tag:theconversation.com,2011:/es/topics/y-chromosome-12892/articlesY chromosome – The Conversation2023-08-24T04:51:52Ztag:theconversation.com,2011:article/2121122023-08-24T04:51:52Z2023-08-24T04:51:52ZThe ‘weird’ male Y chromosome has finally been fully sequenced. Can we now understand how it works, and how it evolved?<p>The Y chromosome is a never-ending source of fascination (particularly to men) because it bears genes that determine maleness and make sperm. It’s also small and seriously weird; it carries few genes and is full of junk DNA that makes it horrendous to sequence. </p>
<p>However, new “<a href="https://www.nature.com/articles/s41592-022-01730-w">long-read</a>” sequencing techniques have finally provided a reliable sequence from one end of the Y to the other. The paper describing this Herculean effort has been <a href="https://www.nature.com/articles/s41586-023-06457-y">published</a> in Nature.</p>
<p>The findings provide a solid base to explore how genes for sex and sperm work, how the Y chromosome evolved, and whether – as predicted – it will disappear in a few million years.</p>
<h2>Making baby boys</h2>
<p>We have known for <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5443938/#">about 60 years</a> that specialised chromosomes <a href="https://theconversation.com/what-makes-you-a-man-or-a-woman-geneticist-jenny-graves-explains-102983">determine birth sex</a> in humans and other mammals. Females have a pair of X chromosomes, whereas males have a single X and a much smaller Y chromosome.</p>
<p>The Y chromosome is male-determining because it bears a gene <a href="https://pubmed.ncbi.nlm.nih.gov/1695712/">called SRY</a>, which directs the development of a ridge of cells into a testis in the embryo. The embryonic testes make male hormones, and these hormones direct the development of male features in a baby boy.</p>
<p>Without a Y chromosome and a SRY gene, the same ridge of cells develops into an ovary in XX embryos. Female hormones then direct the development of female features in the baby girl.</p>
<h2>A DNA junkyard</h2>
<p>The Y chromosome is very different from X and the 22 other chromosomes of the human genome. It is smaller and bears few genes (only 27 compared to about 1,000 on the X).</p>
<p>These include SRY, a few genes required to make sperm, and several genes that seem to be critical for life – many of which have partners on the X.
Many Y genes (including the sperm genes RBMY and DAZ) are present in multiple copies. Some occur in weird loops in which the sequence is inverted and genetic accidents that duplicate or delete genes are common.</p>
<p>The Y also has a lot of DNA sequences that don’t seem to contribute to traits. This “junk DNA” is comprised of highly repetitive sequences that derive from bits and pieces of old viruses, dead genes and very simple runs of a few bases repeated over and over. </p>
<p>This last DNA class occupies big chunks of the Y that literally glow in the dark; you can see it down the microscope because it preferentially binds fluorescent dyes.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/we-discovered-a-missing-gene-fragment-thats-shedding-new-light-on-how-males-develop-147348">We discovered a missing gene fragment that's shedding new light on how males develop</a>
</strong>
</em>
</p>
<hr>
<h2>Why the Y is weird</h2>
<p>Why is the Y like this? Blame evolution.</p>
<p>We have a lot of evidence that 150 million years ago the X and Y were just a pair of ordinary chromosomes (they still are in birds and platypuses). There were two copies – one from each parent – as there are for all chromosomes.</p>
<p>Then SRY evolved (from an ancient gene with another function) on one of these two chromosomes, defining a new proto-Y. This proto-Y was forever confined to a testis, by definition, and subject to a barrage of mutations as a result of a lot of cell division and little repair. </p>
<p>The proto-Y degenerated fast, losing about 10 active genes per million years, reducing the number from its original 1,000 to just 27. A small “pseudoautosomal” region at one end retains its original form and is identical to its erstwhile partner, the X.</p>
<p>There has been great debate about whether this <a href="http://theconversation.com/sex-genes-the-y-chromosome-and-the-future-of-men-32893">degradation continues</a>, because at this rate the whole human Y would disappear in a few million years (as it already has in some rodents).</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/men-are-slowly-losing-their-y-chromosome-but-a-new-sex-gene-discovery-in-spiny-rats-brings-hope-for-humanity-195903">Men are slowly losing their Y chromosome, but a new sex gene discovery in spiny rats brings hope for humanity</a>
</strong>
</em>
</p>
<hr>
<h2>Sequencing Y was a nightmare</h2>
<p>The first draft of the human genome was completed in 1999. Since then, scientists have managed to sequence all the ordinary chromosomes, including the X, with just a few gaps. </p>
<p>They’ve done this using short-read sequencing, which involves chopping the DNA into little bits of a hundred or so bases and reassembling them like a jigsaw.</p>
<p>But it’s only recently that new technology has allowed sequencing of bases along individual long DNA molecules, producing long-reads of thousands of bases. These longer reads are easier to distinguish and can therefore be assembled more easily, handling the confusing repetitions and loops of the Y chromosome.</p>
<p>The Y is the last human chromosome to have been sequenced end-to-end, or T2T (telomere-to-telomere). Even with long-read technology, assembling the DNA bits was often ambiguous, and researchers had to make several attempts at difficult regions – particularly the highly repetitive region.</p>
<h2>So what’s new on the Y?</h2>
<p>Spoiler alert – the Y turns out to be just as weird as we expected from decades of gene mapping and the previous sequencing.</p>
<p>A few new genes have been discovered, but these are extra copies of genes that were already known to exist in multiple copies. The border of the pseudoautosomal region (which is shared with the X) has been pushed a bit further toward the tip of the Y chromosome.</p>
<p>We now know the structure of the centromere (a region of the chromosome that pulls copies apart when the cell divides), and have a complete readout of the complex mixture of repetitive sequences in the fluorescent end of the Y.</p>
<p>But perhaps the most important outcome is how useful the findings will be for scientists all over the world.</p>
<p>Some groups will now examine the details of Y genes. They will look for sequences that might control how SRY and the sperm genes are expressed, and to see whether genes that have X partners have retained the same functions or evolved new ones.</p>
<p>Others will closely examine the repeated sequences to determine where and how they originated, and why they were amplified. Many groups will also analyse the Y chromosomes of men from different <a href="https://www.biorxiv.org/content/10.1101/2022.12.01.518658v2.abstract">corners of the world</a> to detect signs of degeneration, or recent evolution of function.</p>
<p>It’s a new era for the poor old Y.</p><img src="https://counter.theconversation.com/content/212112/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jenny Graves receives funding from the Australian Research Council.</span></em></p>DNA of the male-determining Y chromosome has been completely sequenced end-to-end, and it’s just as weird as we expected. Will we finally be able to understand how it works?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/2121412023-08-23T15:50:07Z2023-08-23T15:50:07ZScientists find the last remnants of the human genome that were missing in the Y chromosome<figure><img src="https://images.theconversation.com/files/544284/original/file-20230823-23-eua6vx.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C3000%2C1994&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/es/image-illustration/xychromosomes-on-background-medical-symbol-gene-559732429">Rost9/Shutterstock</a></span></figcaption></figure><p>More than 20 years ago, the <a href="https://www.nature.com/articles/35057062">human genome was first sequenced</a>. While the first version was full of “holes” representing missing DNA sequences, the genome has been gradually improved in <a href="https://www.science.org/doi/10.1126/science.abj6987">successive rounds</a>. Each has increased the quality of the genome and, in so doing, resolved most of the blank spaces that prevented us from having a complete reading of our genetic material.</p>
<p>The fundamental difficulty researchers faced in reading the genome from end to end is the enormous number of repeated sequences that populate it. The 20,000 or so genes we humans have occupy barely 2% of the entire genome. The remaining 98% is essentially made up of these families of repeated sequences, mobile elements known as <a href="https://www.nature.com/scitable/topicpage/transposons-the-jumping-genes-518/">transposons</a> and retrotransposons, and – to a lesser but functionally important extent – gene expression regulatory sequences. These function as switches that determine when and where genes are turned on and off.</p>
<p>In March 2022, a <a href="https://doi.org/10.1126/science.abj6987">major revision</a> of the genome was published in the journal <em>Science</em>. An <a href="https://www.genome.gov/about-genomics/telomere-to-telomere">international consortium of researchers known as “T2T”</a> (telomere to telomere, which are the ends of chromosomes) used a novel strategy based a type of cell (CHM13) that retains only one copy of each chromosome.</p>
<p>Combined with the latest techniques for sequencing DNA, the researchers managed to add some 200 million letters to the human genome, resolving most of the holes in chromosomes 1 to 22.</p>
<p>The only one left out was the smallest of all the chromosomes we humans have: Y. It’s an exclusively male chromosome that is also the most complex, with repeated sequences of all kinds.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/544280/original/file-20230823-19-lwlf2d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/544280/original/file-20230823-19-lwlf2d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/544280/original/file-20230823-19-lwlf2d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=257&fit=crop&dpr=1 600w, https://images.theconversation.com/files/544280/original/file-20230823-19-lwlf2d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=257&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/544280/original/file-20230823-19-lwlf2d.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=257&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/544280/original/file-20230823-19-lwlf2d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=323&fit=crop&dpr=1 754w, https://images.theconversation.com/files/544280/original/file-20230823-19-lwlf2d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=323&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/544280/original/file-20230823-19-lwlf2d.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=323&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Cell, chromosome, DNA molecule (double helix) and base pairs.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/es/image-vector/diagram-cell-structure-chromosome-dnadeoxyribonucleic-acid-2175697245">Dee-sign/Shutterstock</a></span>
</figcaption>
</figure>
<h2>The Y chromosome, finally complete</h2>
<p>Each of us has <a href="https://www.genome.gov/genetics-glossary/Chromosome">46 chromosomes</a> in our cells, arranged in pairs. There are actually 23 pairs of chromosomes, 22 pairs of autosomal chromosomes (1 to 22) and one pair of sex chromosomes (which can be X or Y).</p>
<p>From each pair of chromosomes we inherit one from our father and one from our mother. Most females have the 46XX chromosome configuration – the last pair of chromosomes, 23, is made up of two copies of the X chromosome. Most males have the 46XY chromosome configuration, meaning that the sex chromosome pair consists of an X and a Y chromosome.</p>
<p>The Y chromosome, present only in males, contains the genes responsible for the development of the male sex organs, in particular the <a href="https://es.wikipedia.org/wiki/SRY">master gene <em>SRY</em></a>, which triggers a cascade of events that eventually converts an initial undifferentiated gonad into the testes, where sperm are produced. In the absence of the <em>SRY</em> gene (as in 46XX females), this primordial gonad eventually develops into the ovaries, where eggs are produced.</p>
