding improvements, Canada will continue to lose the talent it was once proud to have. This loss is unsustainable for meeting the challenges of future pandemics, climate change and the continuing ravages of disease.</p>
<p>Scriver, Tsui and Riordan should inspire pride for the value of discovery research in Canada that globally saves human lives. Canada should remember their legacy on DNA day.</p>
<p><em>John Bergeron gratefully acknowledges Kathleen Dickson as co-author.</em></p><img src="https://counter.theconversation.com/content/204340/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>John Bergeron 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>On DNA Day, Canada should be inspired by the lifesaving discoveries of its researchers. However, lack of funding threatens Canadian researchers’ ability to meet the challenges of the future.John Bergeron, Emeritus Robert Reford Professor and Professor of Medicine, McGill UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2024902023-04-14T12:31:04Z2023-04-14T12:31:04ZDNA study opens a window into African civilisations that left a lasting legacy<figure><img src="https://images.theconversation.com/files/519034/original/file-20230403-14-m699gl.jpg?ixlib=rb-1.1.0&rect=9%2C0%2C6473%2C4325&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Stone obelisks stand tall in Aksum, Ethiopia. This city was once the capital of a kingdom spanning northeast Africa and the Arabian peninsula.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/ancient-monolith-stone-obelisk-symbol-old-1831447870">Shutterstock / Artist</a></span></figcaption></figure><p>Pre-colonial African history is alive with tales of civilisations rising and falling and of different cultures intermingling across the continent. We have now shed more light on some of these societies using the science of genetics. </p>
<p>In a study <a href="https://www.science.org/doi/10.1126/sciadv.abq2616">published in Science Advances</a>, my co-authors and I used DNA information from people from the present-day continent to shed light on important civilisations that existed before colonialism. Genetic information from cheek swabs was extracted by machines. Once the sequence of “letters” in the DNA code had been read, or sequenced, we could use computers to compare genetic differences and similarities between the populations in the study.</p>
<p>One striking result concerned two ethnic groups in the north of present-day Cameroon, in west-central Africa, the Kanuri and Kotoko peoples. We found that these two groups were descended from three ancestral populations. </p>
<p>These ancestral groups most resembled people now living in coastal regions of west Africa as well as in parts of east Africa such as Ethiopia and populations living today in north Africa and the Levant. The populations intermixed – had children together – roughly 600 years ago. But what caused them to migrate thousands of kilometres across a desert into northern Cameroon? </p>
<figure class="align-left ">
<img alt="Map of the Kanem-Bornu empire" src="https://images.theconversation.com/files/519336/original/file-20230404-28-zarx0t.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/519336/original/file-20230404-28-zarx0t.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=615&fit=crop&dpr=1 600w, https://images.theconversation.com/files/519336/original/file-20230404-28-zarx0t.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=615&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/519336/original/file-20230404-28-zarx0t.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=615&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/519336/original/file-20230404-28-zarx0t.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=773&fit=crop&dpr=1 754w, https://images.theconversation.com/files/519336/original/file-20230404-28-zarx0t.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=773&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/519336/original/file-20230404-28-zarx0t.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=773&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The Kanem-Bornu empire at its greatest extent.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Afrika-Kanem-Bornu.png">Tourbillon / Wikipedia Project</a></span>
</figcaption>
</figure>
<p>We think the answer is the <a href="https://www.vincenthiribarren.com/pdf/Hiribarren_-_2016_-_Kanem-Bornu.pdf">Kanem-Bornu empire</a>, a civilisation that existed for over 1,000 years – beginning around 700 AD. At its height, the empire spanned what is now northern Cameroon, northern Nigeria, Chad, Niger and southern Libya. It operated vast trade networks across the Sahara and attracted populations from every direction.</p>
<p>This example highlights how our genomes hold information about major events of the past. Merchants travelling along trade routes or the formation of empires from smaller political units can leave footprints in our DNA. <a href="https://www.science.org/doi/full/10.1126/science.1243518">Previous work</a> <a href="https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1001373">shows</a> that <a href="https://www.science.org/doi/10.1126/science.aay6826">the Roman empire</a>, the <a href="https://www.frontiersin.org/articles/10.3389/fgene.2021.735786/full">Mongol empire</a>, and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4267745/">Silk Road trade</a> probably all left lasting legacies in the genomes of modern-day people across Eurasia.</p>
<h2>Hidden in the genome</h2>
<p>We analysed 1,300 newly collected genomes of people from across Africa. They came from 150 ethnic groups within five countries. We collaborated with anthropologists, archaeologists and linguists from Africa and elsewhere. They helped us understand the historical context of these events.</p>
<figure class="align-center ">
<img alt="Mandara mountains" src="https://images.theconversation.com/files/519315/original/file-20230404-982-x059iv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/519315/original/file-20230404-982-x059iv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=360&fit=crop&dpr=1 600w, https://images.theconversation.com/files/519315/original/file-20230404-982-x059iv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=360&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/519315/original/file-20230404-982-x059iv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=360&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/519315/original/file-20230404-982-x059iv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=452&fit=crop&dpr=1 754w, https://images.theconversation.com/files/519315/original/file-20230404-982-x059iv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=452&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/519315/original/file-20230404-982-x059iv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=452&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The Kotoko and Kanuri people live in northern Cameroon and Nigeria. The photo shows a landscape in the Mandara mountains, near the border of the two countries.</span>
<span class="attribution"><span class="source">Scott MacEachern</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>African genome data <a href="https://www.annualreviews.org/doi/10.1146/annurev-biodatasci-102920-%20112550?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed">is underrepresented</a> compared with that from other world regions. This means that lots of genetic diversity – or variety – in the DNA of populations is probably being missed by scientists. </p>
<p>Studying genetic diversity has many potential uses – such as understanding risks to health and developing new treatments for disease. Our group was concerned with genetic diversity as a window into the past.</p>
<h2>Dating events</h2>
<p>We modelled a person’s genome as a mixture of segments of DNA inherited from their ancestors. If a person had DNA segments closely matching two groups of people – for example, Europeans and west Africans – it suggested that this person descended from mixing between those two groups. </p>
<figure class="align-center ">
<img alt="Great Zimbabwe" src="https://images.theconversation.com/files/519299/original/file-20230404-20-1aikqn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/519299/original/file-20230404-20-1aikqn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/519299/original/file-20230404-20-1aikqn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/519299/original/file-20230404-20-1aikqn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/519299/original/file-20230404-20-1aikqn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/519299/original/file-20230404-20-1aikqn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/519299/original/file-20230404-20-1aikqn.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">Mysteries remain about other civilisations not studied in the latest work. These are buildings from Great Zimbabwe, a medieval city in Southern Africa.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/great-zimbabwe-medieval-city-southeastern-hills-1048631507">evenfh / Shutterstock</a></span>
</figcaption>
</figure>
<p>Present-day human groups that were formed from a recent mixture of Europeans and west Africans should have long sections of DNA from both populations. Those ancestral DNA segments get shorter as the genetic material of their descendants is shuffled with each new generation. </p>
<p>This provides a way of dating when mixture events took place. The longer the DNA segments matching, for example, west Africans or Europeans, the more recent the mixture event was.</p>
<h2>Peace treaty</h2>
<p>Another historical event we found evidence for was the Arab expansion in Africa. This began in the seventh century, when separate Arab armies travelling south along the Levantine coast and north from Medina in today’s Saudi Arabia crossed the Sinai desert and conquered Egypt.</p>
<figure class="align-left ">
<img alt="The kingdom of Makuria at its peak around 960 AD." src="https://images.theconversation.com/files/519342/original/file-20230404-20-2sx8ay.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/519342/original/file-20230404-20-2sx8ay.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=1255&fit=crop&dpr=1 600w, https://images.theconversation.com/files/519342/original/file-20230404-20-2sx8ay.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=1255&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/519342/original/file-20230404-20-2sx8ay.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=1255&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/519342/original/file-20230404-20-2sx8ay.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1577&fit=crop&dpr=1 754w, https://images.theconversation.com/files/519342/original/file-20230404-20-2sx8ay.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1577&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/519342/original/file-20230404-20-2sx8ay.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1577&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The kingdom of Makuria at its peak around 960 AD.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:The_Kingdom_of_Makuria_at_its_peak.jpg">Le Gabrie</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>In Sudan at this time, the Kingdom of Makuria <a href="http://nubianmonasteries.uw.edu.pl/about/">ruled along the Nile river</a>. Makuria signed a peace treaty with the Egyptian Arabs in the <a href="https://bmcr.brynmawr.edu/2003/2003.01.16/">middle of the seventh century</a> that lasted almost 700 years.</p>
<p>The majority of mixing between these two ancestral groups, one closely related to Arabs and the other to Sudanese, dates to after the peace treaty began breaking down. This in turn coincided with the decline and eventual collapse of Makuria itself, which would have allowed Arab groups to continue down the Nile into Sudan. </p>
<p>But we also found evidence of earlier migrations into Africa from the Arabian peninsula, which occurred by sea. This intermixing coincided in time with the <a href="https://education.nationalgeographic.org/resource/kingdom-aksum/">Kingdom of Aksum</a>, located in northeast Africa and southern Arabia, during the first millennium AD.</p>
<figure class="align-center ">
<img alt="The throne hall of Old Dongola in Sudan, capital of the Makuria kingdom" src="https://images.theconversation.com/files/519067/original/file-20230403-20-eo26qk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/519067/original/file-20230403-20-eo26qk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=900&fit=crop&dpr=1 600w, https://images.theconversation.com/files/519067/original/file-20230403-20-eo26qk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=900&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/519067/original/file-20230403-20-eo26qk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=900&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/519067/original/file-20230403-20-eo26qk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1131&fit=crop&dpr=1 754w, https://images.theconversation.com/files/519067/original/file-20230403-20-eo26qk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1131&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/519067/original/file-20230403-20-eo26qk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1131&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The throne hall of Old Dongola in Sudan, capital of the Makuria kingdom.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/throne-hall-building-old-dongola-deserted-2118567158">Matyas Rehak / Shutterstock</a></span>
</figcaption>
</figure>
<p>Aksum was once considered <a href="https://link.springer.com/chapter/10.1007/978-1-137-11786-%201_2#:%7E:text=The%20Persian%20prophet%20Mani%2C%20who,the%20kingdom%20of%20the%20Chi%20nese.">one of the world’s four great powers</a>, alongside contemporary empires in China, Persia and Rome.</p>
<figure class="align-center ">
<img alt="Map of the Kingdom of Aksum." src="https://images.theconversation.com/files/519565/original/file-20230405-26-hndwxk.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/519565/original/file-20230405-26-hndwxk.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=540&fit=crop&dpr=1 600w, https://images.theconversation.com/files/519565/original/file-20230405-26-hndwxk.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=540&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/519565/original/file-20230405-26-hndwxk.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=540&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/519565/original/file-20230405-26-hndwxk.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=679&fit=crop&dpr=1 754w, https://images.theconversation.com/files/519565/original/file-20230405-26-hndwxk.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=679&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/519565/original/file-20230405-26-hndwxk.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=679&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Map of the Kingdom of Aksum.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Kingdom_of_Aksum_Map.png">Newslea Staff / Wikipedia</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<h2>The expansion of Bantu-speaking peoples</h2>
<p>Genetic studies have also found evidence of a continent-wide migration known as the expansion of Bantu-speaking peoples. “Bantu” is a language group, now spoken by around <a href="https://www.britannica.com/art/Bantu-languages">one-quarter of Africans</a>.</p>
<p>There has been debate about whether the Bantu languages spread largely as a transmission of culture, or whether large-scale migration was involved. The latest research shows that the latter explanation is the likeliest. This migration started in a small area of western Cameroon roughly 4,000 years ago, before rapidly spreading south and east. It covered more than 4,000 kilometres in less than 2,000 years. </p>
<p>Bantu speakers mixed with local groups, <a href="https://www.science.org/doi/full/10.1126/science.aal1988">changing patterns of genetic diversity in Africa</a> forever. We showed that migrations not only occurred to the south and east of Cameroon, but also to the west. Why so much movement took place at this time is unknown, but climate change may have played a role.</p>
<p>It’s vital that scientists analyse more DNA from genomes of African people. As we do so, it will undoubtedly reveal an intricate picture of the continent’s rich past.</p><img src="https://counter.theconversation.com/content/202490/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Nancy Bird receives funding from NERC. </span></em></p>DNA analysis sheds light on important societies within Africa that existed before colonialism.Nancy Bird, Postdoctoral research associate, UCLLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2009832023-03-08T12:06:26Z2023-03-08T12:06:26ZHuman genome editing offers tantalizing possibilities – but without clear guidelines, many ethical questions still remain<figure><img src="https://images.theconversation.com/files/513790/original/file-20230306-28-k1tc0y.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1936%2C1547&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">DNA editing has the capacity to treat many diseases, but how to do this safely and equitably remains unclear.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/molecules-illustration-royalty-free-image/1148113002">KTSDESIGN/Science Photo Library via Getty Images</a></span></figcaption></figure><p><a href="https://royalsociety.org/science-events-and-lectures/2023/03/2023-human-genome-editing-summit/">The Third International Summit on Human Genome Editing</a>, a three-day conference organized by the Royal Society, the U.K. Academy of Medical Sciences, the U.S. National Academies of Sciences and Medicine and The World Academy of Sciences, was held this week in March 2023 at the Francis Crick Institute in London. Scientists, bioethicists, physicians, patients and others gathered to discuss the latest developments on this technology that lets researchers modify DNA with precision. And a major topic at the summit was <a href="https://royalsociety.org/-/media/events/2023/03/human-genome-editing-summit/third-international-summit-on-human-genome-editing-programme-booklet.pdf?la=en-GB&hash=16DB894FBD02A549B2F090D575C3E92D">how to enforce</a> research policies and ethical principles for human genome editing.</p>
<p>One of the first agenda items was how to regulate human genome editing in China in light of its <a href="https://theconversation.com/crispr-babies-raise-an-uncomfortable-reality-abiding-by-scientific-standards-doesnt-guarantee-ethical-research-108008">misuse in 2018</a>, when scientists modified the DNA of two human embryos before birth to have resistance against HIV infection. The controversy stems from the fact that because the technology is relatively early in its development, and its potential risks have not been reduced or eliminated, editing human embryos in ways they could pass on to their own offspring could lead to a variety of known and unknown adverse complications. The <a href="https://www.statnews.com/2023/03/06/genome-editing-summit-experts-worry-rule-changes-in-china-fall-short/">summit speakers noted</a> that while China has updated its guidelines and laws on human genome editing, it failed to address privately funded research – an issue other countries also face. Many countries, including the U.S., <a href="https://doi.org/10.1038/d41586-023-00625-w">do not have sufficiently robust regulatory frameworks</a> to prevent a repeat of the 2018 scandal.</p>
<p>We are a <a href="https://www.rit.edu/hudsonlab/">biochemist</a> and a <a href="https://www.rit.edu/directory/grssbi-gary-skuse">geneticist</a> who teach and conduct research in genomics and ethics at the Rochester Institute of Technology. As in our classrooms, debate about genome editing continues in the field.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/E8vi_PdGrKg?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Listening to different perspectives about CRISPR could lead to more balanced discussions about how to regulate it.</span></figcaption>
</figure>
<h2>What is genome editing?</h2>
<p>The <a href="https://theconversation.com/the-human-genome-project-pieced-together-only-92-of-the-dna-now-scientists-have-finally-filled-in-the-remaining-8-176138">human genome</a> typically consists of 23 pairs of chromosomes made of approximately 3.2 billion nucleotides – the building blocks of DNA. There are four nucleotides that make up DNA: adenine (A), thymine (T), guanine (G) and cytosine (C). If the genome were a book, each chromosome would be a chapter, each gene on a particular chromosome would be a paragraph and each paragraph would be made of individual letters (A, T, G or C). </p>
<p>One can imagine a book with over 3 billion characters might need editing to correct mistakes that occurred during the writing or copying processes. </p>