<p>The T2T consortium solved the technical problems that prevented the completion of the Y chromosome sequence, and in so doing, discovered 40 previously unknown protein-coding genes. As detailed in an <a href="https://www.nature.com/articles/s41586-023-06457-y">article in the journal <em>Nature</em></a>, this adds 30 million more letters to the length of the total human genome, which would now have 3.23 billion letters. The new reference genome, called T2T-CHM13+Y, has been made available to the entire research community by the authors of the study.</p>
<p>Alongside the complete sequence of the Y chromosome, <em>Nature</em> has published <a href="https://www.nature.com/articles/s41586-023-06425-6">a second study</a> on the sequences of 43 Y chromosomes derived from humans who lived over the last 183,000 years. Their analysis reveals great diversity in both the size and structure of this Y chromosome over the course of evolution. The researchers have detected, among other things, large sequence inversions – DNA fragments that are flipped and inserted upside down.</p>
<p>That we know more about the Y chromosome is great news. Just about a year ago we saw another scientific breakthrough correlating the common loss of the Y chromosome in many cells with <a href="https://theconversation.com/por-que-hay-mas-viudas-que-viudos-187187">a shorter life expectancy for men compared to women</a>. And it is clear that much more valuable information is hidden in the genes.</p>
<h2>The pangenome initiative</h2>
<p>These two new studies significantly increase our knowledge of human DNA, resolving what we have yet to discover about the smallest but most complex chromosome in our genome. They come on the heels of the <a href="https://montoliu.naukas.com/2023/05/21/por-que-necesitabamos-un-pangenoma-humano/">pangenome initiative</a>, which aims to capture the genetic variability that exists among human beings. While we all share a large part of our genome, we differ by approximately 0.1%. This corresponds to a difference of more than 3 million pairs of letters between any two individuals.</p>
<p>With the pangenome initiative, we will no longer have a single reference genome, but hundreds that will more reliably illustrate our genetic similarities and differences. Among other things, this should help us more easily detect gene mutations associated with the thousands of congenital diseases.</p><img src="https://counter.theconversation.com/content/212141/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The contents of this publication and the views expressed are solely those of the author and this document should not be considered as representing an official position of CSIC nor does it commit CSIC to any liability of any kind.</span></em></p>The smallest chromosome in humans, the men-specific Y chromosome, has just been sequenced after considerable hurdles.Lluís Montoliu, Investigador científico del CSIC, Centro Nacional de Biotecnología (CNB - CSIC)Licensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1959032022-12-05T19:05:08Z2022-12-05T19:05:08ZMen are slowly losing their Y chromosome, but a new sex gene discovery in spiny rats brings hope for humanity<figure><img src="https://images.theconversation.com/files/498865/original/file-20221205-12013-wfzmkt.jpg?ixlib=rb-1.1.0&rect=516%2C0%2C4393%2C2813&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">X and Y chromosome.</span> <span class="attribution"><span class="source">Nathan Devery/Shutterstock</span></span></figcaption></figure><p>The sex of human and other mammal babies is decided by a male-determining gene on the Y chromosome. But the human <a href="https://theconversation.com/sex-genes-the-y-chromosome-and-the-future-of-men-32893">Y chromosome is degenerating</a> and may disappear in a few million years, leading to our extinction unless we evolve a new sex gene.</p>
<p>The good news is two branches of rodents have already lost their Y chromosome and have lived to tell the tale.</p>
<p>A new paper in <a href="https://www.pnas.org/doi/10.1073/pnas.2211574119">Proceedings of the National Academy of Science</a> shows how the spiny rat has evolved a new male-determining gene.</p>
<h2>How the Y chromosome determines human sex</h2>
<p>In humans, as in other mammals, females have two X chromosomes and males have a single X and a puny little chromosome called Y. The names have nothing to do with their shape; the X stood for “unknown”. </p>
<p>The X contains about 900 genes that do all sorts of jobs unrelated to sex. But the Y contains <a href="https://www.genome.gov/about-genomics/fact-sheets/Y-Chromosome-facts">few genes (about 55)</a> and <a href="https://genomebiology.biomedcentral.com/articles/10.1186/gb-2003-4-9-226">a lot of non-coding DNA</a> – simple repetitive DNA that doesn’t seem to do anything.</p>
<p>But the Y chromosome packs a punch because it contains an all-important gene that kick-starts male development in the embryo. At about 12 weeks after conception, this master gene switches on others that regulate the development of a testis. The embryonic testis makes male hormones (testosterone and its derivatives), which ensures the baby develops as a boy. </p>
<p>This master sex gene was identified as SRY (sex region on the Y) <a href="https://www.newscientist.com/article/mg12717262-400-science-the-gene-that-makes-a-man-of-you/">in 1990</a>. It works by triggering a genetic pathway starting with a gene called SOX9 which is key for male determination in all vertebrates, although it does not lie on sex chromosomes.</p>
<h2>The disappearing Y</h2>
<p>Most mammals have an X and Y chromosome similar to ours; an X with lots of genes, and a Y with SRY plus a few others. This system comes with problems because of the unequal dosage of X genes in males and females.</p>
<p>How did such a weird system evolve? The surprising finding is that <a href="https://genome.cshlp.org/content/18/6/965.abstract">Australia’s platypus</a> has completely different sex chromosomes, more like those of birds.</p>
<p>In platypus, the XY pair is just an ordinary chromosome, with two equal members. This suggests the mammal X and Y were an ordinary pair of chromosomes not that long ago.</p>
<p>In turn, this must mean the Y chromosome has lost 900–55 active genes over the 166 million years that humans and platypus have been evolving separately. That’s a loss of about five genes per million years. At this rate, the last 55 genes will be gone in <a href="https://www.nature.com/articles/415963a">11 million years</a>.</p>
<p>Our claim of the imminent demise of the human Y <a href="https://core.ac.uk/download/pdf/10638174.pdf">created a furore</a>, and to this day there are claims and counterclaims about the expected lifetime of our Y chromosome – estimates <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139287/">between infinity</a> and <a href="https://www.amazon.com/Adams-Curse-Future-without-Men/dp/0393326802">a few thousand years</a></p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/x-y-and-the-genetics-of-sex-professor-jenny-graves-awarded-the-prime-ministers-prize-for-science-2017-85740">X, Y and the genetics of sex: Professor Jenny Graves awarded the Prime Minister's Prize for Science 2017</a>
</strong>
</em>
</p>
<hr>
<h2>Rodents with no Y chromosome</h2>
<p>The good news is we know of two rodent lineages that have already lost their Y chromosome – and are still surviving.</p>
<p>The mole voles of eastern Europe and the spiny rats of Japan each boast some species in which the Y chromosome, and SRY, have completely disappeared. The X chromosome remains, in a single or double dose in both sexes.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/498837/original/file-20221205-25475-vogco0.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A small brown rodent sitting on leaf litter among branches" src="https://images.theconversation.com/files/498837/original/file-20221205-25475-vogco0.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/498837/original/file-20221205-25475-vogco0.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=440&fit=crop&dpr=1 600w, https://images.theconversation.com/files/498837/original/file-20221205-25475-vogco0.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=440&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/498837/original/file-20221205-25475-vogco0.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=440&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/498837/original/file-20221205-25475-vogco0.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=553&fit=crop&dpr=1 754w, https://images.theconversation.com/files/498837/original/file-20221205-25475-vogco0.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=553&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/498837/original/file-20221205-25475-vogco0.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=553&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The Amami spiny rat (Tokudaia osimensis) is endemic to the Japanese island of Amami Ōshima.</span>
<span class="attribution"><a class="source" href="https://www.global.hokudai.ac.jp/blog/novel-sex-determination-mechanism-revealed-in-mammals/">Asato Kuroiwa</a></span>
</figcaption>
</figure>
<p>Although it’s not yet clear how the mole voles determine sex <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5704219/">without the SRY gene</a>, a team led by Hokkaido University biologist Asato Kuroiwa has had more luck with the spiny rat – a group of three species on different Japanese islands, all endangered.</p>
<p>Kuroiwa’s team discovered most of the genes on the Y of spiny rats had been relocated to other chromosomes. But she found no sign of SRY, nor the gene that substitutes for it.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/498856/original/file-20221205-24-hl2yi5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A young Japanese woman with tortoiseshell glasses smiling at the camera" src="https://images.theconversation.com/files/498856/original/file-20221205-24-hl2yi5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/498856/original/file-20221205-24-hl2yi5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=703&fit=crop&dpr=1 600w, https://images.theconversation.com/files/498856/original/file-20221205-24-hl2yi5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=703&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/498856/original/file-20221205-24-hl2yi5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=703&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/498856/original/file-20221205-24-hl2yi5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=883&fit=crop&dpr=1 754w, https://images.theconversation.com/files/498856/original/file-20221205-24-hl2yi5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=883&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/498856/original/file-20221205-24-hl2yi5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=883&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Asato Kuroiwa leads the lab that discovered the ‘new’ sex determination gene in spiny rats.</span>
<span class="attribution"><a class="source" href="https://www.global.hokudai.ac.jp/blog/novel-sex-determination-mechanism-revealed-in-mammals/">Asato Kuroiwa</a></span>
</figcaption>
</figure>
<p>Now at last they have <a href="https://www.pnas.org/doi/10.1073/pnas.2211574119">published a successful identification in PNAS</a>. The team found sequences that were in the genomes of males but not females, then refined these and tested for the sequence on every individual rat.</p>
<p>What they discovered was a tiny difference near the key sex gene SOX9, on chromosome 3 of the spiny rat. A small duplication (only 17,000 base pairs out of more than 3 billion) was present in all males and no females.</p>
<p>They suggest this small bit of duplicated DNA contains the switch that normally turns on SOX9 in response to SRY. When they introduced this duplication into mice, they found that it boosts SOX9 activity, so the change could allow SOX9 to work without SRY.</p>
<h2>What this means for the future of men</h2>
<p>The imminent – evolutionarily speaking – disappearance of the human Y chromosome has elicited speculation about our future.</p>