<p>Genome editing is a way for scientists to make specific changes to the DNA in a cell or in an entire organism by adding, removing or swapping in or out one or more nucleotides. In people, these changes can be done in somatic cells, those with DNA that cannot be inherited by offspring, or in gamete cells, those containing DNA that can be passed on to offspring. Genome editing of gamete cells, which includes egg or sperm, is controversial, as any changes would be passed on to descendants. Most <a href="https://doi.org/10.1089/crispr.2020.0082">existing guidelines and policies</a> prohibit its use at this time.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/TdBAHexVYzc?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Geneticist Jennifer Doudna is one of the co-inventors of CRISPR/Cas9.</span></figcaption>
</figure>
<h2>How CRISPR works</h2>
<p>In 2012, scientists published a <a href="https://doi.org/10.1126/science.1225829">groundbreaking study</a> demonstrating how CRISPR, or Clustered Regularly Interspaced Short Palindromic Repeats, can be used to accurately change specific DNA sequences.</p>
<p>CRISPR’s natural origins are as a kind of immune response for bacteria. Bacteria that can be infected with viruses have evolved mechanisms to combat them. When a bacterium is infected with a particular virus, it keeps a small piece of the viral DNA sequence called a “spacer” in its own genome. This spacer is an exact match to the viral DNA. Upon subsequent infection, the bacterium is able to use the spacer to recruit a scissorlike protein called Cas9 that can sever new viral DNA attempting to integrate into the bacterium’s genome. This cut to the genetic material prevents the virus from replicating and killing its bacterial host.</p>
<p>After this discovery, scientists were able to fine-tune the system in the lab to be highly precise. They can sever DNA from a variety of cells, including human cells, at a specific location in the genome and subsequently edit it by adding, removing or swapping nucleotides. This is similar to adding or removing letters and words from a book. </p>
<p>This technology has the potential to treat diseases that have genetic origins. One of the summit’s sessions covered CRISPR’s ongoing experimental use to treat patients with <a href="https://doi.org/10.1056/NEJMoa2031054">sickle cell anemia and beta-thalassemia</a>, two blood disorders caused by mutations in the genes. Notably, genetic modification to treat sickle cell anemia and beta-thalassemia involves editing somatic cells, not germline cells. But as the summit speakers noted, whether these likely expensive therapies will be <a href="https://www.statnews.com/2023/03/07/crispr-sickle-cell-access/">accessible to the people who need them most</a>, especially in low- and middle-income countries, is a problem that requires changes to how treatments are sold.</p>
<figure>
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<figcaption><span class="caption">Scientists have been testing ways to use CRISPR/Cas9 to treat sickle cell anemia.</span></figcaption>
</figure>
<h2>Ethics of human genome editing</h2>
<p><a href="https://doi.org/10.1016%2Fj.jmb.2018.05.044">Many questions remain</a> concerning the safety of genome editing, along with its potential to promote eugenics and exacerbate inequities and inequality.</p>
<p>A number of the summit’s sessions involved discussion on the ethics and regulation of the use of this tool. While the landmark 1979 <a href="https://www.hhs.gov/ohrp/regulations-and-policy/belmont-report/read-the-belmont-report/index.html">Belmont Report</a> outlined several ethical pillars to guide human research in the U.S., it was published before human genome editing was developed. In 2021, the World Health Organization <a href="https://www.who.int/news/item/12-07-2021-who-issues-new-recommendations-on-human-genome-editing-for-the-advancement-of-public-health">issued recommendations on human genome editing</a> as a tool to advance public health. There is <a href="https://doi.org/10.1146/annurev-genom-111320-091930">no current international law</a> governing human genome editing. </p>
<p>There is <a href="https://www.pewresearch.org/internet/2022/03/17/americans-are-closely-divided-over-editing-a-babys-genes-to-reduce-serious-health-risk/">still a debate</a> regarding how to use this technology. Some people equate genome editing to interfering with the work of God and argue that it shouldn’t be used at all, while others recognize its potential value and weigh that against its potential risks. The latter focuses on the fundamental question of <a href="https://www.scientificamerican.com/article/the-dark-side-of-crispr/">where to draw the line</a> between which applications are considered acceptable and which are not. For example, some people will agree that using genome editing to modify a defective gene that may lead to an infant’s death if untreated is acceptable. But these same people may frown upon the use of genome editing to ensure that an unborn child has specific physical features such as blue eyes or blond hair.</p>
<p>Nor is there consensus about <a href="https://doi.org/10.1001/jama.2022.13468">what diseases</a> are desirable targets. For example, it may be acceptable to modify a gene to prevent an infant’s death but not acceptable to modify one that prevents a disease later in life, such as the gene responsible for <a href="https://www.mayoclinic.org/diseases-conditions/huntingtons-disease/symptoms-causes/syc-20356117">Huntington’s disease</a>.</p>
<p>The potential for positive applications of human genome editing is both numerous and tantalizing. But establishing informed regulatory legislation everyone can agree on is and will continue to be a challenge. Conferences such as the human genome editing summit are one way to continue important discussions and educate the scientific community and the public on the benefits and risks of genome editing.</p><img src="https://counter.theconversation.com/content/200983/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Andre Hudson receives funding from the National Institutes of Health</span></em></p><p class="fine-print"><em><span>Gary Skuse has received funding from the National Science Foundation. </span></em></p>Following the controversial births of the first gene-edited babies, a major focus of the Third International Summit on Human Genome Editing was responsible use of CRISPR.André O. Hudson, Interim Dean/Professor-College of Science, Rochester Institute of TechnologyGary Skuse, Professor of Bioinformatics, Rochester Institute of TechnologyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1972212023-01-05T20:33:11Z2023-01-05T20:33:11ZDNA reveals large migration into Scandinavia during the Viking age<figure><img src="https://images.theconversation.com/files/503216/original/file-20230105-20-c8gnzd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">More people moved into Scandinavia in Viking times than at any other time period analysed in the study.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/old-wooden-viking-snekkja-longship-type-2044280747">Shutterstock</a></span></figcaption></figure><p>We often think of the Vikings as ultimate explorers, taking their culture with them to far-off lands. But we may not typically think of Viking age Scandinavia as a hub for migration from all over Europe.</p>
<p><a href="https://www.cell.com/cell/fulltext/S0092-8674(22)01468-4">In a study published in Cell</a>, we show this is exactly what happened. The Viking period (late 8th century to mid 11th century) was the catalyst for an exceptional inflow of people into Scandinavia. These movements were greater than for any other period we analysed.</p>
<p>What’s also striking is that later Scandinavians don’t show the same high levels of non-local ancestry present in their Viking-era counterparts. We don’t completely understand why the migrants’ genetic impact was reduced in later Scandinavians, but there are some possibilities.</p>
<p>We analysed genomes (the full complement of DNA contained in human cells) from around 17,000 Scandinavian individuals, including nearly 300 from ancient burials. We combined <a href="https://www.sciencedirect.com/science/article/pii/S0960982218308443">existing datasets</a> with new samples. These were analysed together in a dataset spanning 2,000 years.</p>
<p>We used these genomes to explore when people arrived in the region from outside and where they came from. New DNA samples were collected from several iconic Swedish archaeological sites. </p>
<p>These included Sandby borg, which is a “ring fortress” <a href="https://www.cambridge.org/core/journals/antiquity/article/moment-frozen-in-time-evidence-of-a-late-fifthcentury-massacre-at-sandby-borg/5C803B7E77A41439BC3B50D4BF96560E">where a massacre occurred just before 500 AD</a>, and the Vendel cemetery, which features several burials contained in large boats and dating to between the 6th and 8th centuries AD. We also used samples from Viking chamber burials and remains from Kronan, a <a href="https://www.tandfonline.com/doi/abs/10.1111/j.1095-9270.1990.tb00276.x">warship that capsized with more than 800 men</a> in 1676.</p>
<p>Two previous studies <a href="https://www.sciencedirect.com/science/article/pii/S0960982218308443">noted extensive migration</a> into Scandinavia <a href="https://www.nature.com/articles/s41586-020-2688-8">during the Viking age</a>. But in our latest study, we have clarified some of the details about this flow of genes into the region.</p>
<p>We found that movements of people from western Europe impacted all of Scandinavia, while migration from the east was more localised, with peaks in the Lake Mälaren Valley and Gotland. Finally, gene flow from southern Europe largely affected the south of Scandinavia. </p>
<p>Since the study was based on a 2,000-year chronology, it was not only possible to see there was an increase in migration during the Viking era, but also that it starts to fall with the onset of the medieval period.</p>
<p>The non-local ancestry that arrives in the region at this time falls away in later periods. Much of the genetic influence from eastern Europe disappears and the western and southern influence becomes significantly diluted. The best way to explain this is that people who arrived in Scandinavia during Viking times did not have as many children as the people who were already living there.</p>
<p>There are different possible reasons for this. The migrants could have belonged to groups that did not intend to settle down in Scandinavia, instead aiming to return to where they came from. Tradespeople and diplomats are examples in this category. Additionally, the migrants could also have belonged to groups that were not allowed to have families or children, such as slaves and priests.</p>
<p>We also looked at influences that began at earlier periods in time. For example, the DNA of modern Scandinavians <a href="https://www.nature.com/articles/s41431-021-00899-6">changes gradually as you travel from north to south</a>. This genetic “cline”, or gradient, is due to migrations into the region of people carrying shared genetic similarities known as the Uralic component.</p>
<p>Modern examples of where the Uralic genetic component can be found are among Sami people, people in modern Finland, some Native Americans and some central Asian groups. </p>
<p>In our dataset, we found occasional instances of people with Uralic ancestry – mainly in northern Scandinavia – during the Viking period and medieval times. But the Uralic influence seems to increase after this time, since individuals from our 17th century sample have similar levels of this ancestry to people living today.</p>
<p>There were many other fascinating stories from our study. For example, at the Viking age burial site of Sala, by the river Sagån, we find a woman that seems to be fully British or Irish in her genomic composition. This woman was buried in a prestigious Viking period boat burial. We don’t know exactly what position she held in society, but she would not have been a slave or a priest. </p>
<p>Among the individuals found on the wreck of the Kronan, there were two people who came from what is now Finland and another who has a genetic affinity with people from the Baltic states, such as Lithuania and Latvia (though this identification is not conclusive). At the time of the Kronan incident in 1676, these areas were part of the Swedish Empire, though they are independent today.</p>
<p>The work sheds more light on the historical events that shaped the populations of Scandinavia over time. The Viking age was marked by Scandinavians’ curiosity of the world outside their home region. But, from our results, it also appears that the world outside this region was curious enough about the Vikings to travel to Scandinavia.</p><img src="https://counter.theconversation.com/content/197221/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Anders Götherström receives funding from VR, KVA, and EU. </span></em></p><p class="fine-print"><em><span>Ricardo Rodriguez Varela 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>DNA analysis reveals a large migration of people into Scandinavia during Viking times.Anders Götherström, Professor in Molecular Archaeology, Department of Archaeology and Classical Studies, Stockholm UniversityRicardo Rodriguez Varela, Research in Molecular Archaeology, Department of Archaeology and Classical Studies, Stockholm University, Stockholm UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1961132022-12-08T19:24:21Z2022-12-08T19:24:21ZDNA from elusive human relatives the Denisovans has left a curious mark on modern people in New Guinea<figure><img src="https://images.theconversation.com/files/499706/original/file-20221208-16-p3m533.jpg?ixlib=rb-1.1.0&rect=301%2C139%2C3309%2C2283&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Derek R. Audette/Shutterstock</span></span></figcaption></figure><p>An encounter with a mysterious and extinct human relative – the Denisovans – has left a mark on the immune traits of modern Papuans, in particular those living on New Guinea Island.</p>
<p>This is a new discovery we describe <a href="https://doi.org/10.1371/journal.pgen.1010470">in a study published in PLoS Genetics</a> today. It further suggests that our modern human diversity didn’t just evolve – some parts of it we got from other, extinct human groups.</p>
<h2>DNA from our evolutionary cousins</h2>
<p>Humans are the only living species of the <em>Homo</em> genus. But until 50,000 years ago, our ancestors coexisted – and sometimes interacted – with multiple other <em>Homo</em> groups across the globe. Most of them we know only by <a href="https://onlinelibrary.wiley.com/doi/abs/10.1002/jqs.3137">sparse archaeological remains</a>, which offer tantalising glimpses of our evolutionary cousins.</p>
<p>But for two groups there is something else: DNA. Thanks to technological advances, scientists have retrieved DNA from fossils and sequenced it. As a result, we now have complete genome sequences of the best-known archaic hominins, the <a href="http://www.sciencemag.org/cgi/doi/10.1126/science.1188021">Neanderthals</a>, and a far more elusive group, <a href="http://www.nature.com/articles/nature09710">Denisovans</a>.</p>
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<strong>
Read more:
<a href="https://theconversation.com/fresh-clues-to-the-life-and-times-of-the-denisovans-a-little-known-ancient-group-of-humans-110504">Fresh clues to the life and times of the Denisovans, a little-known ancient group of humans</a>
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<p>Although many Neanderthal fossils have been unearthed all over Europe since they were first identified in the 1860s, the number of known Denisovan fossils fits in the palm of a hand – literally! </p>
<p>The genome sequence we have comes from the smallest bone of a pinky finger. It belonged to the 60,000-year-old remains of a teenage girl from a cave in Siberia, the largest known Denisovan fossil until recently. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/499709/original/file-20221208-16-4pofku.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="The outline of a skeleton finger on a dark surface with a small, orange bone sitting atop one knuckle" src="https://images.theconversation.com/files/499709/original/file-20221208-16-4pofku.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/499709/original/file-20221208-16-4pofku.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/499709/original/file-20221208-16-4pofku.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/499709/original/file-20221208-16-4pofku.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/499709/original/file-20221208-16-4pofku.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/499709/original/file-20221208-16-4pofku.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/499709/original/file-20221208-16-4pofku.jpeg?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">A museum replica of the Denisovan finger bone used to extract ancient DNA.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Denisova_Phalanx_distalis.jpg">Thilo Parg/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<h2>Traces of ancestors</h2>
<p>These genome sequences have transformed the way we think about our extinct relatives. For one, they quickly demonstrated that as humans expanded outside Africa, we had sex – and children – with these other populations.</p>
<p>Traces of their genomes linger in individuals alive today, transmitted across hundreds of generations.</p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/evolutionary-study-suggests-prehistoric-human-fossils-hiding-in-plain-sight-in-southeast-asia-157587">Evolutionary study suggests prehistoric human fossils 'hiding in plain sight' in Southeast Asia</a>
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<p>In the case of Neanderthals, these traces are in all individuals of non-African ancestry today. In the case of Denisovans, we find small traces of their genome in people from all over Asia – especially in Papua New Guinea, and in the island nations of Southeast Asia, where individuals may owe up to 4–5% of their genome to these ancestors. </p>
<p>But identifying these fragments of DNA in our genomes is only the beginning. </p>
<h2>The DNA makes a difference</h2>
<p>The real challenge is to find the biological consequences of this DNA for the people who carry it – which, it bears remembering, is the vast majority of humans. Our specific research question was to pinpoint the molecular processes that might be affected by its presence.</p>
<p>Studies of Neanderthal DNA have shown that genetic variants inherited from them <a href="https://doi.org/10.1093/molbev/msab304">can alter the levels</a> at which some human genes are expressed, for example. We also know Neanderthals have contributed to <a href="https://linkinghub.elsevier.com/retrieve/pii/S0002929715004863">our immune systems</a> (including differences in how people respond to infection with COVID-19), and to <a href="https://www.nature.com/articles/s41467-021-24582-y">variation in skin and hair colour</a>. </p>
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<strong>
Read more:
<a href="https://theconversation.com/what-teeth-can-tell-about-the-lives-and-environments-of-ancient-humans-and-neanderthals-104923">What teeth can tell about the lives and environments of ancient humans and Neanderthals</a>
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<p>But it has never been clear whether Denisovan DNA has left similar trends in modern humans. </p>
<p>In 2019, <a href="https://www.cell.com/cell/abstract/S0092-8674(19)30218-1">a study revealed</a> the genomic coordinates where Denisovan DNA might be found within the genome of Papuan individuals – that is, the indigenous people of New Guinea Island – alive today.</p>
<p>This led us to begin looking into these regions, to understand the cellular and biological processes that might be affected by Denisovan DNA. We took a hybrid approach to this question, making computational predictions first, and following up with laboratory-based experiments to validate our findings.</p>
<p>In addition, we took advantage of the known Neanderthal DNA within these people to highlight any Denisovan-specific contribution. This gave us a more integrated understanding of how encounters with these relatives left potential biological and evolutionary consequences in modern humans.</p>
<h2>A unique Denisovan contribution</h2>
<p>We noticed that in Papuans, Denisovan and Neanderthal genetic variants both occasionally occur within parts of the genome responsible for modulating the expression levels of nearby genes.</p>
<p>However, only Denisovan variants are consistently predicted to occur and affect elements controlling the expression levels of immune-related genes.</p>
<p>So, these different sources of DNA might contribute to the genetic and phenotypic diversity within Papuans in different ways.</p>
<p>To validate our predictions, we designed an experiment comparing five Denisovan sequences against their modern human counterpart, and tested their ability to actually affect gene expression levels inside a particular kind of immune cell known as a lymphocyte.</p>
<p>In two of the five cases, the Denisovan variants did have a measurably different impact on the gene expression levels than their modern human counterpart. And they impact genes known to be important players in the response to infectious microbes, including viruses. </p>
<p>The fact that Denisovans, but not Neanderthals, seem to have contributed to the immune systems of present-day Papuans, tells us something about these ancient people, too.</p>
<p>Although little is known about how widely through Asia Denisovans lived, it suggests their immune system changed to adapt to the infectious diseases of their environment.</p>
<p>When humans moved in <a href="https://science.sciencemag.org/content/361/6397/88">60,000 years ago</a>, these bits of DNA likely contributed to our success in settling this part of the world.</p>
<p>While our study is the first to elucidate the contribution of Denisovan DNA within modern human genetic diversity, there are still exciting questions to address. In particular, it is not clear whether the overall contributions of Denisovan and Neanderthal genetic variants consistently differ from each other.</p>
<p>It is also important to note we tested genetic variants in immune cells under resting conditions. This means the same or other genetic variants might have different effects out in the environment – this will be an important question for studies in the future.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/first-ever-genetic-analysis-of-a-neanderthal-family-paints-a-fascinating-picture-of-a-close-knit-community-192595">First-ever genetic analysis of a Neanderthal family paints a fascinating picture of a close-knit community</a>
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<img src="https://counter.theconversation.com/content/196113/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Irene Gallego Romero receives funding from the Australian Research Council, the Leakey Foundation, the Chan-Zuckerberg Initiative, the Royal Society of New Zealand and the French National Research Agency</span></em></p><p class="fine-print"><em><span>Davide Vespasiani 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>Humanity carries traces of other populations in our DNA – and a new study shows how one of these ancestors has influenced the immune systems of modern Papuans.Irene Gallego Romero, Senior Lecturer in Human Genetics, The University of MelbourneDavide Vespasiani, Post-doctoral researcher, The University of MelbourneLicensed 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>
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<figcaption><span class="caption">GWAS studies seek to find genetic associations between individual traits.</span></figcaption>
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<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>
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<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>
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<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>
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<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>
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<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/1844822022-07-06T13:35:37Z2022-07-06T13:35:37ZAfricans make up a tiny portion of genomics data: why there’s an urgent need for change<figure><img src="https://images.theconversation.com/files/471412/original/file-20220628-22-v51h6c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Nigeria provides an excellent lens to look at the genetic diversity of African people.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/sample-being-pipetted-into-a-eppendorf-tube-for-royalty-free-image/1140201417?adppopup=true">Getty Images </a></span></figcaption></figure><p><em>A group of Nigerian scientists, in conjunction with the London School of Hygiene and Tropical Medicine, <a href="https://www.nature.com/articles/s41588-022-01071-6">established</a> the Noncommunicable Diseases Genetic Heritage Study consortium in February 2020. The aim is to produce a comprehensive catalogue of human genetic variation in Nigeria and assess the burden of noncommunicable diseases in 100,000 adults in the country. The Conversation Africa asked genetic epidemiologist <a href="https://www.lshtm.ac.uk/aboutus/people/fatumo.segun">Segun Fatumo</a>, one of the leaders of the consortium, to explain what they are doing and why.</em> </p>
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<h2>How does Africa feature in global genomics?</h2>
<p>Until recently, only about <a href="https://www.nature.com/articles/538161a">3% of genomic data</a> being used for genome-wide association studies came from people of African descent. Unfortunately, this proportion has fallen even further, <a href="https://www.nature.com/articles/s41591-021-01672-4">to 1.1% in 2021</a>. This means people of African descent may miss out on the potential benefits of genomic research, including early detection of disease and rational drug design. </p>
<p>The current lack of genomic diversity has led to major scientific opportunities being missed. <a href="https://www.nature.com/articles/ng1509">One study</a> which included people of African descent discovered a gene called <em>PCSK9</em> which helps in lowering bad cholesterol. This study led to new drugs that help prevent heart disease. This benefits everyone irrespective of their ancestry populations. It wouldn’t have been possible without including people of African descent. </p>
<p>Africans have the most diverse genomes of all the human populations because modern <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2953791/">humans originated in Africa</a> and then spread across the globe over the past 80,000 years. Therefore, studying the genome of Africans could uncover genetic variants not found in other populations. Such genes could yield new ways to diagnose, prevent and treat diseases for everyone. </p>
<h2>What does the consortium plan to do?</h2>
<p>We teamed up with <a href="https://54gene.com/">54gene</a>, a health technology platform company that’s building diverse datasets to unlock scientific discoveries. Together we established the <a href="https://www.nature.com/articles/s41588-022-01071-6">NonCommunicable Diseases Genetic Heritage Study consortium</a>. One aim is to develop a catalogue of human genetic variation in 100,000 adults in Nigeria. This will be the largest genomic data resource ever to come from continental Africa. It will be of great value to genomics researchers globally and may help in the prevention and control of noncommunicable diseases in sub-Saharan Africa.</p>
<p>The other aim is to assess Nigeria’s burden of disease. We’re looking at things like haematological cancers and cardiovascular, neurodegenerative, metabolic, kidney function and sickle cell disorders.</p>
<p>Our consortium could serve as a template for large-scale genomics across the continent. We hope it will advance precision medicine and offer insights that will improve the health and well-being of African and global populations. </p>
<p>The consortium has five points on its agenda:</p>
<ul>
<li><p>address health issues of concern for Africans and other populations</p></li>
<li><p>ensure projects meet the highest ethical, legal and socially appropriate standards for research</p></li>
<li><p>generate, process, store and use large genomic datasets</p></li>
<li><p>build research capacity</p></li>
<li><p>develop leaders for genomics in Africa.</p></li>
</ul>
<p>The first step is to collect samples. A minimum of 100,000 research participants have been recruited and samples of biological material like blood and urine have been stored for further genomic studies. </p>
<p>Next is to design a small chip that is able to capture a picture of somebody’s DNA sequence. There are three billion base pairs in any human genome. The chip will capture at least one million genetic variants that are important for different diseases. We are also developing other studies using the whole-genome DNA sequence of all three billion base pairs.</p>
<p>We will also be fostering a scientific community that will empower African genomics scientists to be leaders in the genomic world. We want more people in Africa to be in a position to write the continent’s own genomics agenda.</p>
<h2>Why focus on Nigeria?</h2>
<p>First, Nigeria has one of the most diverse ethnolinguistic concentrations in the world, with more than <a href="http://rogerblench.info/Language/Africa/Nigeria/Atlas%20of%20Nigerian%20Languages%202020.pdf">300 ethnic groups and 500 languages</a>. This diversity is taken as a proxy for potential genetic diversity, as seen in other populations. Data from the Nigerian population provides an excellent lens to look at the genetic diversity of African people. This will ensure that most genetic variations are captured.</p>
<p>Second, with <a href="https://www.statista.com/statistics/1122838/population-of-nigeria/#:%7E:text=As%20of%202022%2C%20Nigeria's%20population%20was%20estimated%20at%20around%20216.7%20million.">over 200 million people</a>, Nigeria represents a quarter of the African population. We are recruiting people from across the six geopolitical zones in Nigeria.</p>
<p>With 100,000 research participants, we will be able to estimate the prevalence of noncommunicable diseases in the population, and understand the associated risk factors. </p>
<p>We are poised to provide information that could be used to develop tools for the <a href="https://pubmed.ncbi.nlm.nih.gov/31537347/">early detection of diseases</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/31537368/">disease prevention strategies</a> and <a href="https://www.healthaffairs.org/doi/10.1377/hlthaff.2017.1595">treatment options</a>. </p>
<h2>What other initiatives are there on the continent?</h2>
<p>Our effort will complement other initiatives like <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138491/">H3Africa</a>, <a href="https://www.sciencedirect.com/science/article/pii/S0092867419311201">Uganda Genome Resource</a> and a few others.</p>
<p>H3Africa was launched in 2012. It has recruited close to 100,000 research participants for genomic research in the last decade and trained over 1,000 African scientists, including me. </p>
<p>The <a href="https://acegid.org/">African Centre of Excellence for Genomics of Infectious Diseases</a> is another successful Nigerian-based initiative. It is making an impact through training, discovery and surveillance of infectious pathogens.</p>
<p>The <a href="http://www.nbgnetwork.org/">Nigerian Bioinformatics and Genomics Network</a> is another. It is fostering genetic research collaboration and provides opportunities for career development in genomics and bioinformatics.</p>
<p>The Uganda Genome Resource is currently <a href="https://theconversation.com/what-weve-learnt-from-building-africas-biggest-genome-library-126293">one of the largest</a> and most successful genomic initiatives in Africa. In 2019, a rich, diverse resource was <a href="https://www.sciencedirect.com/science/article/pii/S0092867419311201">published</a> using data from 6,400 Ugandans. It includes whole genome sequencing of nearly 2,000 people.</p>
<p><em>Aminu Yakubu and Babatunde Olusola helped research this article.</em></p><img src="https://counter.theconversation.com/content/184482/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Segun Fatumo received consultancy fees from 54gene Nigeria Ltd.</span></em></p>A new study hopes to produce a catalogue of human genetic variation and assess the burden of noncommunicable diseases in 100,000 adults in Nigeria.Segun Fatumo, Associate Professor of Genetic epidemiology & Bioinformatics, London School of Hygiene & Tropical MedicineLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1843692022-06-09T12:41:46Z2022-06-09T12:41:46Z‘Jurassic World’ scientists still haven’t learned that just because you can doesn’t mean you should – real-world genetic engineers can learn from the cautionary tale<figure><img src="https://images.theconversation.com/files/467795/original/file-20220608-13-magyim.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2000%2C1500&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">While resurrecting dinosaurs may not be on the docket just yet, gene drives have the power to alter entire species. </span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/dinosaur-in-the-lab-image-what-something-new-life-royalty-free-image/1080567850">Hiroshi Watanabe/DigitalVision via Getty Images</a></span></figcaption></figure><p>“<a href="https://www.jurassicworld.com">Jurassic World: Dominion</a>” is hyperbolic Hollywood entertainment at its best, with an action-packed storyline that refuses to let reality get in the way of a good story. Yet just like its predecessors, it offers an underlying cautionary tale of technological hubris that’s very real.</p>
<p>As I discuss in my book “<a href="https://filmsfromthefuture.com/">Films from the Future</a>,”
Stephen Spielberg’s 1993 “Jurassic Park,” based on Michael Crichton’s 1990 novel, didn’t shy away from grappling with the dangers of unfettered entrepreneurship and irresponsible innovation. Scientists at the time were getting closer to being able to manipulate DNA in the real world, and both book and movie captured emerging concerns that playing God with nature’s genetic code could lead to devastating consequences. This was famously captured by one of the movie’s protagonists, Dr. Ian Malcolm, played by Jeff Goldblum, as he declared, “Your scientists were so preoccupied with whether they could, they didn’t stop to think if they should.”</p>
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<iframe id="noa-web-audio-player" style="border: none" src="https://embed-player.newsoveraudio.com/v4?key=x84olp&id=https://theconversation.com/jurassic-world-scientists-still-havent-learned-that-just-because-you-can-doesnt-mean-you-should-real-world-genetic-engineers-can-learn-from-the-cautionary-tale-184369&bgColor=F5F5F5&color=D8352A&playColor=D8352A" width="100%" height="110px"></iframe>
<p><em>You can listen to more articles from The Conversation, narrated by Noa, <a href="https://theconversation.com/us/topics/audio-narrated-99682">here</a>.</em></p>
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<p>In the latest iteration of the “Jurassic Park” franchise, society is coming to terms with the consequences of innovations that were, at best, ill-conceived. A litany of “coulds” over “shoulds” has led to a future in which resurrected and redesigned dinosaurs roam free, and humanity’s dominance as a species is under threat. </p>
<p>At the heart of these films are questions that are more relevant than ever: Have researchers learned the lesson of “Jurassic Park” and sufficiently closed the gap between “could” and “should”? Or will the science and technology of DNA manipulation continue to outpace any consensus on how to use them ethically and responsibly?</p>
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<figcaption><span class="caption">Imagine a world where dinosaurs and humans coexist.</span></figcaption>
</figure>
<h2>(Re)designing the genome</h2>
<p>The first draft of the human genome <a href="https://doi.org/10.1038/35057062">was published to great fanfare</a> in 2001, setting the stage for scientists to read, redesign and even rewrite complex genetic sequences. </p>
<p>However, existing technologies were time-consuming and expensive, placing genetic manipulation out of reach for many researchers. The first draft of the human genome cost an estimated <a href="https://www.genome.gov/about-genomics/fact-sheets/DNA-Sequencing-Costs-Data">US$300 million</a>, and subsequent whole-genome sequences just under $100 million – a prohibitive amount for all but the most well-funded research groups. As existing technologies were refined and new ones came online, however, smaller labs – and even <a href="https://igem.org/">students</a> and <a href="https://www.wired.com/2014/11/diybio-comes-of-age/">“DIY bio” hobbyists</a> – could experiment more freely with reading and writing genetic code.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/467797/original/file-20220608-22-ddjvfi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A DIY bio lab with equipment arranged on counters and cabinets against the walls." src="https://images.theconversation.com/files/467797/original/file-20220608-22-ddjvfi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/467797/original/file-20220608-22-ddjvfi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=449&fit=crop&dpr=1 600w, https://images.theconversation.com/files/467797/original/file-20220608-22-ddjvfi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=449&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/467797/original/file-20220608-22-ddjvfi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=449&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/467797/original/file-20220608-22-ddjvfi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=564&fit=crop&dpr=1 754w, https://images.theconversation.com/files/467797/original/file-20220608-22-ddjvfi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=564&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/467797/original/file-20220608-22-ddjvfi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=564&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">You can manipulate DNA in the comfort of your own home-based DIY bio lab.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/macowell/4821488307/in/pool-diylabs/">Mackenzie Cowell/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>In 2005, bioengineer Drew Endy proposed that it should be possible to work with DNA the <a href="https://doi.org/10.1038/nature04342">same way that engineers work with electronic components</a>. Much as electronics designers are less concerned with the physics of semiconductors than they are with the components that rely on them, Endy argued that it should be possible to create standardized DNA-based parts called “<a href="https://biobricks.org/">biobricks</a>” that scientists could use without needing to be experts in their underlying biology.</p>
<p>Endy’s and others’ work was foundational to the emerging field of <a href="https://doi.org/10.1038/nrmicro3239">synthetic biology</a>, which applies engineering and design principles to genetic manipulation. </p>
<p>Scientists, engineers and even <a href="https://www.vice.com/en/article/9anmk7/bioart-synthetic-biology-projects">artists</a> began to approach DNA as a biological code that could be digitized, manipulated and redesigned in cyberspace in much the same way as digital photos or videos are. This in turn opened the door to reprogramming plants, microorganisms and fungi to produce <a href="https://doi.org/10.2147/DDDT.S58049">pharmaceutical drugs</a> and other <a href="https://fortune.com/2021/08/06/synthetic-biology-plant-based-meats-bioengineering-environmental-impact/">useful substances</a>. Modified yeast, for example, produces the meaty taste of vegetarian <a href="https://doi.org/10.1038/s41467-020-20122-2">Impossible Burgers</a>.</p>
<p>Despite increasing interest in gene editing, the biggest barrier to the imagination and vision of the early pioneers of synthetic biology was still the speed and cost of editing technologies.</p>
<p>Then CRISPR changed everything.</p>
<h2>The CRISPR revolution</h2>
<p>In 2020, scientists Jennifer Doudna and Emanuelle Charpentier won the <a href="https://doi.org/10.1038/d41586-020-02765-9">Nobel Prize in chemistry</a> for their work on a revolutionary new gene-editing technology that allows researchers to precisely snip out and replace DNA sequences within genes: CRISPR.</p>
<p>CRISPR was quick, cheap and relatively easy to use. And it unleashed the imagination of DNA coders.</p>
<p>More than any previous advance in genetic engineering, CRISPR enabled techniques from digital coding and systems engineering to be applied to biology. This cross-fertilization of ideas and methods led to breakthroughs ranging from using <a href="https://www.smithsonianmag.com/smart-news/scientists-write-hello-world-bacterial-dna-electricity-and-crispr-180976763/">DNA to store computer data</a> to creating 3D “<a href="https://www.advancedsciencenews.com/crispr-cleans-up-dna-origami/">DNA origami” structures</a>.</p>
<p>CRISPR also opened the way for scientists to explore redesigning entire species – including <a href="https://www.npr.org/sections/pictureshow/2013/03/15/174322143/its-called-de-extinction-its-like-jurassic-park-except-its-real">bringing back animals from extinction</a>.</p>
<p><a href="https://doi.org/10.1038/d41586-019-02087-5">Gene drives</a> use CRISPR to directly insert a piece of genetic code into an organism’s genome and ensure that specific traits are inherited by all subsequent generations. Scientists are currently experimenting with this technology to <a href="https://doi.org/10.1038/d41586-021-01186-6">control disease-carrying mosquitoes</a>. </p>
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<figcaption><span class="caption">Gene drives have the potential to alter the genetic makeup of an entire species.</span></figcaption>