<p>Some lizards and snakes are female-only species and can make eggs out of their own genes via what’s known as <a href="http://theconversation.com/is-virgin-birth-possible-yes-unless-you-are-a-mammal-52379">parthenogenesis</a>. But this can’t happen in humans or other mammals because we have at least 30 crucial “imprinted” genes that work only if they come from the father via sperm. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/what-we-learn-from-a-fish-that-can-change-sex-in-just-10-days-129063">What we learn from a fish that can change sex in just 10 days</a>
</strong>
</em>
</p>
<hr>
<p>To reproduce, we need sperm and we need men, meaning that the end of the Y chromosome could herald the extinction of the human race.</p>
<p>The new finding supports an alternative possibility – that humans can evolve a new sex determining gene. Phew!</p>
<p>However, evolution of a new sex determining gene comes with risks. What if more than one new system evolves in different parts of the world?</p>
<p>A “war” of the sex genes could lead to the separation of new species, which is exactly what has happened with mole voles and spiny rats.</p>
<p>So, if someone visited Earth in 11 million years, they might find no humans – or several different human species, kept apart by their different sex determination systems.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/did-sex-drive-mammal-evolution-how-one-species-can-become-two-62535">Did sex drive mammal evolution? How one species can become two</a>
</strong>
</em>
</p>
<hr>
<img src="https://counter.theconversation.com/content/195903/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jenny Graves receives funding from the Australian Research Council. </span></em></p>The human Y chromosome could disappear over time, putting our species in jeopardy. But some rodents have managed just fine without it – and we now know how.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/1867972022-07-14T18:35:13Z2022-07-14T18:35:13ZY chromosome loss through aging can lead to an increased risk of heart failure and death from cardiovascular disease, new research finds<figure><img src="https://images.theconversation.com/files/474141/original/file-20220714-32290-2fajn7.jpg?ixlib=rb-1.1.0&rect=3%2C9%2C2106%2C1404&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Chromosomes change over time, whether through the process of aging or exposure to harmful substances in the environment.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/and-y-chromosomes-royalty-free-image/88179880">Steven Puetzer/The Image Bank</a></span></figcaption></figure><p><em>The <a href="https://theconversation.com/us/topics/research-brief-83231">Research Brief</a> is a short take about interesting academic work.</em></p>
<h2>The big idea</h2>
<p>The Y chromosome can be lost through the process of aging, and this can lead to an increased risk of heart failure and cardiovascular disease, according to a 2022 study my colleagues <a href="https://scholar.google.com/citations?user=hM9Ve60AAAAJ&hl=en">and I</a> published in the journal <a href="https://science.org/doi/10.1126/science.abn3100">Science</a>.</p>
<p>While most women have two X chromosomes, most men have one X and one Y. And many people with Y chromosomes start to lose them in a fraction of the cells in their body as they age.</p>
<p>While loss of the Y chromosome was <a href="https://doi.org/10.1038/1971080a0">first observed in 1963</a>, it was not <a href="https://doi.org/10.1038/ng.2966">until 2014</a> that researchers found an association between loss of the Y chromosome and shorter life span. Y chromosome loss has since been linked to a number of <a href="https://doi.org/10.1038/ng.2966">age-related diseases</a>, such as cancer and Alzheimer’s disease. However, it has been unknown whether this loss is just another benign indicator of aging, like gray hair or skin wrinkles, or whether it has a direct role in promoting disease.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/of7vrIIcTa0?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Over time, the degrading Y chromosome may play an increasingly smaller role in development.</span></figcaption>
</figure>
<p>My colleagues and I wanted to figure out if Y chromosome loss directly causes disease and, if so, how. Historically, the Y chromosome has been difficult to study because much of its genetic material is repetitive – it’s easy to get “lost” trying to decipher the sequence.</p>
<p>However, we were able to take advantage of these repeat sequences by targeting them with the DNA-editing tool <a href="https://medlineplus.gov/genetics/understanding/genomicresearch/genomeediting/">CRISPR</a>. We used CRISPR to introduce breaks into the Y chromosome DNA of white blood cells in mice, destroying and eliminating the Y chromosome. We chose white blood cells in particular because they tend to have a <a href="https://doi.org/10.1038/s41598-020-59963-8">high prevalence</a> of Y chromosome loss.</p>
<p>We found that while loss of the Y chromosome did not have immediate effects on the young mice, they ended up aging poorly, dying at an earlier age than mice that still had Y chromosomes. They also had more buildup of scar tissue in the heart, a condition called <a href="https://doi.org/10.1038%2Fnri1412">fibrosis</a>, as well as a stronger decline in heart function after induced heart failure. Treating the mice with a drug that blocks heart scarring, however, was able to restore lost heart function. </p>
<p>We then evaluated the effects of Y chromosome loss in people. We analyzed data from the <a href="https://www.ukbiobank.ac.uk">U.K. Biobank</a>, a large database of medical and genetic data from 500,000 participants in the U.K. We found that men who had lost their Y chromosomes in over 40% of their white blood cells had a 31% increased risk of dying from cardiovascular disease compared with men who hadn’t lost their Y chromosomes, including a two- to threefold increased risk of dying from congestive heart failure or heart disease. In other words, those with the greatest Y chromosome loss had the greatest risk of death from cardiovascular disease.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/474167/original/file-20220714-32349-yfkrfr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Human karyotype missing a Y chromosome" src="https://images.theconversation.com/files/474167/original/file-20220714-32349-yfkrfr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/474167/original/file-20220714-32349-yfkrfr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=491&fit=crop&dpr=1 600w, https://images.theconversation.com/files/474167/original/file-20220714-32349-yfkrfr.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=491&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/474167/original/file-20220714-32349-yfkrfr.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=491&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/474167/original/file-20220714-32349-yfkrfr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=617&fit=crop&dpr=1 754w, https://images.theconversation.com/files/474167/original/file-20220714-32349-yfkrfr.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=617&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/474167/original/file-20220714-32349-yfkrfr.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=617&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Screening for Y chromosome loss could help lead to earlier treatments for age-related conditions.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/digitally-generated-image-of-karyotype-over-white-royalty-free-image/649121991">Olympia Valla/EyeEm via Getty Images</a></span>
</figcaption>
</figure>
<h2>Why it matters</h2>
<p>Men are reported to have shorter life spans than women in many countries. In industrialized countries like the U.S., this is typically a <a href="https://www.census.gov/library/publications/2020/demo/p25-1145.html">difference of five years</a>. While <a href="https://time.com/5538099/why-do-women-live-longer-than-men/">social, behavioral and other genetic factors</a> may also be at play, they don’t entirely account for the differences in life span.</p>
<p>Our work shows that loss of the Y chromosome can directly contribute to age-related diseases like heart disease through tissue scarring. We believe that a better understanding of how the Y chromosome may contribute to age-related diseases, and potentially the process of aging itself, could lead to ways to screen and prevent excessive tissue scarring that can lead to cardiovascular disease.</p>
<h2>What still isn’t known</h2>
<p>While our study primarily focused on the heart, we also found that mice with Y chromosome loss also had scarring in their kidneys and lungs as well as accelerated cognitive impairment as they aged. Further research can help clarify the role of Y chromosome loss in diseases affecting other parts of the body.</p>
<h2>What’s next</h2>
<p>We are currently searching for specific genes that are lost with the Y chromosome that may be responsible for the disease-causing effects of Y chromosome loss. This information can help us better analyze exactly how loss of the Y chromosome can lead to disease and aid in the development of treatments for it.</p><img src="https://counter.theconversation.com/content/186797/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Kenneth Walsh receives funding from the National Institutes of Health and the National Aeronautics and Space Administration. </span></em></p>The negative health effects of Y chromosome loss could be one potential reason women tend to live longer than men.Kenneth Walsh, Professor of Internal Medicine, University of VirginiaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1631842021-06-27T08:43:44Z2021-06-27T08:43:44ZSex, lies and DNA: why many ‘Bothas’ in South Africa have the wrong surname<figure><img src="https://images.theconversation.com/files/407857/original/file-20210623-27-uljai7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">DNA can solve all sorts of mysteries, including the sometimes thorny question of paternity.</span> <span class="attribution"><span class="source">ktsdesign/Shutterstock</span></span></figcaption></figure><p>Headlines about molecular genetics being used to shed new light on <a href="https://www.nytimes.com/2021/05/22/world/australia/who-was-somerton-man.html">old mysteries</a> or even <a href="https://www.wired.com/story/the-meteoric-rise-of-family-tree-forensics-to-fight-crimes/">put criminals behind bars</a> have become increasingly more common. </p>
<p>In South Africa DNA is being used to answer important questions about everything from a <a href="https://theconversation.com/what-genetic-analysis-reveals-about-the-ancestry-of-south-africas-afrikaners-133242">group of people’s origins</a> to the biological paternity of a child.</p>
<p>But paternity tests aren’t just applicable to modern cases. Fellow researcher Christoff Erasmus and I <a href="https://repository.up.ac.za/bitstream/handle/2263/32007/Greeff_Appel%282013%29.pdf?sequence=1&isAllowed=y">considered</a> DNA evidence to understand a divorce case dating back 321 years. The events before and after the divorce case of Maria Kickers had long-term consequences for a family with a surname that, for decades, appeared often among the country’s white leaders. That name is Botha. </p>
<p>The first prime minister of the <a href="https://www.sahistory.org.za/article/union-south-africa-1910">Union of South Africa</a>, established in 1910, was <a href="https://www.sahistory.org.za/people/louis-botha">Louis Botha</a>. There was also <a href="https://www.sahistory.org.za/people/pieter-willem-botha">PW Botha</a>, the last prime minister to hold that title, and the first to become executive state president of the Republic of South Africa. </p>
<p>Our research shows that Kickers lied in her 1700 divorce case at the Cape of Good Hope. Her lie – about the paternity of her children – led to a chain of events that affected the Botha lineage, resulting in 38 000 people carrying that name when in fact they were descendants of Ferdinandus Appel.</p>
<p>The genetic evidence, which we gathered using a DNA-based paternity test kit, in combination with the documented testimonies, suggests that Ferdinandus Appel was likely the father of Kickers’ first son and Frederik Botha the father of the other boys. When we genotyped a random sample of Botha males. We found that almost half of them have the Appel rather than the Botha Y chromosome.</p>
<p>The false paternity claim means that tens of thousands of Bothas – more than 76 000 South Africans had this surname in 2013 – should in fact be called Appel, a very uncommon name in the country.</p>