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<p>Despite the potential benefits of the technology, gene drives raise serious ethical questions. Even when applied to clear public health threats like mosquitoes, <a href="https://www.nytimes.com/2020/01/08/magazine/gene-drive-mosquitoes.html">these questions are not easy to navigate</a>. They get even more complex when considering hypothetical applications in people, such as <a href="https://slate.com/technology/2019/12/crispr-prime-editing-gene-doping-athletes.html">increasing athletic performance in future generations</a>.</p>
<h2>Gain of function</h2>
<p>Advances in gene editing have also made it easier to genetically alter the behavior of individual cells. This is at the heart of <a href="https://www.weforum.org/agenda/2021/12/how-to-fuel-the-biomanufacturing-revolution/">biomanufacturing technologies</a> that reengineer simple organisms to produce useful substances ranging from <a href="https://simpleflying.com/united-airlines-jet-fuel-from-thin-air/">aviation fuel</a> to <a href="https://www.foodnavigator-usa.com/Article/2022/05/09/Synthetic-biology-and-the-future-of-food.-In-conversation-with-biology-by-design-co-Ginkgo-Bioworks">food additives</a>. </p>
<p>It’s also at the center of controversies surrounding genetically engineered viruses.</p>
<p>Since the beginning of the pandemic, there have been rumors that the virus that causes COVID-19 resulted from genetic experiments gone wrong. While these rumors <a href="https://www.newyorker.com/science/elements/the-mysterious-case-of-the-covid-19-lab-leak-theory">remain unsubstantiated</a>, they’ve renewed debate around the <a href="https://www.nytimes.com/2021/06/20/science/covid-lab-leak-wuhan.html">ethics of gain-of-function research</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/467800/original/file-20220608-20-kw2z6q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Gloved hands holding biohazard sample in lab" src="https://images.theconversation.com/files/467800/original/file-20220608-20-kw2z6q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/467800/original/file-20220608-20-kw2z6q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/467800/original/file-20220608-20-kw2z6q.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/467800/original/file-20220608-20-kw2z6q.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/467800/original/file-20220608-20-kw2z6q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=425&fit=crop&dpr=1 754w, https://images.theconversation.com/files/467800/original/file-20220608-20-kw2z6q.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=425&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/467800/original/file-20220608-20-kw2z6q.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"></a>
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<span class="caption">Modifying the genetic makeup of organisms and pathogens has both risks and benefits.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/arselectronica/36320619976">Ars Electronica/Flickr</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><a href="https://theconversation.com/why-gain-of-function-research-matters-162493">Gain-of-function</a> research uses DNA editing techniques to alter how organisms function, including increasing the ability of viruses to cause disease. Scientists do this to predict and prepare for potential mutations of existing viruses that increase their ability to cause harm. However, such research also raises the possibility of a dangerously enhanced virus’s being released outside the lab, either accidentally or intentionally.</p>
<p>At the same time, scientists’ increasing mastery over biological source code is what has allowed them to <a href="https://www.weforum.org/agenda/2021/07/everything-you-need-to-know-about-mrna-vaccines/">rapidly develop the Pfizer-BioNTech and Moderna mRNA vaccines</a> to combat COVID-19. By precisely engineering the genetic code that instructs cells to produce harmless versions of viral proteins, vaccines are able to prime the immune system to respond when it encounters the actual virus.</p>
<h2>Responsible biological source code manipulation</h2>
<p>Prescient as Michael Crichton was, it’s unlikely that he could have envisioned just how far scientists’ abilities to engineer biology have advanced over the past three decades. <a href="https://www.smithsonianmag.com/science-nature/these-are-extinct-animals-we-can-should-resurrect-180954955/">Bringing back extinct species</a>, while an active area of research, remains <a href="https://doi.org/10.3390%2Fgenes9110548">fiendishly difficult</a>. However, in many ways, our technologies are substantially further along than those in “Jurassic Park” and the subsequent films.</p>
<p>But how have we done on the responsibility front?</p>
<p>Fortunately, consideration of the social and ethical side of gene editing has gone hand in hand with the science’s development. In 1975, scientists <a href="https://doi.org/10.1073/pnas.72.6.198">agreed on approaches</a> to ensure that emerging recombinant DNA research would be carried out safely. From the get-go, the ethical, legal and social dimensions of the science were hard-wired into the <a href="https://www.genome.gov/Funded-Programs-Projects/ELSI-Research-Program-ethical-legal-social-implications">Human Genome Project</a>. DIY bio communities have been at the forefront of <a href="https://doi.org/10.1038/531167a">safe and responsible gene-editing research</a>. And social responsibility is integral to <a href="https://blog.igem.org/blog/2020/9/23/igem-and-the-value-of-responsibility">synthetic biology competitions</a>. </p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/12VfS2hAi7c?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">DNA was never destiny.</span></figcaption>
</figure>
<p>Yet as gene editing becomes increasingly powerful and accessible, a community of well-meaning scientists and engineers is unlikely to be sufficient. While the “Jurassic Park” movies take dramatic license in their portrayal of the future, they do get one thing right: Even with good intentions, bad things happen when you mix powerful technologies with scientists who haven’t been trained to think through the consequences of their actions – and haven’t thought to ask experts who have.</p>
<p>Maybe this is the abiding message of “Jurassic World: Dominion” – that despite incredible advances in genetic design and engineering, things can and will go wrong if we don’t embrace the development and use of the technology in socially responsible ways.</p>
<p>The good news is that we still have time to close the gap between “could” and “should” in how scientists redesign and reengineer genetic code. But as “Jurassic World: Dominion” reminds moviegoers, the future is often closer than it might appear.</p><img src="https://counter.theconversation.com/content/184369/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Andrew Maynard 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>As genetic engineering and DNA manipulation tools like CRISPR continue to advance, the distinction between what science ‘could’ and ‘should’ do becomes murkier.Andrew Maynard, Professor of Responsible Innovation, Arizona State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1811322022-04-19T14:55:13Z2022-04-19T14:55:13Z‘Living with COVID-19’ must be more than an empty phrase: Individuals need tools to manage BA.2 and future waves<figure><img src="https://images.theconversation.com/files/458247/original/file-20220414-24-xhspoa.JPG?ixlib=rb-1.1.0&rect=18%2C119%2C3300%2C2527&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Ontario Chief Medical Officer of Health Kieran Moore arrives to speak at a press conference at Queen’s Park on April 11, 2022. Ontario lifted most COVID-19 restrictions in March.</span> <span class="attribution"><span class="source">THE CANADIAN PRESS/Nathan Denette</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/-living-with-covid-19--must-be-more-than-an-empty-phrase--individuals-need-tools-to-manage-ba-2-and-future-waves" width="100%" height="400"></iframe>
<p>When Ontario lifted public health protective measures in March, the expectation was that we might see a <a href="https://www.ctvnews.ca/mobile/health/coronavirus/bump-in-covid-19-cases-not-unexpected-as-public-health-measures-lifted-tam-says-1.5825004?cache=/5-things-to-know-for-monday-september-30-2019-1.4616452">small but manageable bump in COVID-19 cases</a>. At the same time, Canadians were being told that it was time to learn to “<a href="https://www.cbc.ca/news/canada/toronto/ontario-covid19-march-8-2022-1.6376793">live with COVID</a>.” </p>
<p>The decision to lift the public health protective measures happened while many countries in Africa, <a href="https://www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-19---15-february-2022">Europe and South Asia</a> were going through another Omicron-like surge, caused by one of its subvariants, BA.2. Many of these countries also removed their public health protective measures. In <a href="https://arstechnica.com/science/2022/04/cdc-study-spotlights-utter-failure-of-chinas-covid-zero-policy-in-hong-kong/">Hong Kong</a>, while the restrictions were being removed, BA.2 hit like a tsunami with massive casualties among people age 60 years and over. <a href="https://www.cdc.gov/mmwr/volumes/71/wr/mm7115e1.htm?s_cid=mm7115e1_w">China</a> was also dealing with an Omicron BA.2 surge. </p>
<p>In Ontario, authorities had hoped the BA.2 wave would somehow pass by. However, instead of the <a href="https://beta.ctvnews.ca/local/toronto/2022/4/5/1_5849600.amp.html">expected small bump in cases</a>, current predictions are at <a href="https://toronto.ctvnews.ca/ontario-likely-seeing-100k-to-120k-new-covid-19-cases-each-day-head-of-science-table-says-1.5851187">100,000 cases per day</a>, which is likely an underestimation due to lack of wider testing. <a href="https://www.cbc.ca/news/canada/toronto/ontario-daily-covid-file-april-5-2022-1.6408672">COVID-19 hospitalizations have surpassed 1,000 in Ontario</a>. </p>
<p>Although Ontario is now better prepared to handle higher cases of <a href="https://news.ontario.ca/en/release/1001411/ontario-continues-to-add-hospital-beds-and-build-up-health-workforce">hospitalization and intensive care admissions</a>, its challenge may now be to handle large absenteeism in health care and other sectors. The recent chaos in <a href="https://www.thetimes.co.uk/article/covid-chaos-at-uk-airports-spreads-to-border-officials-b0h0x5vqm">British airports</a> and at other borders illustrates the potential impact of BA.2.</p>
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Read more:
<a href="https://theconversation.com/why-its-normal-for-covid-19-vaccine-immunity-to-wane-and-how-booster-shots-can-help-171786">Why it's normal for COVID-19 vaccine immunity to wane, and how booster shots can help</a>
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<p>The surge of BA.2 cases in Ontario is related not only to the subvariant’s characteristics, but also to the <a href="https://www.scientificamerican.com/article/vaccines-remain-effective-against-ba-2-but-protection-from-infection-wanes-over-time/">waning of vaccine-induced immune protection</a> against the infection (including in those that had a booster late last year) and, above all, the removal of public health protective measures, such as the mask requirement. </p>
<h2>What do we know about the BA.2 subvariant?</h2>
<figure class="align-right ">
<img alt="A watercolour illustration of a light blue coronavirus with red spikes" src="https://images.theconversation.com/files/458266/original/file-20220414-9085-huglhv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/458266/original/file-20220414-9085-huglhv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/458266/original/file-20220414-9085-huglhv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/458266/original/file-20220414-9085-huglhv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/458266/original/file-20220414-9085-huglhv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/458266/original/file-20220414-9085-huglhv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/458266/original/file-20220414-9085-huglhv.jpg?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">
<figcaption>
<span class="caption">Omicron BA.2 is now the dominant variant worldwide.</span>
<span class="attribution"><span class="source">(Pixabay)</span></span>
</figcaption>
</figure>
<p>BA.2 is believed to have emerged around the same time as the other Omicron variants. The significance of BA.2 became clear with the release of a <a href="https://en.ssi.dk/-/media/arkiv/subsites/covid19/risikovurderinger/2022/risk-assesment-of-omicron-ba2.pdf?la=en">report from Denmark</a> in late January, indicating that this subvariant is 30 per cent more transmissible than Omicron, but with the same virulence (the potential to cause severe disease). </p>
<p>By early April, the World Health Organization reported that BA.2 was the <a href="https://www.who.int/docs/default-source/coronaviruse/situation-reports/20220405_weekly_epi_update_86.pdf?sfvrsn=3f01a460_4&download=true">dominant variant worldwide</a>. A few more Omicron subvariants have already made their debuts, such as BA.1.1, BA.3 <a href="https://www.who.int/director-general/speeches/detail/who-director-general-s-opening-remarks-at-the-who-press-conference-13-April-2022">BA.5</a> and BA2+. Cases of recombination among Omicron subvariants and Delta, such as <a href="https://www.forbes.com/sites/williamhaseltine/2022/04/06/two-more-members-of-the-omicron-family-to-keep-an-eye-on/?sh=5076c6664fea">Omicron XE</a>,<a href="https://nationalpost.com/news/who-says-it-is-analyzing-two-new-omicron-covid-sub-variants">BA.4</a> <a href="https://theconversation.com/deltacron-what-scientists-know-so-far-about-this-new-hybrid-coronavirus-179442">XD</a> and XF, have emerged. </p>
<p>Omicron XE is getting a lot of attention, as its <a href="https://www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-19---5-april-2022">transmissibility is 10 per cent greater</a> than that of BA.2 (or approximately 50 per cent more transmissible than the original Omicron variant, BA.1). It was first detected on <a href="https://time.com/6165297/xe-variant-what-to-know/">Jan. 19 in the United Kingdom</a>.</p>
<p>Research awaiting peer review indicates that <a href="https://doi.org/10.1101/2022.02.19.22271112">re-infection by BA.2</a> is low. However, in those who are re-infected with BA.2, one in four had a prior BA.1 infection. The emergence of variants such as Omicron XE, which results from <a href="https://www.forbes.com/sites/williamhaseltine/2022/03/10/a-new-process-of-sars-cov-2-variation-uncovered-intragenomic-recombination/?sh=66b151a3c8cd">recombination of the genomes of Omicron BA.1 and BA.2</a> in addition to new mutations, suggests that wide circulation of BA.2 among BA.1 impacted populations can significantly contribute to the evolution of SARS-CoV-2. The BA.4 subvariant is the result of <a href="https://www.forbes.com/sites/williamhaseltine/2022/03/16/an-omicron-omicron-recombinant-ba4/?sh=7f1065a059b0">recombination</a> between Omicron BA.1 and BA.3. </p>
<p>Reports that have not yet been peer-reviewed indicate that BA.2 has a slightly higher (30 per cent) <a href="https://arxiv.org/pdf/2202.05031.pdf">immune evasion capability</a> (ability to bypass immunity from vaccines or previous infections) and higher <a href="https://doi.org/10.1101/2022.03.26.22272984">viral shedding</a> (release of virus particles by an infected person) than Omicron. These factors could explain its higher transmissibility than Omicron, while the severity and symptoms remain similar to <a href="https://www.theguardian.com/world/2022/apr/07/omicron-variant-does-cause-different-symptoms-from-delta-study-finds?CMP=oth_b-aplnews_d-1">Omicron</a>.</p>
<h2>What does it mean to ‘live with COVID-19?’</h2>
<p>Two years into the pandemic, there’s a lot that experts have learned about SARS-CoV-2. However, humans keep enabling its circulation, <a href="https://theconversation.com/how-new-covid-19-variants-emerge-natural-selection-and-the-evolution-of-sars-cov-2-176030">giving the virus the chance to evolve</a>. We are not in a position to predict the future of this pandemic, just yet. </p>
<p>Since the beginning of the pandemic, the public was asked to listen to the advice of experts and public health officials. Now the public is being told to learn to live with COVID-19. At the same time, <a href="https://www.thewhig.com/news/covid-19-testing-remains-limited-as-sixth-wave-hits-ontario">testing has become limited</a> and little to no <a href="https://globalnews.ca/news/8753953/covid-19-canada-6th-wave-risk-assessment-challenges/">information on daily COVID-19 cases</a> is now provided in some parts of Canada. So, any chance for the public to check the COVID “weather,” get a forecast and prepare for it is diminished. We are now living in a COVID fog.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/458268/original/file-20220414-18-zqvagf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Three people in face masks and shields carrying bags and packages." src="https://images.theconversation.com/files/458268/original/file-20220414-18-zqvagf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/458268/original/file-20220414-18-zqvagf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/458268/original/file-20220414-18-zqvagf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/458268/original/file-20220414-18-zqvagf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/458268/original/file-20220414-18-zqvagf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/458268/original/file-20220414-18-zqvagf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/458268/original/file-20220414-18-zqvagf.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">Hong Kong Chief Executive Carrie Lam, left, holds a package of coronavirus prevention materials to be delivered to people during an event on April 2, 2022. Hong Kong authorities asked the entire population to voluntarily test themselves for COVID-19 at home for three days in a row.</span>
<span class="attribution"><span class="source">(AP Photo/Kin Cheung)</span></span>
</figcaption>
</figure>
<p>In the summer of 2020, as Ontario was contemplating lifting lockdowns, public health experts looked for key indicators to sustain such measures. A <a href="https://globalhealth.harvard.edu/evidence-roundup-why-positive-test-rates-need-to-fall-below-3/">three per cent positivity rate</a> was considered to be a sufficiently safe community transmission rate to remove the public health protective measures. We are in a better position now with around <a href="https://covid19tracker.ca/vaccinationtracker.html">86 per cent vaccine coverage</a> among those over five years old, and many people have grown accustomed to face masks, so it’s likely that we can handle a higher positivity rate. The question is, how much higher? </p>
<p>The answer would be a useful indicator for the public to make COVID-19 protection choices. This is not about living with a <a href="https://nationalpost.com/opinion/rupa-subramanya-doug-ford-must-resist-covid-zero-zealots">zero-COVID policy</a>. It is about empowering the public with up-to-date information and providing the right tools to weather a COVID-19 storm. Individuals cannot protect themselves on their own, nor should they have to.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/whats-next-with-face-masks-keep-wearing-them-in-public-wear-the-best-mask-available-and-pay-attention-to-fit-177237">What's next with face masks? Keep wearing them in public, wear the best mask available and pay attention to fit</a>
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<p>We do have vaccines, but their protection against infection wanes with time. In addition, it does not seem like <a href="https://www.reuters.com/article/us-health-coronavirus-israel-study-idCAKCN2LY06B">we can boost our way out</a> of this pandemic. We have the antiviral medications, such as <a href="https://covid-vaccine.canada.ca/info/paxlovid-en.html">Paxlovid</a>, but they need to be administered in the early days of an infection. But without testing, how would one know when to take it? </p>
<p>In addition, <a href="https://www.theglobeandmail.com/canada/article-covid-19-antiviral-drug-paxlovid-being-dispensed-at-low-rates-across/">distribution and administration</a> of this medication has hit a wall in Canada. We have the masks that work very well, but the empty phrase “<a href="https://www.ctvnews.ca/health/coronavirus/get-used-to-it-outbreaks-give-americans-taste-of-living-with-virus-1.5854754">living with the virus</a>” has muddled the significance of this simple, and yet protective, measure.</p>
<p>Instead of minimizing or dismissing this new wave of COVID-19, as well as future waves, we need for strategies to deal with new COVID-19 waves in an efficient way. The U.S. <a href="https://www.popsci.com/health/fda-advisors-meet-future-vaccine-strategy/">Food and Drug Administration</a> recently held a meeting to brainstorm new ways to provide sustainable immune protection in the face of an ever-changing SARS-CoV-2 virus. Canada should follow suit. </p>