<figure class="align-right ">
<img alt="A statue of a man astride a horse, both atop a tan-bricked plinth." src="https://images.theconversation.com/files/408121/original/file-20210624-23-xz6ue8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/408121/original/file-20210624-23-xz6ue8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=917&fit=crop&dpr=1 600w, https://images.theconversation.com/files/408121/original/file-20210624-23-xz6ue8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=917&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/408121/original/file-20210624-23-xz6ue8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=917&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/408121/original/file-20210624-23-xz6ue8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1152&fit=crop&dpr=1 754w, https://images.theconversation.com/files/408121/original/file-20210624-23-xz6ue8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1152&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/408121/original/file-20210624-23-xz6ue8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1152&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A statue of Louis Botha, whose surname, DNA suggests, should have been Appel.</span>
<span class="attribution"><span class="source">Felix Lipov/Shutterstock/For editorial use only</span></span>
</figcaption>
</figure>
<p>If the Kickers divorce case was heard today, DNA evidence would have refuted the lie about paternity outright and the Botha family may well have shattered. Our findings provide another reminder that DNA evidence can clarify events that happened centuries ago, <a href="https://kids.frontiersin.org/articles/10.3389/frym.2020.00106">deepening and improving</a> our understanding of history. </p>
<h2>The divorce case</h2>
<p>One of our sources was a set of <a href="http://www.ballfamilyrecords.co.uk/">records</a> presented by Richard Ball, who is linked to the families at the heart of the divorce case. We also drew information from published genealogical records.</p>
<p>From these we <a href="https://repository.up.ac.za/bitstream/handle/2263/32007/Greeff_Appel%282013%29.pdf?sequence=1&isAllowed=y">pieced together</a> the following events.</p>
<p>Kickers married Jan Cornelitz in 1683 at the Cape. They had seven children – four boys and three girls. Christening records for six of these children have been located; all named Cornelitz as the father. In 1700 Jan filed for divorce, claiming that Maria cheated on him with Ferdinandus Appel as well as a tenant who farmed alongside him, Frederik Botha. </p>
<p>Maria denied any involvement with Ferdinandus Appel, but confessed that Frederik Botha was the biological father of all her children. </p>
<p>In her own defence, she claimed that Jan, her husband, encouraged her relationship with Frederik Botha because Jan was “onbequaamd” – a Dutch word meaning “incompetent”.</p>
<p>Frederik Botha confirmed before the court Maria’s claim that all her children were his. While the court did not find Maria to be licentious, they did not give her permission to remarry. As a result, Maria and Frederik Botha had to wait until Jan died, 14 years later, before they could marry. The children then took on the name Botha.</p>
<h2>The genetic evidence</h2>
<p><a href="https://isogg.org/wiki/Y_chromosome_DNA_tests#:%7E:text=A%20Y%20chromosome%20DNA%20test,unchanged%20from%20father%20to%20son.&text=Y%2DDNA%20tests%20are%20typically,in%20a%20surname%20DNA%20project">Y chromosomes</a> are inherited like surnames. So, any of Maria’s sons’ descendants along an unbroken line of males should carry identical Y chromosomes, bar a few mutations. </p>
<p>With the help of a genealogist we managed to contact and obtain DNA samples from all four of Maria’s sons along unbroken male lines. In three cases, more than one descendent was found. We genotyped these Bothas’ Y chromosomes with a kit that is used for paternity tests. The Y chromosomes clearly separated into two groups distinguished by too many mutations to have stemmed from the same Botha ancestor. Within each group, there were a few mutations between individuals, as one would expect for two Y chromosomes with 11 to 19 ancestors between them. </p>
<p>Interestingly, the one group linked to Maria’s first-born son, whereas the other sons’ descendants all shared virtually identical genetic profiles. This pattern piqued our curiosity as it suggested that the first son’s profile may have stemmed from Ferdinandus Appel.</p>
<p>To test this idea, we genotyped two Appel men: one was a clear match to the first sons’ descendants. It is 130 times more likely that Maria’s first son was fathered by Ferdinandus Appel than by a random male that just happened to have the same Y chromosome profile</p>
<p>When we genotyped a random sample of Bothas we found that almost half of them have the Appel rather than the Botha profile. To understand why the first son seems to account for more than a quarter of modern Bothas, we looked at the male descendants as listed in the genealogical records published by the now-closed Genealogical Institute of South Africa. </p>
<p>Just counting the 62 males that were 30 years old or younger in 1780, 45% descended from the first brother while the other three Botha brothers accounted for the remaining 55%. The high number of the first brother’s descendants in 1780 could thus explain why so many of our random sample grouped with the Appel profile.</p><img src="https://counter.theconversation.com/content/163184/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jaco Greeff receives funding from the NRF. Any opinion, findings and conclusions or recommendations expressed in this material are his and therefore the NRF does not accept any liability in regard thereto. </span></em></p>A lie about children’s paternity back in 1700 means tens of thousands of South Africans today are using the wrong surname.Jaco Greeff, Professor in Genetics, University of PretoriaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1227642019-09-03T13:40:36Z2019-09-03T13:40:36ZStop calling it a choice: Biological factors drive homosexuality<figure><img src="https://images.theconversation.com/files/290563/original/file-20190902-175705-15kuqu2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Biological factors shape sexual preference.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/lgbt-lesbian-couple-moments-happiness-concept-575079754?src=-1-53">Rawpixel.com/SHutterstock.com</a></span></figcaption></figure><p><a href="https://doi.org/10.1126/science.aat7693">Across cultures, 2% to 10% of people report having same-sex relations</a>. In the U.S., <a href="https://www.statista.com/topics/1249/homosexuality/">1% to 2.2% of women and men</a>, respectively, identify as gay. Despite these numbers, <a href="https://www.pewresearch.org/global/2013/06/04/the-global-divide-on-homosexuality/">many people still consider homosexual behavior to be an anomalous choice</a>. However, biologists have <a href="https://us.macmillan.com/books/9780312253776">documented homosexual behavior in more than 450 species</a>, arguing that same-sex behavior is not an unnatural choice, and may in fact play a vital role within populations.</p>
<p>In <a href="https://doi.org/10.1126/science.aat7693">a 2019 issue of Science magazine</a>, geneticist Andrea Ganna at the Broad Institute of MIT and Harvard, and colleagues, described the largest survey to date for genes associated with same-sex behavior. By analyzing the DNA of nearly half a million people from the U.S. and the U.K., they concluded that genes account for between 8% and 25% of same-sex behavior. </p>
<p><a href="https://www.nature.com/news/sex-redefined-1.16943">Numerous studies have established that sex is not just male or female</a>. Rather, it is a continuum that emerges from a person’s genetic makeup. Nonetheless, misconceptions persist that same-sex attraction is a choice that warrants condemnation or <a href="https://www.apa.org/pi/lgbt/resources/just-the-facts">conversion</a>, and leads to discrimination and persecution.</p>
<p><a href="https://wjsulliv.wixsite.com/sullivanlab">I am a molecular biologist</a> and am interested in this new study as it further illuminates the genetic contribution to human behavior. As the author of the book, <a href="https://www.penguinrandomhouse.com/books/608709/pleased-to-meet-me-by-bill-sullivan/9781426220555/">“Pleased to Meet Me: Genes, Germs, and the Curious Forces That Make Us Who We Are,”</a> I have done extensive research into the biological forces that conspire to shape human personality and behavior, including the factors influencing sexual attraction.</p>
<h2>The hunt for ‘gay genes’</h2>
<p>The new finding is consistent with multiple earlier studies of twins that indicated same-sex attraction is a heritable trait.</p>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/290580/original/file-20190902-175663-baya3w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/290580/original/file-20190902-175663-baya3w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=1200&fit=crop&dpr=1 600w, https://images.theconversation.com/files/290580/original/file-20190902-175663-baya3w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=1200&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/290580/original/file-20190902-175663-baya3w.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=1200&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/290580/original/file-20190902-175663-baya3w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1508&fit=crop&dpr=1 754w, https://images.theconversation.com/files/290580/original/file-20190902-175663-baya3w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1508&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/290580/original/file-20190902-175663-baya3w.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1508&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A new study suggests that genes are responsible for between 8% and 25% of same-sex preference.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/dna-multi-color-isolated-on-white-717211195?src=-1-47">Guru 3D</a></span>
</figcaption>
</figure>
<p>The 2019 study is the latest in a hunt for “gay genes” that began in 1993, when Dean Hamer <a href="https://doi.org/10.1126/science.8332896">linked male homosexuality to a section of the X chromosome</a>. As the ease and affordability of genome sequencing increased, additional gene candidates have emerged with potential links to homosexual behavior. So-called <a href="https://doi.org/10.1038/s41598-017-15736-4">genome-wide association studies identified a gene called <em>SLITRK6</em></a>, which is active in a brain region called the diencephalon that differs in size between people who are homosexual or heterosexual.</p>
<p>Genetic studies in mice have uncovered additional gene candidates that could influence sexual preference. A 2010 study <a href="https://doi.org/10.1186/1471-2156-11-62">linked sexual preference to a gene called fucose mutarotase</a>. When the gene was deleted in female mice, they were attracted to female odors and preferred to mount females rather than males. </p>
<p>Other studies have shown that <a href="https://doi.org/10.1038/nature06089">disruption of a gene called <em>TRPC2</em></a> can cause female mice to act like males. <a href="https://doi.org/10.1126/science.1069259">Male mice lacking <em>TRPC2</em></a> no longer display male-male aggression, and they initiate sexual behaviors toward both males and females. Expressed in the brain, <em>TRPC2</em> functions in the recognition of pheromones, chemicals that are released by one member of a species to elicit a response in another.</p>
<p>With multiple gene candidates being linked to homosexuality, it seemed highly unlikely that a single “gay” gene exists. This idea is further supported by <a href="https://doi.org/10.1126/science.aat7693">the new study</a>, which identified five new genetic loci (fixed positions on chromosomes) correlating with same-sex activity: two that appeared in men and women, two only in men, and one only in women.</p>
<h2>How might these genes influence same-sex behavior?</h2>