<p>Governments should follow the science and provide the means to live with virus: information about the emergence of new variants, number of daily cases, access to testing and solutions for longer-lasting immune protection with different vaccine technologies. Then we can all live a healthy life with COVID-19.</p><img src="https://counter.theconversation.com/content/181132/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Dasantila Golemi-Kotra 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>Instead of minimizing current or future waves of COVID-19, we need strategies to deal with new variants efficiently. Only then can we live with the virus in a healthy way.Dasantila Golemi-Kotra, Professor, Biology, York University, CanadaLicensed 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>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1415692472156495875"}"></div></p>
<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>
<figcaption>
<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>
</figcaption>
</figure>
<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>
<figcaption>
<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>
</figcaption>
</figure>
<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>
<figure>
<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>
</figure>
<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>
<p>[<em>Get fascinating science, health and technology news.</em> <a href="https://memberservices.theconversation.com/newsletters/?nl=science&source=inline-science-fascinating">Sign up for The Conversation’s weekly science newsletter</a>.]</p><img src="https://counter.theconversation.com/content/176138/count.gif" alt="The Conversation" width="1" height="1" />
<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.tag:theconversation.com,2011:article/1789122022-03-15T14:25:12Z2022-03-15T14:25:12ZThe coronavirus in Nigeria has its own family history: keeping track is vital<figure><img src="https://images.theconversation.com/files/451813/original/file-20220314-115412-sn4z19.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Inequality in coronavirus genomic surveillance delays the detection of globally significant variants of concern.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/october-2021-el-salvador-san-jos%C3%A9-dr-carlos-ortega-of-the-news-photo/1236170661?adppopup=true"> Camilo Freedman/ picture alliance via Getty Images</a></span></figcaption></figure><p>Nigeria <a href="https://www.health.gov.ng/index.php?option=com_k2&view=item&id=613:health-minister-first-case-of-covid-19-confirmed-in-nigeria">recorded</a> its first case of SARS-CoV-2 on 27 February 2020, and within five months at least one case had been reported in all states across the country. </p>
<p>By 11 March 2020, SARS-CoV-2 had infected over 100,000 people in at least 100 countries. The World Health Organisation consequently <a href="https://www.who.int/director-general/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020">declared</a> it a pandemic. </p>
<p>Building on the success of Nigeria’s <a href="https://theconversation.com/how-nigeria-beat-the-ebola-virus-in-three-months-41372">response to Ebola</a>, the Nigerian government immediately <a href="https://www.nature.com/articles/d41591-020-00004-2">activated</a> a national Incident Control Centre. This was to enable routine surveillance, diagnosis, and prompt reporting of COVID-19 cases. The <a href="https://ncdc.gov.ng/">Nigeria Centre for Disease Control</a> swiftly identified and accredited 70 <a href="https://covid19.ncdc.gov.ng/laboratory/">laboratories</a> (now 85) in the country. </p>
<p>These were equipped with the skills, infrastructure and materials needed for molecular detection of SARS-CoV-2. Subsequently, real-time epidemiological information for routine surveillance of cases across the country was captured in an open source mobile health <a href="https://innov.afro.who.int/emerging-technological-innovations/sormas-surveillance-outbreak-response-management-and-analysis-system-2084">system</a>. This Surveillance Outbreak Response Management and Analysis System helps to detect outbreaks early and manage them. When a health worker adds a suspected or confirmed case to the system, it automatically triggers a series of actions. </p>
<p>Even before COVID-19, however, Nigeria’s healthcare system was <a href="https://theconversation.com/why-nigerias-weak-health-system-affects-women-and-girls-the-most-163904">relatively weak</a>, with many challenges. With the onset of the pandemic, resources became even more stretched. Testing capacity was limited, and a densely settled population with poor healthcare infrastructure made Nigeria a fertile ground for the spread of SARS-CoV-2. </p>
<p>Nigeria has a <a href="https://www.worldometers.info/world-population/nigeria-population/">population</a> of over 200 million people. <a href="https://tradingeconomics.com/nigeria/population-ages-65-and-above-percent-of-total-wb-data.html">Roughly 2.7%</a> are aged 65 years or older and thus at risk of severe COVID-19. A significant proportion of the population has pre-existing underlying health conditions such as diabetes, high blood pressure, cardiovascular diseases and cancers. These diseases increase their risk for severe COVID-19. An estimated <a href="https://www.reuters.com/article/us-nigeria-economy-poverty/forty-percent-of-nigerians-live-in-poverty-stats-office-idUSKBN22G19A">83 million</a> (40%) of Nigeria’s people live below the poverty line. Consequently, they face steep disadvantages in healthcare. Nigerians also face a high disease burden from other viral pathogens including Lassa fever, yellow fever and measles. </p>
<p>Nigeria is a centre of commerce and travel in Africa. We were <a href="https://www.nature.com/articles/s41467-022-28317-5">concerned</a> that undetected expansion of a more infectious, virulent, or immune-resistant variant of SARS-CoV-2 in the region could have major repercussions. It was also important to know more about the genetic makeup of the virus in Nigeria and whether it was changing. </p>
<p>We collected and analysed hundreds of samples from COVID-19 infected individuals in the southwestern region of the country between July 2020 and August 2021. We found the B.1.1.7 alpha “variant of concern” and the B.1.525 eta lineage were expanding in late 2020. The uncommon delta AY.36 lineage of concern followed, expanding by the summer of 2021. Eta and delta AY.36 were dominant in Nigeria but rare elsewhere. This suggests that distinct viral population dynamics were underlying the epidemic in West Africa. </p>
<p>The findings underline the importance of improving genomic surveillance efforts to better understand and monitor new variants as they arise in different parts of the world. This could prevent threats to vulnerable health systems and populations.</p>
<h2>Variants in Nigeria</h2>
<p>In the first year of the pandemic, Nigeria needed more consistent and higher volume collection of viral samples. Consequently, we set out to identify the circulating variants of SARS-CoV-2 in Nigeria and monitor them over time. We collected samples from the Biorepository and Clinical Virology Laboratory at the College of Medicine, University College Hospital in Ibadan. This laboratory receives samples primarily from Oyo State and other health facilities in the southwestern region of the country. </p>
<p>We extracted ribonucleic acid from the samples and chemically made many copies of the material at the Ibadan laboratory. This process is called quantitative polymerase chain reaction. It enables detection and quantification of the virus in infected individuals. Genomic sequencing and phylogenetic analysis were completed at the Northwestern University, Illinois, Chicago. <a href="https://www.cdc.gov/coronavirus/2019-ncov/variants/genomic-surveillance.html#:%7E:text=How%20does%20genomic%20sequencing%20work,throughout%20the%20COVID%2D19%20pandemic.">Genomic sequencing</a> allows scientists to classify a virus as a particular variant and determine its lineage. </p>
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Read more:
<a href="https://theconversation.com/nigerian-scientists-have-identified-seven-lineages-of-sars-cov-2-why-it-matters-144234">Nigerian scientists have identified seven lineages of SARS-CoV-2: why it matters</a>
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<p>We reported sequences from 378 SARS-CoV-2 isolates collected in Oyo State, Nigeria between July 2020 and August 2021. Before this, Nigeria had a total of only 856 sequences in the <a href="https://www.gisaid.org/">Global Initiative on Sharing Avian Influenza Data</a> database. Our submissions thus increased reporting by nearly 50%. </p>
<p>Our results show that in early 2021, most isolates belonged to the B.1.1.7 alpha “variant of concern” or the B.1.525 eta lineage. Eta later outcompeted alpha in Nigeria and across West Africa, persisting in the region even after the expansion of an otherwise rare delta sub-lineage. Analysis suggests that eta <a href="https://www.nature.com/articles/s41467-022-28317-5">originated</a> in West Africa before spreading globally.</p>
<p>Further analysis suggests that eta could have have been considered a variant of concern in early 2021 had it not been overlooked due to under-sampling in the region. These gaps in surveillance mean there may be new variants popping up around the world, unseen. We should not be caught unprepared by a new variant with unique properties.</p>
<p>Our study confirmed the circulation and expansion of SARS-CoV-2 variants in the population. It also confirmed how a globally uncommon lineage, AY.36, became dominant in the region at some point. It thus emphasises the importance of surveillance and monitoring of SARS-CoV-2 infection to ensure early detection of new variants in Nigeria and the West Africa region.</p>
<h2>Research capacity and collaboration</h2>
<p>Our study confirms speculation that there was previously inadequate surveillance and under-reporting of cases of SARS-CoV-2 in Nigeria and in a number of other countries. </p>
<p>It also demonstrates the research capacities in Nigeria and the strength of research collaborations between institutions.</p><img src="https://counter.theconversation.com/content/178912/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Olubusuyi Moses Adewumi receives funding from local and international bodies for scientific research. </span></em></p>Improving genomic surveillance to better understand new variants as they arise in different parts of the world could prevent threats to vulnerable health systems and populations.Olubusuyi Moses Adewumi, Virologist , University of IbadanLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1754802022-02-03T13:11:18Z2022-02-03T13:11:18ZRecord-breaking rapid DNA sequencing promises timely diagnosis for thousands of rare disease cases<figure><img src="https://images.theconversation.com/files/444145/original/file-20220202-23996-qrz7h1.jpg?ixlib=rb-1.1.0&rect=0%2C7%2C5184%2C3437&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">For patients, often children, with rare diseases, getting a diagnosis is difficult and time-consuming.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/pediatrician-meeting-with-mother-and-child-in-royalty-free-image/629600296">monkeybusinessimages/iStock via Getty Images</a></span></figcaption></figure><p>For children suffering from rare diseases, it usually <a href="https://www.globalrarediseasecommission.com/Report">takes years to receive a diagnosis</a>. This “<a href="https://www.raconteur.net/infographics/the-diagnostic-odyssey/">diagnostic odyssey</a>” is filled with multiple referrals and a barrage of tests, seeking to uncover the root cause behind mysterious and debilitating symptoms. </p>
<p>A new speed record in DNA sequencing may soon help families more quickly find answers to difficult and life-altering questions. </p>
<p>In just <a href="https://doi.org/10.1056/NEJMc2112090">7 hours, 18 minutes</a>, a team of researchers at Stanford Medicine went from collecting a blood sample to offering a disease diagnosis. This unprecedented turnaround time is the result of ultra-rapid DNA sequencing technology paired with massive cloud storage and computing. This improved method of diagnosing diseases allows researchers to discover previously undocumented sources of genetic diseases, shining new light on the <a href="https://www.genome.gov/human-genome-project/Completion-FAQ#:%7E:text=with%20a%20G.-,The%20human%20genome%20contains%20approximately%203%20billion%20of%20these%20base,nucleus%20of%20all%20our%20cells.">6 billion letters</a> in the human genome.</p>
<p>More than <a href="https://www.nichd.nih.gov/newsroom/resources/spotlight/020116-rare-disease-day">7,000 rare diseases</a> affect <a href="https://doi.org/10.1038/s41431-019-0508-0">300 million people worldwide</a>, 50% of whom are children. Of these diseases, <a href="https://doi.org/10.1016/S2213-8587(19)30006-3">80% have a genetic component</a>. The onset of some rare genetic diseases can be swift and debilitating. Spotting symptoms and identifying the root cause is a race against the clock for many families.</p>
<p>I’m a <a href="https://scholar.google.com/citations?user=F5ogte8AAAAJ&hl=en">biotechnology and policy scholar</a> who works on improving access to innovative health care technologies. Whether it’s simple and affordable tests or <a href="https://theconversation.com/new-gene-therapies-may-soon-treat-dozens-of-rare-diseases-but-million-dollar-price-tags-will-put-them-out-of-reach-for-many-164990">sophisticated and expensive gene therapies</a>, medical breakthroughs need to reach populations around the world. I believe that ultra-rapid DNA sequencing is key to casting a wider net and providing a faster turnaround for diagnosing rare diseases.</p>
<h2>A new Guinness World Record</h2>
<p>The <a href="https://www.genome.gov/human-genome-project">Human Genome Project</a>, the first successful attempt to sequence a complete or “whole” human genome, took 13 years, from 1990 to 2003, and cost $2.7 billion. In 2014, the field of whole genome sequencing passed another major milestone by hitting the <a href="https://www.forbes.com/sites/matthewherper/2014/01/14/the-1000-genome-arrives-for-real-this-time/?sh=476fbb015796">$1,000 price point</a>. Every year, the cost of sequencing continues to fall, driven by engineering and computational innovation.</p>
<p>In their quest for a world record, Stanford researchers reached for a DNA sequencing platform from the company <a href="https://nanoporetech.com/">Oxford Nanopore Technologies</a>, which developed a device that reads genomes by <a href="https://www.youtube.com/watch?v=E9-Rm5AoZGw">pulling large strands of DNA through pores</a> comparable in size and composition to the openings in biological cell membranes. As a DNA strand passes through the pore, the device reads subtle electrical changes unique to each DNA letter, thus detecting the DNA sequence.</p>
<p>Thousands of these pores are distributed across a device called a flow cell. The researchers sequenced a single patient’s genome across 48 flow cells simultaneously, allowing them to read the entire genome in a record time of 5 hours, 2 minutes.</p>
<p>The ultra-rapid DNA sequencing generated terabytes of data, which was moved to a <a href="https://blogs.nvidia.com/blog/2022/01/12/world-record-genome-sequencing-parabricks/">cloud-based storage system</a>. In the cloud, algorithms scanned the genome, looking for tiny variations – mutations – within the DNA sequence that could help explain the origin of a genetic disease.</p>
<h2>Rewriting the diagnostic odyssey</h2>
<p>If a disease’s origin is thought to reside in the genome, the standard medical way forward is to order a <a href="https://medlineplus.gov/genetics/understanding/testing/types/">gene panel</a>. This test sequences a list of predetermined genes for possible disease-causing mutations. Receiving test results usually takes <a href="https://www.massgeneral.org/cancer-center/treatments-and-services/cancer-genetics/genetic-testing-frequently-asked-questions">two to three weeks but can take up to eight weeks</a>, and can miss mutations in genes not on the list.</p>
<p>Shortening the sequencing and analysis process to seven hours and expanding the sequencing from a few genes to the entire genome could fundamentally alter the diagnostic odyssey. Ultra-rapid DNA sequencing has already made a difference in the lives of two children.</p>
<p>Matthew Junzman, a 13-year-old from Oregon, was rushed to Stanford Hospital and placed on life support. His heart was failing, and no one knew why. Doctors <a href="https://med.stanford.edu/news/all-news/2022/01/dna-sequencing-technique.html">narrowed down the cause to two options</a>: myocarditis, a reversible condition involving inflammation of the heart, or an untreatable genetic condition.</p>
<p>In the Stanford study, doctors performed an ultra-rapid DNA sequencing test, which quickly revealed that Matthew had a genetic condition. He was immediately placed on a transplant list and received a new heart three weeks later.</p>
<p>In the same study, a 3-month-old patient was <a href="https://med.stanford.edu/news/all-news/2022/01/dna-sequencing-technique.html">admitted to the pediatric hospital suffering from seizures</a>. Using the ultra-rapid DNA sequencing process, doctors quickly spotted a mutation in a gene that explained the seizures. Standard tests would have initially missed this diagnosis.</p>
<h2>Disease diagnosis is a global problem</h2>
<p>Advances in health care technology typically have a high price tag when they first become available. Corporate competition, cheaper materials and new generations of technology can help drive down costs. But infrastructure, political and regulatory hurdles all contribute to limiting global access.</p>
<p>While Oxford Nanopore’s technology is cheaper than several alternative sequencing devices, costs of equipment and materials are still prohibitively expensive for labs in many countries. Similarly, <a href="https://www.worldbank.org/en/publication/wdr2021">less than 20%</a> of low- and middle-income countries have modern data infrastructure. This removes the possibility of cloud computing in many places.</p>
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<figcaption><span class="caption">Researchers in Africa are working to ensure that African populations are represented in and benefit from advances in genomic research.</span></figcaption>
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<p>Bringing ultra-rapid DNA sequencing to these countries will involve investing in regional efforts to support genomic research. For example, the <a href="https://h3africa.org/">Human Heredity & Health in Africa</a> Initiative invests in scientific infrastructure and workforce development to study health and disease for African populations. Providing groups like these with the equipment and software needed for ultra-rapid DNA sequencing will ensure that rare diseases that are more common in African populations will not go unexplored. </p>
<p>There are no approved treatments for <a href="https://doi.org/10.1016/S2213-8587(19)30006-3">95% of rare diseases</a>. The limited number of individuals affected by a given rare disease makes it difficult to study symptoms and design clinical trials. <a href="https://www3.weforum.org/docs/WEF_Global_Data_Access_for_Solving_Rare_Disease_Report_2020.pdf">Creating data-sharing systems and crafting regulations</a> will be vital to allow people to safely share their personal information between countries. The <a href="https://www.ejprarediseases.org/">European Joint Programme on Rare Diseases</a> and the <a href="https://www.ga4gh.org/">Global Alliance for Genomics & Health</a> are making progress toward these goals, building bridges between rare disease communities around the world.</p>
<p>As ultra-rapid genome sequencing becomes a feature in hospitals across high-income countries, I believe it’s important to consider how the broader rare disease community will have access to these tools and benefit from the wave of new disease insight on the horizon.</p>
<p>[<em>Understand new developments in science, health and technology, each week.</em> <a href="https://memberservices.theconversation.com/newsletters/?nl=science&source=inline-science-understand">Subscribe to The Conversation’s science newsletter</a>.]</p><img src="https://counter.theconversation.com/content/175480/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Kevin Doxzen is affiliated with the World Economic Forum. </span></em></p>Record-breaking technology can sequence an entire human genome in a matter of hours. The work could be a lifeline for people suffering from the more than 5,000 known rare genetic diseases.Kevin Doxzen, Postdoctoral Fellow in Precision Medicine and Emerging Biotechnologies, Arizona State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1238142022-02-01T18:47:49Z2022-02-01T18:47:49ZVirtual labs can help students learn, but they can’t replace hands-on experience<p>An ill newborn’s life is hanging by a thread, and only <a href="https://www.nejm.org/doi/full/10.1056/NEJMc2112090?query=featured_home">the right diagnosis</a> will afford her the treatment that may save her life. A cancer patient’s <a href="https://www.cancer.gov/about-cancer/treatment/types/biomarker-testing-cancer-treatment">therapy can be tailored</a> to the specific type of tumour they have, if only the doctors know what the molecular targets are that will make the drugs effective for that patient. Parents may <a href="https://doi.org/10.1038/npjgenmed.2015.12">finally get a name</a> for the syndrome that their child has been living with. </p>