<p>I find it intriguing that some of the genes from men identified in Ganna’s study are associated with olfactory systems, a finding that has parallels to the work in mice. Ganna’s group found other gene variants that may be linked with sex hormone regulation, which other scientists have previously suggested plays a large role in shaping the brain in ways that influence sexual behavior. </p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/290575/original/file-20190902-175691-1l5i9pk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/290575/original/file-20190902-175691-1l5i9pk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=846&fit=crop&dpr=1 600w, https://images.theconversation.com/files/290575/original/file-20190902-175691-1l5i9pk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=846&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/290575/original/file-20190902-175691-1l5i9pk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=846&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/290575/original/file-20190902-175691-1l5i9pk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1063&fit=crop&dpr=1 754w, https://images.theconversation.com/files/290575/original/file-20190902-175691-1l5i9pk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1063&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/290575/original/file-20190902-175691-1l5i9pk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1063&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Conditions in the uterus during pregnancy are thought to influence the sexual preferences of the child.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/beautiful-pregnant-woman-shopping-bags-outdoors-503149633?src=-1-18">Anna Om/Shutterstock.com</a></span>
</figcaption>
</figure>
<p>Males with a genetic condition called <a href="https://ghr.nlm.nih.gov/condition/androgen-insensitivity-syndrome">androgen insensitivity syndrome</a> can develop female genitalia and are usually brought up as girls, despite being genetically male – with an X and Y chromosome – and they are attracted to men. This suggests that testosterone is needed to “masculinize” a prenatal brain; if that doesn’t happen, the child will grow up to desire men. </p>
<p>Similarly, girls who have a genetic condition called <a href="https://www.nichd.nih.gov/health/topics/cah">congenital adrenal hyperplasia</a> are exposed to unusually high levels of male hormones like testosterone while in the womb, which may masculinize their brain and increase the odds of lesbianism. </p>
<p>It’s also possible that hormonal shifts during pregnancy could affect how a fetus’ brain is configured. In rats, <a href="https://doi.org/10.1210/en.2011-0277">manipulation of hormones during pregnancy</a> produces offspring that exhibit homosexual behavior.</p>
<h2>Why does homosexual behavior exist?</h2>
<p>Several hypotheses have been advanced to explain how homosexuality can be beneficial in perpetuating familial genes. One idea involves the concept of kin selection, whereby people work to ensure the passage of their family’s genes into subsequent generations. Gay uncles and aunts, for example, are “<a href="https://doi.org/10.1177/0956797609359623">helpers in the nest</a>” that help raise other family members’ children to nurture the family tree.</p>
<p>Another idea suggests that homosexuality is a “trade-off trait.” For example, certain genes in women help increase their fertility, but <a href="https://doi.org/10.1111/j.1743-6109.2008.00944.x">if these genes are expressed in a male</a>, they predispose him toward homosexuality.</p>
<p>Sexual behavior is widely diverse and governed by sophisticated mechanisms throughout the animal kingdom. As with other complex behaviors, it is not possible to predict sexuality by gazing into a DNA sequence as if it were a crystal ball. Such behaviors emerge from constellations of hundreds, perhaps thousands, of genes, and how they are regulated by the environment.</p>
<p>While there is no single “gay gene,” there is overwhelming evidence of a biological basis for sexual orientation that is programmed into the brain before birth based on a mix of genetics and prenatal conditions, none of which the fetus chooses.</p>
<p>[ <em>You’re smart and curious about the world. So are The Conversation’s authors and editors.</em> <a href="https://theconversation.com/us/newsletters?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=youresmart">You can read us daily by subscribing to our newsletter</a>. ]</p><img src="https://counter.theconversation.com/content/122764/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Bill Sullivan 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>A new study of nearly 500,000 individuals finds that many genes affect same-sex behavior, including newly identified candidates that may regulate smell and sex hormones.Bill Sullivan, Professor of Pharmacology & Toxicology, Indiana University School of MedicineLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/921842018-03-11T09:02:16Z2018-03-11T09:02:16ZSex: birds do it, bees do it - and fungi do it too. Here’s how, and why it matters<figure><img src="https://images.theconversation.com/files/209695/original/file-20180309-30958-1w7hmly.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The sweet-smelling, fluffy white fungus, _Huntiella moniliformis_, engaging in sexual reproduction in the lab.</span> <span class="attribution"><span class="source">Author supplied</span></span></figcaption></figure><p>Sex is an essential part of life. You, me and almost every other living organism on this planet are only here because two individuals got together at some point in the past to have their genes represented in the next generation. </p>
<p>For many species on earth – especially humans – that’s a pretty inflexible process. There are strict requirements: for instance, having two partners of the opposite sex tends to be indispensable for the production of offspring. </p>
<p>But there are a number of exceptions to this rigidity. Some of the most beautiful and interesting are exemplified by certain species of fungi.</p>
<p>Fungi play a variety of roles in our lives. Some are food sources, like button mushrooms; some are used in the production of cheese, wine, beer and bread. Others have provided humans with antibiotics for almost a century. And still others can cause great harm, wiping out trees by the hectare – or even killing humans.</p>
<p>And of course, like most species, fungi have sex lives. I study the sexual behaviour of <em>Huntiella moniliformis</em>, a sweet-smelling and fluffy white fungus that’s found in plantations all over the world. It’s fairly unique in that it’s unisexual – able to reproduce completely alone. </p>
<p>This makes it potentially very dangerous: even if it’s the only fungus in, say, an entire forest, it can keep mating and reproducing. It gets all the evolutionary benefits of sex, without having to go through all the trouble of finding a mating partner. </p>
<p>If we understand its sex life, we can come up with ways to control, manage or even stop it. That’s important in the case of species like <em>Huntiella moniliformis</em>, because they can infect damaged trees and cause disease. </p>
<h2>Fungal mating strategies</h2>
<p>In humans and most other mammals there is only one way to produce sexual offspring: sexual intercourse between a male and a female. Reptiles and birds often also reproduce heterosexually. </p>
<p>Fungi, meanwhile, can utilise one or more of six different sexual strategies. These range from the fungal equivalent of heterosexuality to changing their mating type as necessary.</p>
<p><strong><a href="http://onlinelibrary.wiley.com/doi/10.1111/j.1469-185X.1949.tb00582.x/pdf">Heterothallism</a></strong>: is like heterosexuality in humans and requires two partners. In humans, having two X chromosomes makes you female; having an X and a Y chromosome makes you male. Some fungi use a similar system but instead of a whole chromosome they use single genes. A fungus with the <em>MAT1</em> gene is of the MAT1 mating type; having the <em>MAT2</em> gene means its mating type is MAT2. </p>
<p>For sex to take place, MAT1 and MAT2 partners need to get together. This means that out of everyone you meet, only half are sexually compatible with you. This severely limits the number of successful partners a fungus can meet in its search for a mate.</p>
<p>So how do they find each other? Smell. Or, at least, something similar: pheromones. These are small molecules that let a MAT1 individual know that a MAT2 individual is close, and vice versa. This ensures that no one wastes time and energy slowly growing towards an incompatible partner. </p>
<p><strong>Primary homothallism:</strong> is when a single fungus has sex completely alone. Instead of having either the <em>MAT1</em> or the <em>MAT2</em> gene, they have both. In this way a single individual can make both pheromones and recognise itself as a partner. There are other forms of self-sex too. Two of these include the ability to change mating type. These systems mimic those of some fish that can switch between male and female, depending on what partners are available. The third relies on having two genomes and is functionally very similar to heterothallism. </p>
<p>The fourth lonely sexual strategy completely changed the way we think about sex in fungi. <strong>Unisexuality</strong> occurs in individuals we would classically have thought to be either MAT1 or MAT2. We would have expected them to need a partner, but they don’t.</p>
<p>My PhD research at the <a href="https://www.fabinet.up.ac.za/">Forestry and Agricultural Biotechnology Institute</a> in South Africa has revealed that unisexual reproduction is possible in <em>H. moniliformis</em>. My supervisors and I have recently <a href="http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0192517">shown</a> that MAT2 individuals are able to secrete both pheromones, despite the absence of the <em>MAT1</em> gene. </p>
<p>This means that a single mating type can recognise itself as a compatible partner and respond appropriately. We are currently working on understanding how this system evolved and whether related species could be manipulated to employ the same strategy.</p>
<h2>Why does this matter?</h2>
<p>There are obvious evolutionary benefits to species having sex. The most obvious is because it ensures a species’ longevity. But there are downsides – not for <em>H. moniliformis</em>, in this case, but for forestry plantations. </p>
<p>Sex combines genes from different individuals and produces genetically unique offspring. In disease causing fungi this has been shown to enable host jumping – the movement from a susceptible host species such as a Pine tree in a plantation, to a previously resistant species, like an indigenous tree in a natural forest. </p>
<p>This means that hosts previously thought to be immune to infection could get infected in the future, and can cause serious disease outbreaks that are difficult to control. </p>
<p>The other downside to sex in fungi like <em>H. moniliformis</em> is that it produces easily dispersible spores. These are often the agent that enhances fungal spread and infection. </p>
<p>Understanding these processes, and the sex lives of fungi like <em>H. moniliformis</em>, can help us find answers to how to control the spread of diseases. This will ultimately mean keeping plantations – and humans – safer.</p><img src="https://counter.theconversation.com/content/92184/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Andi Wilson receives funding from the National Research Foundation (NRF). </span></em></p>Understanding the sex lives of fungi can help in finding answers about disease control.Andi Wilson, PhD: Genetics Candidate, University of PretoriaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/866132017-11-01T03:40:18Z2017-11-01T03:40:18ZNot just about sex: throughout our bodies, thousands of genes act differently in men and women<figure><img src="https://images.theconversation.com/files/192548/original/file-20171031-18683-1s8p972.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">In skin, muscle, fat and more tissues, genes behave differently in men and women. </span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/multiracial-serious-people-lineup-mugshot-standing-399773986?src=_EELAU_D3VIkAFLKUOTd9g-1-1">from www.shutterstock.com </a></span></figcaption></figure><p>Most of us are familiar with the genetic differences between men and women. </p>
<p>Men have X and Y sex chromosomes, and women have two X chromosomes. We know that genes on these chromosomes may act differently in men and women. </p>
<p>But a <a href="https://doi.org/10.1186/s12915-017-0352-z">recent paper</a> claims that beyond just genes on X and Y, a full third of our genome is behaving very differently in men and women. </p>