<p>All of this can be achieved by sequencing the genome of a patient. A genome is <a href="https://www.yourgenome.org/facts/what-is-a-genome">a set of genetic instructions</a> that can be deduced through examining blood or saliva. When scientists sequence genomes, they are involved in interpreting the changes between one individual and another and by determining the changes that explain a disease, provide a diagnosis or predict the best treatment.</p>
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<a href="https://theconversation.com/medical-schools-need-to-prepare-doctors-for-revolutionary-advances-in-genetics-158280">Medical schools need to prepare doctors for revolutionary advances in genetics</a>
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<p>At the University of Toronto, I teach students how to <a href="https://moleculargenetics.utoronto.ca/news/learn-more-about-medgen-professor-dr-martina-steiner">run the experiments to analyze a genome</a>. The students learn how to sequence the genome, what the data looks like and how the results can be used to provide a diagnosis or choose the right medication. Virtual labs or “lab simulations” offer a way to experience the experimental steps for a biological experiment on a screen. Even before the pandemic started, I was experimenting with virtual labs in my classroom. </p>
<h2>Some lab work continued in person</h2>
<p>Virtual labs for genome sequencing, like <a href="https://doi.org/10.1152/advan.00241.2020">virtual labs in some other sciences</a>, offer some advantages and opportunities for student learning. However, virtual labs for genome sequencing are not a replacement for hands-on, wet lab experience (<a href="https://www.universitylabpartners.org/blog/wet-lab-vs-dry-lab-for-your-life-science-startup">where biological matter can be analyzed and tested by using various liquids</a>), and are certainly not replacing in-person training for professional purposes. </p>
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<img alt="Graphic illustration of a person in a lab surrounded by equipment." src="https://images.theconversation.com/files/443337/original/file-20220131-21-166uu4p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/443337/original/file-20220131-21-166uu4p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=630&fit=crop&dpr=1 600w, https://images.theconversation.com/files/443337/original/file-20220131-21-166uu4p.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=630&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/443337/original/file-20220131-21-166uu4p.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=630&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/443337/original/file-20220131-21-166uu4p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=792&fit=crop&dpr=1 754w, https://images.theconversation.com/files/443337/original/file-20220131-21-166uu4p.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=792&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/443337/original/file-20220131-21-166uu4p.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=792&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">‘Wet lab’ experience where students analyze biological matter is important training for professional work.</span>
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<p>Even when other instruction was moved online due to COVID-19, some wet <a href="https://www.utoronto.ca/news/u-t-plans-gradual-safe-return-our-campuses-fall-semester-mix-person-and-virtual-learning">lab courses</a> have continued in person since the summer of 2020. I spoke with <a href="http://biochemistry.utoronto.ca/person/ahlia-khan-trottier/">Ahlia Khan-Trottier</a>, director of the division of teaching labs at the Temerty Faculty of Medicine at the University of Toronto, who relayed that in the pandemic, “lab courses took various paths as decided by the course co-ordinators/departments — some remained fully in person with COVID-19 measures in place, some were hybrid and others moved fully online.”</p>
<p>In my case, a lab course in the department of molecular genetics where the students were going to run a sequencing experiment was postponed. It ran five months later with the necessary COVID-19 measures in place.</p>
<h2>Move to online labs</h2>
<p><a href="https://doi.org/10.1186/s12909-016-0620-6">Studies</a> have shown that virtual genetics labs can enhance comprehension and motivation, thus <a href="https://doi.org/10.1007/s11423-019-09690-3">improving the learning experience</a>. Students click on a tube to open the lid of a vessel or turn the wheel of a virtual pipette — a hand-held device to transfer small amounts of liquids — to transfer reagents from one container to another. No lab coat is required, no expensive machines and no dangerous chemicals. </p>
<p>In a virtual lab, there are no restrictions to the cost of an experiment, whether clinical specimens can be used, and no ethical concerns or biohazards to contend with. Virtual labs are very “forgiving.” Students can start over, <a href="https://www.britannica.com/science/reagent">reagents</a> are abundantly available and the game-like feeling is rewarding.</p>
<p>Virtual labs bridge theory and practice by providing a multimedia connection between abstract concepts and practical execution. Students use their laptop or phone to observe, click, drag and type in response to videos, questions and instructions. </p>
<p>Virtual reactions are instantaneous and students do not have to wait to use shared equipment such as <a href="https://www.genome.gov/about-genomics/fact-sheets/Polymerase-Chain-Reaction-Fact-Sheet">PCR machines</a> — a machine used to heat or cool samples to allow chemical reactions and physical processes to occur at a specified temperature. </p>
<h2>Different kinds of virtual labs</h2>
<p>Many virtual labs are now being mostly run through software or online applications developed by developers that are either accessible for free or can be purchased by institutions. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/9NXkge1hVss?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">About Lab Xchange lab simulations (virtual labs).</span></figcaption>
</figure>
<p>Resources include free simulations and interactive explorations (like <a href="https://www.labxchange.org/library?">LabXchange</a>), as well as more complex open-ended explorations with immersive animations (like <a href="https://wp.labster.com/introduction-to-labster/">Labster</a>). Such virtual labs combine illustrations, explanations, prompt critical thinking and offer incentives through “gamification.”</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/8tvwdSG_7UE?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Labster virtual lab about medical genetics simulation.</span></figcaption>
</figure>
<p>Some colleagues of mine are also working on building tailored virtual labs for their courses. </p>
<h2>Student experience of virtual labs</h2>
<p>Before the pandemic, the grad students who were using virtual labs in my classroom appreciated the added resource but were very clear that virtual labs could not replace a wet-lab experience. One student described the simulation in the virtual lab like a lab tour, where you get to review the workflow and mentally prepare for the wet-lab but are not directly handing equipment.</p>
<p>It takes years of training to become proficiently skilled in clinical and research laboratory techniques. Dealing with the frustrations of getting equipment to work and developing the <a href="https://bento.bio/protocol/biotechnology-101/introduction-to-pipetting/">muscle memory of performing work hands-on</a> cannot be replicated in the virtual platforms now widely available for genomic sequencing, nor <a href="https://www.taylorfrancis.com/chapters/mono/10.4324/9781315042565-6/introduction-making-move-peer-learning-david-boud-ruth-cohen-jane-university-technology-sampson">can the lessons from learning in a group with peers</a>. </p>
<figure class="align-center ">
<img alt="Students are seen in a lab." src="https://images.theconversation.com/files/443336/original/file-20220131-17-12qsupu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/443336/original/file-20220131-17-12qsupu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/443336/original/file-20220131-17-12qsupu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/443336/original/file-20220131-17-12qsupu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/443336/original/file-20220131-17-12qsupu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=504&fit=crop&dpr=1 754w, https://images.theconversation.com/files/443336/original/file-20220131-17-12qsupu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=504&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/443336/original/file-20220131-17-12qsupu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=504&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Learning to troubleshoot challenges with real equipment and learning from a group with peers are both important dimensions of practice in a wet lab.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<h2>Labs in the future</h2>
<p>Still, virtual labs were gaining traction even before the pandemic, and their <a href="https://www.universityworldnews.com/post.php?story=2021041813552894">use has been sped up during pandemic-related remote teaching</a>.</p>
<p>Instructors and students will continue to value the enhancements that come from lab simulations. For my students, the simulations are useful to catch up and fill in any gaps that stem from different backgrounds. </p>
<p>Furthermore, running through a lab on a computer is an excellent way to <a href="https://doi.org/10.1371/journal.pone.0155895">prepare for an in-person lab</a>, when there is little room for mistakes. Some topics in genomics lend themselves particularly well to virtual instruction, for example learning how to effectively search databases for research and how to retrieve information about the genome. </p>
<p>And certainly, students will continue to appreciate the animations and lab simulations that illustrate difficult concepts, where a moving image says more than a thousand words.</p><img src="https://counter.theconversation.com/content/123814/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Martina Steiner received funding from ITIF (The University of Toronto Provost’s Instructional Technology Innovation Fund) to study the integration of virtual labs in a graduate course.</span></em></p>A medical genomics professor reflects on how lab simulations offer some advantages for student learning, but developing the muscle memory of performing hands-on lab work is important.Martina Steiner, Assistant Professor, Teaching Stream, Medical Genomics, University of TorontoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1750332022-01-18T22:15:51Z2022-01-18T22:15:51ZA huge project is underway to sequence the genome of every complex species on Earth<figure><img src="https://images.theconversation.com/files/441212/original/file-20220118-23-1a3v8dy.jpeg?ixlib=rb-1.1.0&rect=50%2C30%2C6659%2C4436&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>The <a href="https://www.earthbiogenome.org">Earth Biogenome Project</a>, a global consortium that aims to sequence the genomes of all complex life on earth (some 1.8 million described species) in ten years, is ramping up. </p>
<p>The project’s <a href="https://www.pnas.org/cc/the-earth-biogenome-project">origins, aims and progress</a> are detailed in two multi-authored papers <a href="https://www.pnas.org/cgi/doi/10.1073/pnas.2115635118">published</a> <a href="https://www.pnas.org/cgi/doi/10.1073/pnas.2115636118">today</a>. Once complete, it will forever change the way biological research is done. </p>
<p>Specifically, researchers will no longer be limited to a few “model species” and will be able to mine the DNA sequence database of any organism that shows interesting characteristics. This new information will help us understand how complex life evolved, how it functions, and how biodiversity can be protected. </p>
<p>The project was first <a href="https://www.pnas.org/content/115/17/4325">proposed</a> in 2016, and I was privileged to speak at its <a href="https://www.nature.com/articles/d41586-018-07279-z">launch</a> in London in 2018. It is currently in the process of moving from its startup phase to full-scale production. </p>
<p>The aim of phase one is to sequence one genome from every taxonomic family on earth, some 9,400 of them. By the end of 2022, one-third of these species should be done. Phase two will see the sequencing of a representative from all 180,000 genera, and phase three will mark the completion of all the species. </p>
<h2>The importance of weird species</h2>
<p>The grand aim of the Earth Biogenome Project is to sequence the genomes of all 1.8 million described species of complex life on Earth. This includes all plants, animals, fungi, and single-celled organisms with true nuclei (that is, all “eukaryotes”).</p>
<p>While model organisms like mice, rock cress, fruit flies and nematodes have been tremendously important in our understanding of gene functions, it’s a huge advantage to be able to study other species that may work a bit differently.</p>
<p>Many important biological principles came from studying obscure organisms. For instance, genes were famously discovered by Gregor Mendel in peas, and the rules that govern them were discovered in red bread mould. </p>
<p>DNA was discovered first in salmon sperm, and our knowledge of some systems that keep it secure came from research on tardigrades. Chromosomes were first seen in mealworms and sex chromosomes in a beetle (sex chromosome action and evolution has also been explored in fish and platypus). And telomeres, which cap the ends of chromosomes, were discovered in pond scum. </p>
<h2>Answering biological questions and protecting biodiversity</h2>
<p>Comparing closely and distantly related species provides tremendous power to discover what genes do and how they are regulated. For instance, in another PNAS paper, coincidentally also <a href="https://newsconcerns.com/australian-dragons-gender-determined-by-epigenetic-differences/">published today</a>, my University of Canberra colleagues and I discovered Australian dragon lizards regulate sex by the chromosome neighbourhood of a sex gene, rather than the DNA sequence itself.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/sex-lives-of-reptiles-could-leave-them-vulnerable-to-climate-change-69567">Sex lives of reptiles could leave them vulnerable to climate change</a>
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</em>
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<p>Scientists also use species comparisons to trace genes and regulatory systems back to their evolutionary origins, which can reveal astonishing conservation of gene function across nearly a billion years. For instance, the <a href="https://www.researchgate.net/publication/8169799_Donner_AL_Maas_RL_Conservation_and_non-conservation_of_genetic_pathways_in_eye_specification_Int_J_Dev_Biol_200448743-53">same genes</a> are involved in retinal development in humans and in fruit fly photoreceptors. And the BRCA1 gene that is mutated in breast cancer is responsible for repairing DNA breaks in plants and animals.</p>
<p>The genome of animals is also far more conserved than has been supposed. For instance, several colleagues and I recently demonstrated that animal chromosomes are 684 million years old. </p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/specks-of-dust-on-the-microscope-slide-no-we-are-looking-at-the-building-blocks-of-our-genome-168784">Specks of dust on the microscope slide? No, we are looking at the building blocks of our genome</a>
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<p>It will be exciting, too, to explore the “dark matter” of the genome, and reveal how DNA sequences that don’t encode proteins can still play a role in genome function and evolution. </p>
<p>Another important aim of the Earth Biogenome Project is conservation genomics. This field uses DNA sequencing to identify threatened species, which includes about 28% of the world’s complex organisms – helping us monitor their genetic health and advise on management.</p>
<h2>No longer an impossible task</h2>
<p>Until recently, sequencing large genomes took years and many millions of dollars. But there have been tremendous technical advances that now make it possible to sequence and assemble large genomes for a few thousand dollars. The entire Earth Biogenome Project will cost less in today’s dollars than the human genome project, which was worth about US$3 billion in total.</p>
<p>In the past, researchers would have to identify the order of the four bases chemically on millions of tiny DNA fragments, then paste the entire sequence together again. Today they can register different bases based on their physical properties, or by binding each of the four bases to a different dye. New <a href="https://www.genome.gov/about-genomics/fact-sheets/DNA-Sequencing-Fact-Sheet">sequencing methods</a> can scan long molecules of DNA that are tethered in tiny tubes, or squeezed through tiny holes in a membrane. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/440995/original/file-20220117-16-19rnlvx.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/440995/original/file-20220117-16-19rnlvx.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/440995/original/file-20220117-16-19rnlvx.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/440995/original/file-20220117-16-19rnlvx.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/440995/original/file-20220117-16-19rnlvx.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/440995/original/file-20220117-16-19rnlvx.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/440995/original/file-20220117-16-19rnlvx.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/440995/original/file-20220117-16-19rnlvx.jpeg?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">Chromosomes consist of long double-helical arrays of the four base pairs whose sequence specifies genes. DNA molecules are capped at the end by telomeres.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<h2>Why sequence everything?</h2>
<p>But why not save time and money by sequencing just key representative species? </p>
<p>Well, the whole point of the Earth Biogenome Project is to exploit the variation between species to make comparisons, and also to <a href="https://www.pnas.org/content/119/4/e2115636118">capture remarkable innovations</a> in outliers. </p>
<p>There is also the fear of missing out. For instance, if we sequence only 69,999 of the 70,000 species of nematode, we might miss the one that could divulge the secrets of how nematodes can cause diseases in animals and plants.</p>
<p>There are currently 44 affiliated institutions in 22 countries working on the Earth Biogenome Project. There are also 49 affiliated projects, including enormous projects such as the <a href="https://www.ccgproject.org/">California Conservation Genomics Project</a>, the <a href="https://b10k.genomics.cn/">Bird 10,000 Genomes Project</a> and UK’s <a href="https://www.darwintreeoflife.org/">Darwin Tree of Life</a> Project, as well as many projects on particular groups such as bats and butterflies.</p><img src="https://counter.theconversation.com/content/175033/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jenny Graves is a member of the Earth Biogenome Project Working Group, and an author on the two PNAS papers. She receives funding for other projects from the Australian Research Council.</span></em></p>The monumental Earth Biogenome Project has galvanised hundreds of geneticists and bioinformaticists from all over the world.Jenny Graves, Distinguished Professor of Genetics and Vice Chancellor's Fellow, La Trobe UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1708562021-12-01T13:35:43Z2021-12-01T13:35:43ZCharting changes in a pathogen’s genome yields clues about its past and hints about its future<figure><img src="https://images.theconversation.com/files/434799/original/file-20211130-14-gx51zb.jpg?ixlib=rb-1.1.0&rect=50%2C100%2C6176%2C4134&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A virus's genes hold a record of where it's traveled, and when.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/global-pandemic-infographic-royalty-free-image/1270842570">imaginima/E+ via Getty Images</a></span></figcaption></figure><p>More than <a href="https://ourworldindata.org/covid-cases?country=%7EOWID_WRL">250 million people worldwide</a> have tested positive for SARS-CoV-2, usually after a diagnostic nose swab. Those swabs aren’t trash once they’ve delivered their positive result, though. For <a href="https://scholar.google.com/citations?user=L7pQoysAAAAJ&hl=en&oi=ao">scientists</a> <a href="https://scholar.google.com/citations?user=aDRW1JMAAAAJ&hl=en&oi=ao">like</a> <a href="https://scholar.google.com/citations?user=9hWmfYoAAAAJ&hl=en&oi=ao">us</a> they carry additional valuable information about the coronavirus. Leftover material from swabs can help us uncover hidden aspects of the COVID-19 pandemic.</p>
<p>Using what are called phylodynamic methods that can track a pathogen’s travels via changes in its genes, researchers are able to pinpoint factors like <a href="https://doi.org/10.1073/pnas.2012008118">where and when outbreaks start</a>, the <a href="https://doi.org/10.1038/s43856-021-00031-1">number of undetected infections</a> and <a href="https://doi.org/10.1038/s41467-020-19346-z">common routes of transmission</a>. Phylodynamics can also aid in understanding and tracking the spread of new pathogen variants, such as the recently detected <a href="https://twitter.com/trvrb/status/1464353224417325066">omicron variant of SARS-CoV-2</a>.</p>
<h2>What’s in a swab?</h2>
<p>Pathogens, just like people, each have a genome. This is RNA or DNA that contains an organism’s genetic code – its instructions for life and the information necessary for reproduction. </p>
<p>It’s now relatively <a href="https://www.nature.com/articles/d42859-020-00103-7">fast</a> and <a href="https://www.genome.gov/about-genomics/fact-sheets/DNA-Sequencing-Costs-Data">cheap</a> to sequence a pathogen’s genome. In Switzerland, <a href="https://bsse.ethz.ch/cevo/research/sars-cov-2/swiss-sars-cov-2-sequencing-consortium.html">a consortium of government and academic scientists</a> that we’re a part of as already extracted viral genome sequences from <a href="https://cov-spectrum.ethz.ch/explore/Switzerland/AllSamples/AllTimes">almost 80,000 SARS-CoV-2 positive swab tests</a>.</p>
<p>By lining up genetic sequences obtained from different patients, scientists can see which positions in the sequence differ. These differences represent mutations, small errors incorporated into the genome when the pathogen copies itself. We can use these mutational differences as clues to reconstruct chains of transmission and learn about epidemic dynamics along the way. </p>
<h2>Phylodynamics: Piecing together genetic clues</h2>
<p><a href="https://doi.org/10.1126/science.1090727">Phylodynamic methods</a> provide a way to describe how mutational differences relate to epidemic dynamics. These approaches allow researchers to get from the raw data about where mutations have occurred in the viral or bacterial genome to understanding all the implications. It might sound complicated, but it’s actually pretty easy to give an intuitive idea of how it works. </p>
<p>Mutations in the pathogen genome get passed from person to person in a transmission chain. Many pathogens acquire lots of <a href="https://doi.org/10.1016/S0169-5347(03)00216-7">mutations over the course of an epidemic</a>. Scientists can summarize these mutational similarities and differences using what’s essentially a family tree for the pathogen. Biologists call it <a href="https://docs.nextstrain.org/en/latest/learn/interpret/how-to-read-a-tree.html">a phylogenetic tree</a>. Each branching point represents a transmission event, when the pathogen moved from one person to another.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/434467/original/file-20211129-19-1niweey.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="diagram of sample to sequence to tree" src="https://images.theconversation.com/files/434467/original/file-20211129-19-1niweey.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/434467/original/file-20211129-19-1niweey.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=225&fit=crop&dpr=1 600w, https://images.theconversation.com/files/434467/original/file-20211129-19-1niweey.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=225&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/434467/original/file-20211129-19-1niweey.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=225&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/434467/original/file-20211129-19-1niweey.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=283&fit=crop&dpr=1 754w, https://images.theconversation.com/files/434467/original/file-20211129-19-1niweey.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=283&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/434467/original/file-20211129-19-1niweey.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=283&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A phylogenetic tree is an approximation of the past transmission chain, based on variations in the pathogen’s genetic sequence.</span>
<span class="attribution"><span class="source">Guinat, Windels, Nadeau</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>The branch lengths are proportional to the number of differences between sequenced samples. Short branches mean little time between branching points – fast transmission from person to person. Studying the length of branches on this tree can tell us about pathogen spread in the past – maybe even before we knew an epidemic was on the horizon.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/434470/original/file-20211129-15-rzms02.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="diagram of hypothetical virus outbreak's phylogenetic tree" src="https://images.theconversation.com/files/434470/original/file-20211129-15-rzms02.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/434470/original/file-20211129-15-rzms02.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=254&fit=crop&dpr=1 600w, https://images.theconversation.com/files/434470/original/file-20211129-15-rzms02.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=254&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/434470/original/file-20211129-15-rzms02.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=254&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/434470/original/file-20211129-15-rzms02.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=319&fit=crop&dpr=1 754w, https://images.theconversation.com/files/434470/original/file-20211129-15-rzms02.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=319&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/434470/original/file-20211129-15-rzms02.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=319&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Pathogen genome sequences can be used to construct phylogenetic trees and estimate hidden epidemic dynamics. Shorter branches stand for quicker transmission.</span>
<span class="attribution"><span class="source">Guinat, Windels, Nadeau</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<h2>Mathematical models of disease dynamics</h2>
<p>Models in general are simplifications of reality. They try to describe core real-life processes with mathematical equations. In phylodynamics, these equations describe the relationship between epidemic processes and the phylogenetic tree. </p>
<p>Take, for example, tuberculosis. It’s the <a href="https://www.who.int/publications/i/item/9789240037021">deadliest bacterial infection in the world</a>, and it is getting even more threatening because of the widespread evolution of antibiotic resistance. If you catch an antibiotic-resistant version of the tuberculosis bacterium, <a href="https://doi.org/10.1186/s40249-016-0214-x">treatment can take years</a>.</p>
<p>To predict the future burden of resistant tuberculosis, we want to estimate how fast it spreads.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/434837/original/file-20211130-14-kaj3am.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="diagram of epidemiological processes in transmission of TB" src="https://images.theconversation.com/files/434837/original/file-20211130-14-kaj3am.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/434837/original/file-20211130-14-kaj3am.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=432&fit=crop&dpr=1 600w, https://images.theconversation.com/files/434837/original/file-20211130-14-kaj3am.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=432&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/434837/original/file-20211130-14-kaj3am.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=432&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/434837/original/file-20211130-14-kaj3am.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=543&fit=crop&dpr=1 754w, https://images.theconversation.com/files/434837/original/file-20211130-14-kaj3am.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=543&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/434837/original/file-20211130-14-kaj3am.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=543&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Epidemiologists work to track infections as the pathogen moves through a population.</span>
<span class="attribution"><span class="source">Guinat, Windels, Nadeau</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>To do this, we need a model that captures two important processes. First, there’s the course of infection, and second, there’s the development of antibiotic resistance. In real life, infected people can infect others, get treatment and, in the end, either be cured or, in the worst case, die from the infection. On top of this, the pathogen can develop resistance.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/434480/original/file-20211129-27-e5whvt.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="diagram of information fed into mathematical model" src="https://images.theconversation.com/files/434480/original/file-20211129-27-e5whvt.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/434480/original/file-20211129-27-e5whvt.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=282&fit=crop&dpr=1 600w, https://images.theconversation.com/files/434480/original/file-20211129-27-e5whvt.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=282&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/434480/original/file-20211129-27-e5whvt.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=282&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/434480/original/file-20211129-27-e5whvt.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=354&fit=crop&dpr=1 754w, https://images.theconversation.com/files/434480/original/file-20211129-27-e5whvt.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=354&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/434480/original/file-20211129-27-e5whvt.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=354&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Phylodynamic models capture real-life epidemiological processes into mathematical equations and parameters.</span>
<span class="attribution"><span class="source">Guinat, Windels, Nadeau</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>We can translate these epidemiological processes into a mathematical model with two groups of patients – one group infected with normal tuberculosis and one with antibiotic-resistant tuberculosis. The important processes – transmission, recovery and death – can happen at different rates for each group. Finally, patients whose infection develops antibiotic resistance move from the first group to the second.</p>
<p>This model does ignore some aspects of tuberculosis outbreaks, such as asymptomatic infections or relapses after treatment. Even so, when applied to a set of tuberculosis genomes, this model helps us <a href="https://doi.org/10.1016/j.epidem.2021.100471">estimate how fast resistant tuberculosis spreads</a>. </p>
<h2>Capturing hidden aspects of epidemics</h2>
<p>Uniquely, phylodynamic approaches can help researchers answer questions in situations where diagnosed cases do not give the full picture. For example, what about the number of undetected cases or the source of a new epidemic? </p>
<p>A good example of this type of genome-based investigation is our recent work on <a href="https://ec.europa.eu/food/animals/animal-diseases/diseases-and-control-measures/avian-influenza_en#hpai-epidemic-20162017">highly pathogenic avian influenza (HPAI)</a> H5N8 in Europe. This epidemic spread to poultry farms and wild birds across <a href="https://doi.org/10.1111/tbed.12861">30 European countries</a> in 2016. In the end, <a href="https://www.bbc.com/news/world-europe-54825971">tens of millions of birds</a> were culled, devastating the poultry industry.</p>
<p>But were poultry farms or wild birds the real driver of spread? Obviously we cannot ask the birds themselves. Instead, phylodynamic modeling based on H5N8 genomes sampled from poultry farms and wild birds helped us get an answer. It turns out that in some countries the pathogen mainly spread from farm to farm, while in others it spread from wild birds to farms. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/433527/original/file-20211123-21-lof9wy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="ducks outside" src="https://images.theconversation.com/files/433527/original/file-20211123-21-lof9wy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/433527/original/file-20211123-21-lof9wy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=381&fit=crop&dpr=1 600w, https://images.theconversation.com/files/433527/original/file-20211123-21-lof9wy.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=381&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/433527/original/file-20211123-21-lof9wy.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=381&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/433527/original/file-20211123-21-lof9wy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=479&fit=crop&dpr=1 754w, https://images.theconversation.com/files/433527/original/file-20211123-21-lof9wy.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=479&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/433527/original/file-20211123-21-lof9wy.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=479&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Phylodynamic models can estimate the number of avian influenza virus transmissions between wild birds and poultry.</span>
<span class="attribution"><span class="source">C. LeGall</span>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
</figure>
<p>In the case of HPAI H5N8, <a href="https://doi.org/10.1101/2021.10.22.465255">we helped animal health authorities focus control efforts</a>. In some countries this meant limiting transmission between poultry farms while in others limiting contact between domestic and wild birds.</p>
<p>More recently, phylodynamic analyses helped evaluate the impact of control strategies for SARS-CoV-2, including the <a href="https://doi.org/10.1073/pnas.2012008118">first border closures</a> and <a href="https://doi.org/10.1038/s41467-020-20235-8">strict early lockdowns</a>. A big advantage of phylodynamic modeling is that it can account for undetected cases. The models can even describe early stages of the outbreak in the absence of samples from that time period. </p>
<p>Phylodynamic models are under intensive development, continuously expanding the field to new applications and larger datasets. However, there are still challenges in extending genome sequencing efforts to undersampled species and regions and upholding <a href="https://doi.org/10.1038/d41586-021-00331-5">rapid public data sharing</a>. Ultimately, these data and models will help everyone gain new insights on epidemics and how to control them.</p>
<p>[<em>The Conversation’s science, health and technology editors pick their favorite stories.</em> <a href="https://theconversation.com/us/newsletters/science-editors-picks-71/?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=science-favorite">Weekly on Wednesdays</a>.]</p><img src="https://counter.theconversation.com/content/170856/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Claire Guinat receives funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 842621.</span></em></p><p class="fine-print"><em><span>Sarah Nadeau receives funding from the Swiss National Science Foundation and ETH Zurich. </span></em></p><p class="fine-print"><em><span>Etthel Windels 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>After a nose swab tests positive for a virus or bacteria, scientists can use the sample’s genetic sequence to figure out where and when the pathogen emerged and how fast it’s changing.Claire Guinat, Postdoctoral Fellow in Computational Evolution, Swiss Federal Institute of Technology ZurichEtthel Windels, Postdoctoral Fellow in Computational Evolution, Swiss Federal Institute of Technology ZurichSarah Nadeau, PhD Student in Computational Evolution, Swiss Federal Institute of Technology ZurichLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1710882021-11-08T17:43:31Z2021-11-08T17:43:31ZStudying the complex genetics behind hair colour reveals how melanin affects us<figure><img src="https://images.theconversation.com/files/430527/original/file-20211105-10391-1qp3549.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C9200%2C3980&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Genetic analysis can reveal how hair gets its colour.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>One of the traits that we usually use to physically describe people is their hair colour. Hair is a useful descriptor because it varies so much among us.</p>
<p>Melanin is the molecule responsible for the many different hair colour tones. It’s also responsible for the colour of our skin and eyes. We inherit these traits from our parents in a complex way. </p>
<p>Understanding how our genetic information can produce different hair colour tones can be as difficult as untangling long hair after not brushing it for several days.</p>
<p>Even though some genes are known to <a href="https://doi.org/10.1038/ng.2007.13">determine hair colour variation</a>, recent studies based on large cohorts of people from the <a href="https://doi.org/10.1038/s41467-018-07691-z">United Kingdom</a> and <a href="https://doi.org/10.1038/s41467-018-08147-0">Latin America</a> have shown that there are more than a dozen genes involved in hair colour. </p>
<p>In a recent paper <a href="https://doi.org/10.1038/s42003-021-02764-0">published in <em>Communications Biology</em></a>, my colleagues and I studied the genes involved in hair colour in a <a href="https://canpath.ca/about/">Canadian cohort</a> of nearly 13,000 individuals of European-related ancestry. Our findings provide insights about genetic variants that may be driving differences in hair colour.</p>
<h2>Types of melanin</h2>
<p>Melanin is produced in a specific cell-type called melanocytes found in skin, eyes and hair follicles. Melanin is also <a href="https://dx.doi.org/10.4103/1673-5374.202928">found in the brain</a>. The type and amount of melanin and how it is distributed in cells is what creates differences in hair, skin and eye colour.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/430804/original/file-20211108-21-1dnmaba.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Micrograph of melanocytes in the epidermis." src="https://images.theconversation.com/files/430804/original/file-20211108-21-1dnmaba.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/430804/original/file-20211108-21-1dnmaba.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=477&fit=crop&dpr=1 600w, https://images.theconversation.com/files/430804/original/file-20211108-21-1dnmaba.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=477&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/430804/original/file-20211108-21-1dnmaba.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=477&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/430804/original/file-20211108-21-1dnmaba.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=600&fit=crop&dpr=1 754w, https://images.theconversation.com/files/430804/original/file-20211108-21-1dnmaba.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=600&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/430804/original/file-20211108-21-1dnmaba.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=600&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Melanocytes produce melanin, which in turn affects skin and hair colour.</span>
<span class="attribution"><a class="source" href="https://dx.doi.org/10.1007/978-981-13-2447-5_3">(Setijanti H.B., Rusmawati E., Fitria R., Erlina T., Adriany R., Murtiningsih)</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Melanoma, a kind of skin cancer, <a href="https://cancer.ca/en/cancer-information/cancer-types/skin-melanoma/what-is-melanoma">consists of an overgrowth of melanocytes in the skin</a>.</p>
<p>There are two main types of melanin in our hair: <a href="https://www.sciencedirect.com/topics/chemistry/eumelanin">eumelanin</a> and <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/pheomelanin">pheomelanin</a>. Eumelanin is also known as the brown-black pigment, whereas pheomelanin is known as the red-orange pigment. People with red hair have much more pheomelanin, people with dark hair have higher levels of eumelanin than pheomelanin, and blonde hair is due to low amounts of both pigments.</p>
<p>The main difference that guides which of the two types of melanin is synthesized is a switch in a protein called the <a href="https://www.uniprot.org/uniprot/Q01726">melanocyte-stimulating hormone receptor</a>, or MC1R. </p>