<p>These new data pose challenges for science, medicine and maybe even gender equity.</p>
<hr>
<p><em><strong>Read more:</strong> <a href="https://theconversation.com/x-y-and-the-genetics-of-sex-professor-jenny-graves-awarded-the-prime-ministers-prize-for-science-2017-85740">X, Y and the genetics of sex: Professor Jenny Graves awarded the Prime Minister’s Prize for Science 2017</a></em> </p>
<hr>
<h2>The human genome</h2>
<p>Men and women have practically the same set of about <a href="https://theconversation.com/how-many-genes-does-it-take-to-make-a-person-64284">20,000 genes</a>. The only physical difference in their genetic make up is in the sex chromosomes. Only males have a Y chromosome. Although the X chromosome is present in both sexes, there are two copies in females and only one in males.</p>
<p>The human Y contains only 27 genes. One of these is the sex-determining region Y gene (<a href="https://ghr.nlm.nih.gov/gene/SRY">SRY</a>), which kick-starts the pathway that causes a ridge of cells in a 12 week-old embryo to develop into a testis. </p>
<p>Until recently, many believed that only the presence or absence of SRY distinguishes men and women.</p>
<p>Writing previously, I pointed out that there are 26 other genes on the Y chromosome, and perhaps another hundred or so genes on the X chromosome that are active in two doses in women and a single dose in men. <a href="https://theconversation.com/differences-between-men-and-women-are-more-than-the-sum-of-their-genes-39490">I speculated</a> that there may be a few hundred more genes directly affected by these X or Y genes, or by the hormones that they unleash. </p>
<p>This new paper suggests I underestimated by a huge margin.</p>
<h2>Genes, proteins and tissues</h2>
<p>Genes are parts of a long string of DNA, and composed of molecules that contain four different bases. The sequences of these bases encode the proteins of the body.</p>
<p>Our 20,000 genes make proteins that do a variety of jobs. Some make the fibres in skin or hair, some make muscles contract, and others carry the oxygen in blood. Many are enzymes that drive basic reactions of turning food into flesh and energy.</p>
<p>Genes work by making copies of themselves; the base sequence of DNA is copied into RNA molecules that engage with cell machinery to churn out protein. The more RNA a gene makes, the more protein will be produced.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/192551/original/file-20171031-18730-od0s8t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/192551/original/file-20171031-18730-od0s8t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=377&fit=crop&dpr=1 600w, https://images.theconversation.com/files/192551/original/file-20171031-18730-od0s8t.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=377&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/192551/original/file-20171031-18730-od0s8t.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=377&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/192551/original/file-20171031-18730-od0s8t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=474&fit=crop&dpr=1 754w, https://images.theconversation.com/files/192551/original/file-20171031-18730-od0s8t.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=474&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/192551/original/file-20171031-18730-od0s8t.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=474&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Around one third of our genes act differently in men and women.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/linvoyage/14922004086/in/photolist-bo4wyM-5dopRY-EWZVj7-NqjsaQ-qC9U1v-CMeR5Z-iZgWXx-pFk19q-c9rcku-j22Zvq-j3e1by-j4NScA-j6yecr-oJBaWw-bpckz9-j6eKMU-aXM1fX-j7Xakj-aUnuZX-j4RbXf-nPo8je-oFYmha-j1DRTL-j59HvW-cVuNTG-cULXxu-diAD2U-wuN8vM-99Uqxt-LeB7TE-KJaSuX-cVv2Nd-8CDB7R-cVuJPS-9b3oW2-iXc6g-nNdw5w-9b9M6W-cVuRPb-cVuVi1-5eRCqt-9b3p3P-omcuj-9b6CY8-2jX9wX-E3TTnh-E6dMep-FhfFiX-Lspxem-aXM8Rx">linvoyage/flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>We can now <a href="http://www.cell.com/cell-reports/fulltext/S2211-1247(15)01491-6">measure the number of RNA copies each gene makes</a>. A really active gene may make thousands of copies, an inactive gene may make only a few, or none at all.</p>
<p>This epigenetic (“over the gene”) regulation of gene activity allows specialisation of different body tissues. Your liver and your brain share the same genes, but express them differently; one subset of genes is active in the liver, and a different subset of genes is active in the brain.</p>
<h2>Activity of genes in men and women</h2>
<p>In their new paper, the authors <a href="https://doi.org/10.1186/s12915-017-0352-z">Gershoni and Pietrokovsk</a> looked at how active the same genes are in men and women. They measured the RNA produced by 18,670 genes in 53 different tissues (45 common to both sexes) in 544 adult post mortem donors (357 men and 187 women).</p>
<p>They found that about one third of these genes (more than 6,500) had very different activities in men and women. Some genes were active in men only or women only. Many genes were far more active in one sex or the other.</p>
<p>A few of these genes showed sex biased activity in every tissue of the body. More commonly, the difference was seen in one or a few tissues.</p>
<p>Most of these genes were not on sex chromosomes: only a few lay on the Y or the X.</p>
<p>How could a third of our genes be differently controlled in men and women? </p>
<p>We now understand that proteins work in extensive networks. Change the amount of one protein produced by one gene, and you change the amounts of all the proteins produced by many genes in a long chain of command.</p>
<p>We also know that hormones have powerful influences on gene activity. For instance, testosterone and estrogen dial up or down many genes in reproductive and body tissues.</p>
<h2>Impact on physical features</h2>
<p>The functions of sex biased genes makes some sense. Most affect the reproductive system, which we know to be very different in men and women. For instance, the new study shows that mammary glands have highest frequency of female-biased gene expression, and testis has the highest frequency of male-biased genes.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/192552/original/file-20171031-18686-xtdkba.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/192552/original/file-20171031-18686-xtdkba.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/192552/original/file-20171031-18686-xtdkba.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/192552/original/file-20171031-18686-xtdkba.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/192552/original/file-20171031-18686-xtdkba.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/192552/original/file-20171031-18686-xtdkba.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/192552/original/file-20171031-18686-xtdkba.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">Your muscle development and hairiness are affected by genes.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/asian-woman-instructor-trainer-showing-how-734666779?src=6eJMPgAT1-5-4R5KRihbmQ-2-47">from www.shutterstock.com</a></span>
</figcaption>
</figure>
<p>Other sex biased genes were involved with skin (particular hairiness), muscle, fat tissue and heart, which could relate to sex differences in body morphology and metabolism. </p>
<p>Confirming an <a href="https://www.nature.com/articles/ncomms3771">earlier report</a>, some sex biased genes were involved in brain function, reopening the debate about differences in male and female behaviour.</p>
<h2>Impact on disease susceptibility</h2>
<p>These new findings could explain why men and women are often differently susceptible to diseases, and suggests treatments need to be based on studies of both sexes.</p>
<hr>
<p><em><strong>Read more:</strong> <a href="https://theconversation.com/medicines-gender-revolution-how-women-stopped-being-treated-as-small-men-77171">Medicine’s gender revolution: how women stopped being treated as ‘small men’</a></em> </p>
<hr>
<p>We have <a href="https://www.ncbi.nlm.nih.gov/books/NBK53393/">long known</a> that many diseases are far more common in men (e.g. Parkinsons) or in women (e.g. Multiple Sclerosis).</p>
<p>This study showed that some sex-biased genes were associated with diseases. For instance, a female-biased gene is implicated in cardiovascular homeostasis and osteoporosis, and a male-biased gene in high blood pressure.</p>
<p>The new study also showed a big difference in expression of a gene previously found to be important for <a href="https://www.ncbi.nlm.nih.gov/pubmed/27267697">drug metabolism</a>, which could explain why men and women may respond quite differently. </p>
<p>The <a href="http://www.ossdweb.org/">Organization for the Study of Sex Differences</a> has campaigned to <a href="https://www.theguardian.com/lifeandstyle/2015/apr/30/fda-clinical-trials-gender-gap-epa-nih-institute-of-medicine-cardiovascular-disease">include women in clinical trials</a>. These results should strengthen their hand.</p>
<p>Like it or not, evidence now shows that men and women differ genetically far more profoundly that we have previously recognised. </p>
<p>What do these new insights mean for our progress toward gender equity? A bad outcome could be appeals to return to outdated sexual stereotypes. A good outcome will be recognition of sex differences in medicine and treatment.</p><img src="https://counter.theconversation.com/content/86613/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jenny Graves receives funding from the Australian Research Council. </span></em></p>Like it or not, evidence now shows that men and women differ genetically far more profoundly that we previously recognised. An analysis from the 2017 winner of the Prime Minister’s Prize for Science.Jenny Graves, Distinguished Professor of Genetics, La Trobe UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/822502017-08-28T20:08:30Z2017-08-28T20:08:30ZFrom the crime scene to the courtroom: the journey of a DNA sample<p>The O.J. Simpson murder trial in 1995 introduced DNA forensics to the public. The case collapsed, partly because the defence lawyers cast doubt on the validity of the evidence thanks to the inappropriate way the samples <a href="http://www.latimes.com/opinion/op-ed/la-oe-0618-morrison-scheck-oj-simpson-20140618-column.html">were handled</a>. </p>
<p>Things have changed since then. There are now safeguards in place to ensure the integrity of the chain of evidence. Laboratory protocols and procedures have also advanced. </p>
<p>By following a piece of evidence from the crime scene to the courtroom, we’ll explain just how DNA is studied in the lab and used in the modern legal system.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/explainer-forensic-science-2817">Explainer: Forensic science</a>
</strong>
</em>
</p>
<hr>
<h2>From the crime scene</h2>
<p>The DNA sample’s journey begins at the crime scene.</p>
<p>There are <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4637504/#B63">several principles</a> that guide DNA evidence collection by the <a href="http://www.abc.net.au/news/2015-08-16/crime-scene-investigation-specialists-reveal-gritty-side-of-jobs/6681316">crime scene examiner</a>. In particular, the avoidance of contamination or DNA degradation, and ensuring the chain of custody. </p>
<p>The risk of contamination (from the collector or other evidence samples) is reduced by using sterile, disposable supplies. Degradation is minimised by drying samples before bagging. </p>
<p>Storing dried samples in <a href="https://www.mcscs.jus.gov.on.ca/english/centre_forensic/InformationforInvestigatorsSubmitters/HandbookofForensicEvidencefortheInvestigator/CFS_handbook.html">paper bags</a> rather than plastic, and maintaining samples at the proper temperature helps preserve the DNA and prevent microbial contamination. </p>