<p>Variants of the <a href="https://www.ncbi.nlm.nih.gov/gene/4157">gene <em>MC1R</em></a> that lead to a loss of function of the protein can affect the production of pheomelanin. In contrast, there are many genes across our genome involved eumelanin variation, including less damaging genetic variants in the same <em>MC1R</em> gene.</p>
<h2>Untangling genetic complexity</h2>
<p>In our study, we used <a href="https://doi.org/10.1038/s43586-021-00056-9">genome-wide association studies</a> (GWAS, pronounced ghee-was) to identify genetic regions associated with hair colour across our <a href="https://www.genome.gov/genetics-glossary/Autosome">autosomal chromosomes</a>. GWAS identifies overlapping associations in a gene of interest or other <a href="https://www.pnas.org/content/111/17/6131">functional genomic elements</a>. This method also identifies associations in <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/intergenic-region">intergenic regions</a>, the DNA sequences located between genes.</p>
<p>Correlation does not imply causation. Therefore, we also worked on obtaining evidence to <a href="https://doi.org/10.1098/rsob.190221">locate genetic variants within or near genes of interest</a> that are more likely to be causing hair colour variation. This helps us better understand the molecular mechanisms involved in pigmentation.</p>
<p>We identified genetic variants that have been <a href="https://doi.org/10.1038/s41467-018-07691-z">previously reported</a>, such as those damaging the function of MC1R, which can result in less eumelanin production or even switch the production to pheomelanin. Other genetic variants identified that are involved in hair colour and pigmentation in general, do not change the protein’s structure or function. Instead, they regulate the <a href="https://www.yourgenome.org/facts/what-is-gene-expression">expression of the gene</a>, which means that they control how much of a protein is produced. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/430802/original/file-20211108-25-1aomv9t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A hand with vitiligo showing an absence of melanin on the fingers" src="https://images.theconversation.com/files/430802/original/file-20211108-25-1aomv9t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/430802/original/file-20211108-25-1aomv9t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/430802/original/file-20211108-25-1aomv9t.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/430802/original/file-20211108-25-1aomv9t.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/430802/original/file-20211108-25-1aomv9t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/430802/original/file-20211108-25-1aomv9t.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/430802/original/file-20211108-25-1aomv9t.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"></a>
<figcaption>
<span class="caption">Vitiligo is a genetic condition that affects the production of melanin.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>One example is a <a href="https://www.ncbi.nlm.nih.gov/snp/rs12913832?vertical_tab=true#variant_details">genetic variant</a> near the gene <a href="https://www.ncbi.nlm.nih.gov/gene/4948"><em>OCA2</em></a>, in which <a href="https://dx.doi.org/10.1101/gr.128652.111">the gene expression of <em>OCA2</em> decreases</a> in the presence of <a href="https://www.genome.gov/genetics-glossary/Nucleotide">guanine, one of the building blocks of DNA</a>. This results in lower melanin production.</p>
<p>We also tested if the associated regions shared genetic signals with DNA methylation — <a href="https://doi.org/10.1038/npp.2012.112">which can regulate gene expression</a> — in melanocytes. We observed that the DNA methylation state may be a relevant process in regulating pigmentation in some genomic regions. Future investigation is needed to provide concrete evidence on this.</p>
<h2>Pigmentation pathways</h2>
<p>By studying the genetic factors determining hair colour, we can increase our understanding of how pigmentation occurs. This helps us further understand pigmentation diseases and their genetic risk factors, such as the role of pigmentation in <a href="https://doi.org/10.1038/s41588-020-0611-8">cutaneous melanoma</a> and in <a href="https://doi.org/10.1038/ng.3680">vitiligo</a>.</p>
<p>Another interesting application is the improvement of prediction models of hair colour from a DNA source, <a href="https://doi.org/10.1016/j.fsigen.2015.02.003">which has implications for forensic DNA phenotyping in police investigations, which predicts what someone looks like from forensic samples</a>.</p>
<p>Including other population groups in the research of hair colour may help us identify new genes, which can further improve our understanding of pigmentation mechanisms.</p><img src="https://counter.theconversation.com/content/171088/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Frida Lona Durazo 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>Analyzing the genes that determine hair colour can shed light on other conditions that are affected by melanin production, like vitiligo.Frida Lona Durazo, Postdoctoral fellow, Computational Genetics, Université de MontréalLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1652012021-08-01T09:26:29Z2021-08-01T09:26:29ZNigeria isn’t ready to deal with rising COVID-19 cases<figure><img src="https://images.theconversation.com/files/413520/original/file-20210728-13-auulbi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Nigeria must increase its testing capacity to deal with rising COVID-19 cases </span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/health-worker-takes-a-swab-from-a-man-during-a-community-news-photo/1210354602?adppopup=true">Olukayode Jaiyeola/NurPhoto via Getty Images </a></span></figcaption></figure><p><em>With <a href="https://punchng.com/covid-19-nigeria-records-10-cases-of-delta-variant-ncdc/?utm_source=auto-read-also&utm_medium=web&">rising cases</a> of the Delta variant of the SARS-CoV-2 virus in Nigeria, there is heightened concern about how well the country is prepared to deal with them. The Conversation Africa’s Wale Fatade asked public health expert Doyin Odubanjo what Nigeria should do.</em> </p>
<hr>
<h2>What makes the Delta variant different from other COVID-19 variants?</h2>
<p>The variant has now become the main one of concern <a href="https://www.reuters.com/business/healthcare-pharmaceuticals/delta-covid-variant-now-dominant-worldwide-drives-surge-us-deaths-officials-2021-07-16/">globally</a> and is believed to be the cause of the <a href="https://www.bbc.com/news/world-57907681">recent surge</a> in cases seen in Asia and Africa. It is also believed to be behind the rise in cases even in places with good population vaccination rates such as <a href="https://www.usnews.com/news/top-news/articles/2021-07-26/how-the-delta-variant-upends-assumptions-about-the-coronavirus">Israel and the United Kingdom</a>. </p>
<p>The Delta variant, from all available evidence, has mutations that makes it <a href="https://www.yalemedicine.org/news/5-things-to-know-delta-variant-covid">more contagious</a>. It also replicates very quickly, resulting in high viral loads. This can lead to severe illness requiring <a href="https://www.gavi.org/vaccineswork/five-things-we-know-about-delta-coronavirus-variant-and-two-things-we-still-need">hospitalisation</a> and may take longer to clear and achieve a negative COVID-19 test result. </p>
<p>The combination of higher <a href="https://www.gavi.org/vaccineswork/five-things-we-know-about-delta-coronavirus-variant-and-two-things-we-still-need">transmissibility</a> – more people get infected faster – and higher viral load – <a href="https://www.hackensackmeridianhealth.org/HealthU/2021/07/14/3-things-you-need-to-know-about-the-delta-variant/">people get more sick</a> – means that the variant causes more cases per day. Thus it has the tendency to overwhelm the healthcare system, which could run out of bed spaces, oxygen and other essentials.</p>
<h2>How bad is the situation in Nigeria as regards the Delta variant?</h2>
<p>Unfortunately, it is difficult to say. This is because we are failing where surveillance for COVID-19 is concerned. Recent reports show that <a href="https://punchng.com/covid-19-testing-stops-in-13-states-delta-variant-hitting-unvaccinated-nigerians/">13 states </a> have stopped testing for COVID-19 while others are increasingly relying on private laboratories to do the tests at a higher cost. It is impossible to monitor the disease spread or progression without testing.</p>
<p>To make matters worse, to know the impact of the Delta variant, there is a need to go beyond the <a href="https://my.clevelandclinic.org/health/diagnostics/21462-covid-19-and-pcr-testing">polymerase chain reaction</a> (PCR) tests being done or reported. There is a need to do genomic studies – this is a study of what makes up the virus – on the positive cases to know what variant they may be and even monitor the development of new variants. Such genomic studies are not yet being done systematically.</p>
<h2>How prepared is Nigeria to deal with it?</h2>
<p>Nigeria is not in any way prepared to deal with a serious rise in COVID-19 cases as our health system is more challenged than it was before the pandemic. The staff morale is very low and <a href="https://www.dw.com/en/nigeria-saving-lives-amid-the-health-care-crisis/av-57318575">health worker migration</a> is increasing at an alarming rate. Added to that are <a href="https://www.globalcitizen.org/en/content/nigeria-doctors-strike-COVID-19-health-care/?template=next">strike actions</a> or threats. And, perhaps due to the state of the economy, the political will and leadership required to manage the COVID-19 outbreak is fading away.</p>
<p>Worse still, we have not succeeded in engaging the public effectively and consequently have a politically charged environment with a gulf widening between the government and the people. This means that non-pharmaceutical measures like the use of face masks, social distancing and lockdowns may be even more difficult to implement now as people are less likely to cooperate. Attempts to enforce such measures may even result in civil disturbances.</p>
<p>So, Nigeria cannot afford another wave of COVID-19 cases and definitely nothing on the scale of what the Delta variant has caused in <a href="https://www.washingtonpost.com/world/2021/07/21/coronavirus-latest-updates/">other countries</a>.</p>
<h2>What should be done to keep it at bay?</h2>
<p>I do not know if we can talk of keeping it at bay as the Delta variant has already been identified in parts of Nigeria. So, we need to monitor and manage its spread in the country. We must also keep a close watch on our borders to ensure that new cases are not imported. To monitor it will require that our testing capacity is maintained as a public service and is not just left to private laboratories, which will exclude many people because of cost. We must also go the extra mile of doing genomic studies systematically as part of our surveillance.</p>
<p>We must explore community engagement strategies more than ever to get people to make COVID-19 prevention a personal responsibility.</p><img src="https://counter.theconversation.com/content/165201/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Doyin Odubanjo 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>Nigeria must increase its testing capacity and do more genomic studies to deal effectively with the Delta variant of COVID-19.Doyin Odubanjo, Executive Secretary, Nigerian Academy of ScienceLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1617942021-07-12T15:12:42Z2021-07-12T15:12:42ZEquity and access need to be at the forefront of innovation in human genome editing<figure><img src="https://images.theconversation.com/files/409999/original/file-20210706-27-1jgbp0l.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C6500%2C3656&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Genetic therapies may treat previously uncurable conditions, like sickle cell disease.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>In July 2021, after more than two years of study and consultation, the <a href="https://www.who.int/groups/expert-advisory-committee-on-developing-global-standards-for-governance-and-oversight-of-human-genome-editing">World Health Organization’s Expert Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing</a> <a href="https://www.who.int/publications/i/item/9789240030404">released two reports</a>: a <a href="https://www.who.int/publications/i/item/9789240030060">framework for governance</a> and <a href="https://www.who.int/publications/i/item/9789240030381">recommendations</a> on human genome editing. </p>
<p>The governance framework lists a number ethical values and principles, many of which have not been included in previous international reports on human genome editing. The commitments to inclusiveness, fairness, social justice, non-discrimination, solidarity and global health justice inform the content of all three reports.</p>
<p>The committee also addressed research involving both somatic and germline human genome editing.</p>
<p>Somatic human genome editing involves making changes to the DNA of non-reproductive cells. The therapeutic aim is to correct mutations responsible for genetic disease. Germline human genome editing involves making changes to the DNA of reproductive cells. These changes become heritable when the genetically altered cells are used for reproduction. For many, heritable human genome editing is ethically contentious because of its impact on future generations.</p>
<p>As members of the WHO Expert Advisory, we appreciate the challenges in moving forward with human genome editing technology, given our commitment to ensure that this is not just personalized medicine for an elite few.</p>
<h2>Access and equity</h2>
<p>Early in the committee’s deliberations, Francis Collins, director of the National Institutes of Health in the United States, suggested that attention focused on anything other than heritable human genome editing research was a “<a href="https://www.genengnews.com/news/nih-director-backs-moratorium-for-heritable-genome-editing/">distraction</a>.” The WHO did not share this perspective, as reflected in the mandate given to the expert advisory committee. </p>
<p>For the most part, the committee elected to side-step the debate on the permissibility of heritable human genome editing and focus more broadly on issues of access and equity. On advice from the committee, WHO Director-General Tedros Adhanom Ghebreyesus stated that “<a href="https://www.who.int/news/item/26-07-2019-statement-on-governance-and-oversight-of-human-genome-editing">it would be irresponsible at this time for anyone to proceed with clinical applications of human germline genome editing</a>.”</p>
<p>To improve access to information about clinical trials involving somatic human genome editing and to promote equitable access to the potential benefits of research, in August 2019 the committee launched the <a href="https://www.who.int/groups/expert-advisory-committee-on-developing-global-standards-for-governance-and-oversight-of-human-genome-editing/registry">Human Genome Editing Registry</a>. This is a publicly accessible database currently in a pilot phase.</p>
<h2>Sickle cell disease</h2>
<p>Several potential therapies using somatic genome editing are in development, with some currently in clinical trials. </p>
<p>Sickle cell disease is an extremely painful, debilitating disease that currently can only be managed, not cured. The red blood cells of people with sickle cell disease are shaped in the form of a sickle and tend to clog up small veins, interrupting the blood flow to parts of the body and causing excruciating pain. </p>
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<a href="https://theconversation.com/how-our-red-blood-cells-keep-evolving-to-fight-malaria-96117">How our red blood cells keep evolving to fight malaria</a>
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<p>Sickle cell disease is particularly common in areas of the world that have had a high burden of malaria — at least partly because having one gene for sickle cell disease protects against severe malaria. The <a href="https://doi.org/10.1056/NEJMra1510865">incidence of sickle cell disease is higher in tropical countries</a> and is particularly high in parts of Africa and India. Because of global migration — for instance during the transatlantic slave trade - <a href="https://doi.org/10.7189/jogh.08.021103">sickle cell disease now affects people globally</a>. </p>
<p>Because sickle cell disease is a genetic condition linked to one mutation, <a href="https://doi.org/10.1126/scitranslmed.abf2444">it lends itself well to somatic genome editing</a>. Several clinical trials are now under way (see the WHO genome editing registry for examples) and <a href="https://doi.org/10.1056/NEJMoa2031054">early results are promising</a>. The challenge, however, is that future safe and effective genome editing therapies are likely to be expensive and unlikely to be available to most people with sickle cell disease in Africa or India for many years to come.</p>
<h2>Ethical challenges</h2>
<p>The human data and materials that scientists use to develop and test new therapies comes mostly from <a href="https://doi.org/10.1038/538161a">research on men and white people</a>. A direct consequence of this is that innovative therapies are often untested or less well tested in women or people from different ethnic and racial groups. For example, <a href="https://doi.org/10.1056/NEJMsa1507092">cardiac devices were unnecessarily implanted</a> in people of African ancestry in the United States, based on genetic risk factors that predict this disease in white people. </p>
<p>Much of the scientific work leading to therapeutic innovations occurs <a href="https://healthpolicy.usc.edu/wp-content/uploads/2018/01/01.2018_Global20Burden20of20Medical20Innovation.pdf">in wealthier countries</a> with fewer resource constraints, strong health-care systems and stable infrastructure. As a consequence, <a href="https://doi.org/10.1126/science.1115538">innovations often do not accommodate the resource constraints common in poorer countries and poorer communities</a>. </p>
<p>Somatic genome editing interventions risk becoming solidly intertwined with corporate interest and profit motives. This is partly because <a href="https://doi.org/10.1038/s41587-019-0138-7">many aspects of their development have been patented</a>, increasing the cost for others wanting to use practices or materials for therapy design or delivery.</p>
<h2>Fostering innovation</h2>
<p>The WHO governance framework emphasizes ensuring that genome editing therapies are developed and made available equitably, and inclusive of global human genetic diversity. It also encourages critically analyzing the effects of proprietary ownership of genome editing technologies and future therapies. </p>
<p>As well, equitable access means fostering innovation in low- and middle-income countries. An example is the <a href="https://www.wits.ac.za/agtru/">Antiviral Gene Therapy Research Unit</a> based at the University of the Witwatersrand in South Africa. This research team investigates and seeks to develop gene therapy approaches — including genome editing — to alleviate the high burden of hepatitis B. </p>
<p>The WHO framework recommends that somatic genome editing clinical trials not be conducted in countries without effective research regulation and oversight. It also discourages trials in countries where the resultant therapies are likely to be so expensive or require such specialist care, that they are unlikely ever to be made available. Specifically, this means that clinical trials for somatic genome editing innovations should only be conducted in countries where it’s likely that the innovation would be marketed, and where there is robust ethics oversight. </p>
<p>Somatic human genome editing research offers previously unimaginable pathways to alleviating suffering for millions of people living with conditions such as sickle cell disease. Unless specific attention is paid to ensuring the development of affordable innovations that can be implemented across the globe, these benefits may never reach the global poor.</p><img src="https://counter.theconversation.com/content/161794/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jantina De Vries is a member of the WHO Expert Advisory Committee on Developing Global Standards for Governance.</span></em></p><p class="fine-print"><em><span>Françoise Baylis a member of the WHO Expert Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing, a member of a Working Group to inform the development of the WHO Global Guidance Framework to Harness the Responsible Use of the Life Sciences, May to July 2021, and a member of Planning Committee for the Third International Summit on Human Genome Editing’, London, 7-9 March 2022. </span></em></p>Scientists have been eager to edit genomes to eliminate certain diseases. New WHO reports outlines ethical approaches to research and treatment.Jantina de Vries, Associate professor, Medicine, University of Cape TownFrançoise Baylis, Research Professor, Philosophy, Dalhousie UniversityLicensed as Creative Commons – attribution, no derivatives.