<p>It is also important to plan what to collect and how – sufficient material may be required for independent testing by the defence. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/183541/original/file-20170828-27540-5oq4kn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/183541/original/file-20170828-27540-5oq4kn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=320&fit=crop&dpr=1 600w, https://images.theconversation.com/files/183541/original/file-20170828-27540-5oq4kn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=320&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/183541/original/file-20170828-27540-5oq4kn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=320&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/183541/original/file-20170828-27540-5oq4kn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=402&fit=crop&dpr=1 754w, https://images.theconversation.com/files/183541/original/file-20170828-27540-5oq4kn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=402&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/183541/original/file-20170828-27540-5oq4kn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=402&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Police must ensure samples are not contaminated.</span>
<span class="attribution"><span class="source">James Hereward and Caitlin Curtis</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<h2>To the lab</h2>
<p>When any sample arrives in a lab, the first step is to extract the DNA. </p>
<p>The blood samples analysed in the O.J. Simpson trial were typical of the time when large amounts of DNA were required to conduct testing. Today, small amounts of DNA, known as trace DNA, can be analysed from items such as cigarette butts, hair follicles, saliva, semen, and even <a href="http://www.bbc.com/news/world-us-canada-40855915">faeces</a>.</p>
<p>This is possible because of the invention of a method in the 1980s called the polymerase chain reaction or “<a href="https://www.khanacademy.org/science/biology/biotech-dna-technology/dna-sequencing-pcr-electrophoresis/a/polymerase-chain-reaction-pcr">PCR</a>”, which allows an individual strand of DNA to be replicated many times. This creates thousands of copies until there is enough DNA to conduct tests.</p>
<h2>Analysis begins</h2>
<p>The mainstay of modern DNA identification is <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3561883/">short tandem repeat</a> (STR) markers, which are small sections of DNA that vary by length (the number of repeats). </p>
<p>Multiple STR markers are used to create a DNA profile. They are tested using commercial kits that often incorporate a sex determination test (the <a href="https://link.springer.com/article/10.1007%2FBF01371335?LI=true">amelogenin</a> gene). </p>
<p><strong>Mitochondrial DNA</strong></p>
<p>Another method uses mitochondrial DNA.</p>
<p>Mitochondrial DNA tends to last longer than other types of DNA and is often relied on in cold cases. The sequence of mitochondrial DNA “letters” is passed down from mother to child (with the exception of rare mutations), so mothers and grandmothers share the same DNA sequence as their children (but fathers do not). </p>
<p>This makes mitochondrial DNA useful in identifying missing persons - the bones of Daniel Morcombe <a href="https://www.theguardian.com/world/2014/feb/12/daniel-morcombe-case-mothers-dna-matched-100-with-bone-sample">were identified this way</a>. </p>
<hr>
<p><em><strong>Read more</strong> <a href="https://theconversation.com/ned-kelly-remains-are-positively-identified-but-how-was-it-done-3174">Ned Kelly remains are positively identified … but how was it done?</a></em> </p>
<hr>
<p><strong>The Y chromosome</strong></p>
<p>The Y chromosome is present only in males and is passed from father to son. This makes Y chromosome STR markers a useful tool in situations such as <a href="http://www.kgw.com/news/crime/how-are-rape-kits-processed/449988969">sexual assault cases</a> where male and female DNA samples might be mixed and the male suspect’s identity needs to be established.</p>
<p>In the same way as mitochondrial markers, Y-markers can be used for identification through family matching. The process of <a href="http://www.latimes.com/local/lanow/la-me-familial-dna-20161023-snap-story.html">familial matching</a> in criminal investigations raises <a href="http://criminal.findlaw.com/criminal-rights/familial-dna-searches.html">privacy concerns</a> but is increasingly commonplace. </p>
<p>In one recent incident, it was suggested that the surname of a suspect was identified from records of male <a href="http://www.azcentral.com/story/news/local/phoenix/2016/11/30/how-forensic-genealogy-led-arrest-phoenix-canal-killer-case-bryan-patrick-miller-dna/94565410/">family members</a> in public genetic ancestry databases. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/183556/original/file-20170828-27807-fdmar0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/183556/original/file-20170828-27807-fdmar0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/183556/original/file-20170828-27807-fdmar0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/183556/original/file-20170828-27807-fdmar0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/183556/original/file-20170828-27807-fdmar0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/183556/original/file-20170828-27807-fdmar0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/183556/original/file-20170828-27807-fdmar0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Tests often look for Y chromosome STR markers to establish identity.</span>
<span class="attribution"><span class="source">University of Michigan School of Natural Resources & Environment</span></span>
</figcaption>
</figure>
<h2>DNA databases and sample matching</h2>
<p>Australian law enforcement uses the National Criminal Investigation DNA Database (<a href="https://www.acic.gov.au/our-services/biometric-matching/national-criminal-investigation-dna-database">NCIDD</a>), which is managed by the Australian Criminal Intelligence Commission.</p>
<p>The more records added to the database, the greater the odds of making an accidental match. This is because the number of potential matches increases.</p>
<p>To reduce the risk of false “hits”, genetic profiles can be made more complex. Increasing the number of STRs in each profile reduces the risk of a spurious match because the probability of a match (at 20 markers, for example) is estimated by multiplying the probabilities of each STR marker. </p>
<p>The Australian system originally used nine STR’s and a sex-determination gene. In 2013 this was increased to <a href="https://www.google.com.au/url?sa=t&rct=j&q=&esrc=s&source=web&cd=5&cad=rja&uact=8&ved=0ahUKEwjpjLfGjuLVAhUHnpQKHZ5MAuUQFghIMAQ&url=http%3A%2F%2Fwww.anzpaa.org.au%2FArticleDocuments%2F218%2FDNA%2520Profiling%2520Success%2520Rates%2520ISFG%25202013.pdf.aspx&usg=AFQjCNGQpqd6ZYZrMyKkhZS4KYWsLsmvZA">18 core markers</a>.</p>
<p>Internationally, there are moves towards a standard set of 24 markers (such as <a href="https://www.thermofisher.com/order/catalog/product/4476135">GlobalFiler</a>). With this many markers, the odds of two people having the same profile (twins excepted) are incredibly small. This makes an STR profile a powerful way to exclude suspects as well as making matches. </p>
<h2>In the courtroom</h2>
<p>Modern DNA forensic methods are powerful and sensitive, but great care must be taken to prevent miscarriages of justice. </p>
<p>It is difficult for people to comprehend probabilities like one in a quadrillion, and the presentation of such numbers in court can become prejudicial.</p>
<p>In the case of <em><a href="http://eresources.hcourt.gov.au/showCase/2012/HCA/15">Aytugrul v the Queen</a></em>, DNA evidence was presented as an exclusion percentage of 99.9, and the defence argued that this would indicate certainty of guilt to the jury. </p>
<p>Although the High Court of Australia ultimately allowed the DNA evidence presentation in <em>Aytugrul v the Queen</em>, survey data suggest that the statistical presentation of genetic evidence may affect how it is understood and <a href="http://www.tandfonline.com/doi/abs/10.1080/00450618.2014.992472">used by a jury</a>.</p>
<p>Such issues have lead to <a href="https://www.justice.gov/opa/pr/justice-department-issues-draft-guidance-regarding-expert-testimony-and-lab-reports-forensic">guidelines</a> by the US Department of Justice, among other justice groups, for the language used in forensic testimony and reports.</p>
<p>There’s also a risk that contamination might implicate an innocent person. For that reason, DNA evidence is best used in support of other types of evidence. </p>
<p>In the case of <em><a href="http://guides.sl.nsw.gov.au/c.php?g=671792&p=4729488">R v Jama</a></em>, DNA evidence was the sole basis of the rape case. Only after <a href="http://www.aic.gov.au/media_library/publications/tandi_pdf/tandi506.pdf">16 months’</a> imprisonment was it revealed that the sample taken by the doctor was probably contaminated.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/183562/original/file-20170828-27547-1kkhxr7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/183562/original/file-20170828-27547-1kkhxr7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=500&fit=crop&dpr=1 600w, https://images.theconversation.com/files/183562/original/file-20170828-27547-1kkhxr7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=500&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/183562/original/file-20170828-27547-1kkhxr7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=500&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/183562/original/file-20170828-27547-1kkhxr7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=628&fit=crop&dpr=1 754w, https://images.theconversation.com/files/183562/original/file-20170828-27547-1kkhxr7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=628&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/183562/original/file-20170828-27547-1kkhxr7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=628&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">DNA can now be turned into digital data by massively parallel sequencing machines.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<h2>Forensics in the future</h2>
<p>DNA forensics will continue to evolve.</p>
<p>Take a genetic test that can predict <a href="http://www.fsigenetics.com/article/S1872-4973(12)00181-0/abstract">eye and hair colour</a>: this test examines (or “genotypes”) 24 single letter DNA variants. These are analysed with a statistical model that provides probabilities for hair and eye colour based on a large database that links DNA variants to appearance.</p>
<p>Understanding how DNA is linked to <a href="https://www.newscientist.com/article/mg22129613-600-genetic-mugshot-recreates-faces-from-nothing-but-dna/">facial features</a> has even led to the creation of DNA-based <a href="https://snapshot.parabon-nanolabs.com/">mugshots</a>. </p>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3238019/">“Massively parallel” sequencing</a> machines are also a significant advance. These can turn the approximately 3.2 billion DNA “letters” of the human genome into digital information in a matter of hours. </p>
<p>This opens up all of the information contained in our genetic code to law enforcement. For example, some researchers claim it’s possible to <a href="http://www.reuters.com/article/us-dna-suspects-age-idUSKCN0V31BQ">predict the age of a suspect from a blood sample</a> within a mean error margin of 3.8 years, based on methylation markers in the DNA, and this may be improved with the assistance of <a href="http://www.sciencedirect.com/science/article/pii/S1872497317300388">machine learning</a>. </p>
<p>The more we understand the link between appearance and DNA, the better its predictive power will be. It’s tempting to speculate how the O.J. Simpson trial may have turned out with modern forensic DNA protocols and technology.</p><img src="https://counter.theconversation.com/content/82250/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Genetic evidence has become a critical aspect of modern criminal investigations. What are the methods and approaches used in present-day DNA forensics?Caitlin Curtis, Honorary Research Fellow, The University of QueenslandJames Hereward, PostDoc Ecological and Evolutionary Genetics, The University of QueenslandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/394902015-07-30T20:15:42Z2015-07-30T20:15:42ZDifferences between men and women are more than the sum of their genes<figure><img src="https://images.theconversation.com/files/89607/original/image-20150724-3647-jx0xfk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">It's naive to pretend there are no profound genetic and epigenetic differences between the sexes.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/srslymark/3139392279/">Elephant Gun Studios/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span></figcaption></figure><p>Gender differences and sexual preferences are frequently a point of conversation. What produces the differences between men and women? Are they trivial or profound? Are they genetic or environmental, or both? </p>
<p>Some people claim that, genetically, men are <a href="http://www.theregister.co.uk/2010/01/14/chimp_genome_y_chromosome_gumble">more closely related to male chimpanzees</a> than to women. Others discount sex differences because they’re determined by a single gene, called SRY, on the Y chromosome. </p>
<p>But the key to difference between men and women – and chimps – lies not just in the number of their differing genes but in what these genes do.</p>
<h2>A little background</h2>
<p>Let me first explain a bit about genes and chromosomes. Mammals (all vertebrates, in fact) share pretty much the same collection of about 20,000 genes. Each of these is a short stretch of DNA whose base sequence is copied into RNA, and then translated into a protein. </p>
<p>Our 20,000 genes are arrayed on about a metre of DNA (the genome), which is cut up into smaller pieces, which we can see down a microscope as chromosomes when they coil up to divide. The base sequence of genes can differ slightly from person to person, and differ a lot from species to species.</p>
<p>We all have two copies of the genome, one from mother and one from father, so there are two copies of each chromosome – except for the sex chromosomes. Women have two X chromosomes. Men have a single X (from their mother) and the male-specific Y (from their father). The genetic differences between men and women lie in these sex chromosomes. </p>
<p>The X bears more than 1,000 genes. But the Y has only 45, which are <a href="http://www.ncbi.nlm.nih.gov/pubmed/16530039">all that are left</a> of a once ordinary pair of chromosomes that differentiated to be the X and the Y. One of these 45 Y-borne genes (SRY) determines that a baby with XY chromosomes will develop as a boy.</p>
<p>But the Y chromosome is not all male-specific; 24 genes in its top little bit are shared with the X. These are unlikely to cause differences because they’re present in both sexes. </p>
<h2>Difference and the Y chromosome</h2>
<p>The rest of <a href="http://theconversation.com/sex-genes-the-y-chromosome-and-the-future-of-men-32893">the Y lost most of its genes</a> over 150 million years of evolution. A few still cling on, but they’re fatally damaged by mutation, so we can’t count these inactive “pseudogenes”. Indeed, there are only 27 active protein-coding genes on the male-specific part of the Y, although several are present in multiple copies (most of which are inactive). </p>
<p>Nor can we count all 27 because at least 17 have copies on the X chromosome too. Most of these 17 <a href="http://www.nature.com/nature/journal/v508/n7497/full/nature13206.html">remain dedicated</a> to their original purpose, backed up by their X copy. Only three have diverged to <a href="http://www.nature.com/nature/journal/v346/n6281/abs/346240a0.html">acquire male-specific properties</a>, such as <a href="http://www.ncbi.nlm.nih.gov/pubmed/10391206">making sperm</a>.</p>
<p>The remaining ten genes on the human Y have no copy on the X. They are specific to males, so could contribute to differences between men and women. Some of them started off as copies of genes on the X but diverged far from their original function and acquired male-specific roles. Three originated as copies of genes on other chromosomes that were important for male functions.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/89146/original/image-20150721-24286-16xjfkz.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/89146/original/image-20150721-24286-16xjfkz.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/89146/original/image-20150721-24286-16xjfkz.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/89146/original/image-20150721-24286-16xjfkz.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/89146/original/image-20150721-24286-16xjfkz.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/89146/original/image-20150721-24286-16xjfkz.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/89146/original/image-20150721-24286-16xjfkz.jpeg?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">
<figcaption>
<span class="caption">Many obvious differences between humans and chimps, like hairiness, may result from tiny alterations in one or a few genes.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/slightlyblurred/558000935/in/photolist-RiUeM-6P3si-4uhjG6-52yGZ8-qYjxE-7kWvYp-gLQhtK-9AXm4j-mNxeKR-ekynNF-8VyDXi-qYfNZ-8Go7dD-akAJLD-ekEhjW-9KDnq1-8Eoo8-4J9knx-8VAkLk-akkcax-a7thv8-48H5hV-33oZrf-5KWrJu-eAStQu-7gUS5e-4Q9c8y-zZ1P-5E4jTK-8hcfvW-qCmt4K-e9UKZp-qYfNX-arJixA-9KnNvq-5KSdGp-dKUnC-anFCTb-ed6MrT-rhFPRX-ajHCXZ-8g2VLa-8j31Xb-5KSd3V-rwRaVE-52zhxr-5KWsXC-dKUnP-9Z9bpD-989DZL">Willard Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>So the total number of genes possessed by men and completely absent from women may be as low as 13 (and no greater than 27) out of a total of 20,000 human genes. This proportion is clearly <a href="http://genome.cshlp.org/content/15/12/1746.full">not the equivalent to the supposed 4% genomic difference</a> between men and male chimps.</p>
<h2>‘Junk DNA’ on the Y</h2>
<p>A lot of the DNA of the Y chromosome doesn’t code for proteins and has been regarded as junk, sequences that were left over from old viruses and repeated many times. But hidden in this junk are sequences that are <a href="http://www.ncbi.nlm.nih.gov/pubmed/24296535">copied into long RNA molecules</a> but are not translated into protein. </p>
<p>We’re identifying more and more of these non-coding genes, some of which have remained the same in all vertebrates and presumably have some function. At least some non-coding Y genes may have important roles in regulating sex differentiation genes, though this has not yet been demonstrated.</p>
<p>Even more intriguing is new evidence that among the junk DNA on the Y chromosome of the bull are sequences that work to skew the ratio of sperm that bear the Y chromosome, favouring the birth of male calves. When these sequences are deleted, the skewing goes the opposite way, favouring female calves. </p>
<p>This suggests that the X chromosome, too, has some tricks to get preferentially into sperm. It seems there’s <a href="http://www.scientificamerican.com/article/a-battle-of-the-sexes-is-waged-in-the-genes-of-humans-bulls-and-more/?WT.mc_id=SA_BS_20150703">an arms race in the genome of every mammal</a> as these “sexually antagonistic” genes battle it out. There are many sexually antagonistic genes, <a href="http://theconversation.co.born-this-way-an-evolutionary-view%20of-gay-genes-s6051/">possibly including “gay genes”</a> that influence mate choice.</p>
<h2>X genes and sex differences</h2>
<p>A rarely recognised difference between the genomes of men and women is the different copy number of the more than 1,000 protein-coding genes on the X chromosome. There are two copies of these in women and one in men. </p>
<p>Differences in X gene dosage have been ignored because they were supposedly compensated for by a mechanism that silences all the genes on the whole of the X chromosome in females. Known as <a href="http://www.ncbi.nlm.nih.gov/pubmed/21643983">X chromosome inactivation</a>, this mechanism silences one or other X in the cells of the embryo, and this silencing is passed on into groups of cells in the adult. </p>
<p>This “epigenetic” silencing doesn’t change the base sequence of the DNA. But it changes the way the DNA binds to other molecules so it can’t be copied into RNA, and so produces no protein product.</p>
<p>But now we know that <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2911101">more than 150 genes escape inactivation</a> on the human – but not the mouse – X. And independent of sex, the number of X chromosomes has <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2669494">profound effects on some basic metabolic pathways</a>, such as fat and carbohydrate synthesis, which may underlie sex differences in susceptibility to many diseases. Mice that have two X chromosomes are fatter than mice with only one, for instance, even if they have been altered so that they’re male.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/89147/original/image-20150721-24270-1v3qthd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/89147/original/image-20150721-24270-1v3qthd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/89147/original/image-20150721-24270-1v3qthd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/89147/original/image-20150721-24270-1v3qthd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/89147/original/image-20150721-24270-1v3qthd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/89147/original/image-20150721-24270-1v3qthd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/89147/original/image-20150721-24270-1v3qthd.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">There’s a supposed 4% genetic difference between chimps and men.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/animalrescueblog/17080088705/in/photolist-daVK98-daV5dJ-daVfVf-daVNEs-daV1HK-daVnwD-daVanz-daVhsW-daV7G5-daV9s7-daVHk2-daVAk1-daVcsF-daVaWL-daVwBB-daVqWT-daVhct-s2iVj2-fDPzfu-oCjMXd-5LFr83-8YJ451-fDPAUQ-fDPCyJ-h9YQx-feYyLJ-6RrB-6AS2xL-nLy7zj-nLJh8F-7emYiv-daVnzd-daVDKS-8e66aV-daVriN-djQ1zk-bpNmoY-hAHFGV-6jZjU-bDDgda-bqJkS3-bq32sq-c6yNs1-c6AjkW-fTxJ4a-s2bgjL-feHPbR-fDPUnf-feJgKV-feY7uS">International Fund for Animal Welfare Animal Rescue Blog/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>These 150 “escapee” X genes brings us to about 163 genes that are either male-specific, or are active in different doses in men and women. </p>
<h2>What the different genes do</h2>
<p>It’s naïve to think that these 163 genes will all have the same level of influence. Some will code for proteins that are critical for life, or for sex. Others might have only a minor effect, or no visible effect at all.</p>
<p>In fact, the effects of at least some of these 163 genes are profound. The male-determining SRY gene, for instance, kick-starts a <a href="http://www.ncbi.nlm.nih.gov/pubmed/17237341">cascade of dozens of genes</a> that are either turned on in male embryos or turned off in female embryos during testis or ovary development. </p>
<p>Most of these genes are not on sex chromosomes, so they are present in both sexes. But they are turned on to different extents – or at different times or in different tissues – in males and females. Counting these brings up the total to over a 1% genomic difference between the sexes.</p>
<p>What’s more, the downstream effects of SRY are much more profound than simply testis determination. Male hormones, such as testosterone, are synthesised by the embryonic testis and have far-flung effects all over the developing body. Androgens <a href="http://www.ncbi.nlm.nih.gov/pubmed/20399963">turn on hundreds (maybe thousands) of genes</a> that determine male genitalia, male growth, hair, voice and elements of behaviour.</p>
<p>If we count these, we are getting near 800 out of 20,000 human genes, which is closer to the 4% difference of men and male chimpanzees.</p>
<h2>Humans and chimps</h2>
<p>But this often-quoted difference is an average over the whole genome, only a minority of which consists of genes that code for proteins. It tells us little about which genetic differences are important. </p>
<p>Many obvious differences between humans and chimps, such as hairiness and perhaps even speech, may result from tiny alterations in one or a few genes. Differences in timing, or minor regulatory differences, may have massive effects on growth and development. </p>
<p>It’s naive to pretend there are no profound genetic and epigenetic differences between the sexes. But we’re not going to settle issues of how far-reaching the biological differences are just by counting gene differences. How these genes are regulated and their downstream effects are what make the difference between men and chimps, or men and women.</p><img src="https://counter.theconversation.com/content/39490/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jenny Graves received funding from ARC and NHMRC for research into sex chromosome evolution.</span></em></p>What produces the differences between men and women? Are they trivial or profound? Are they genetic or environmental, or both? And are men really closer genetically to chimpanzees than to women?Jenny Graves, Distinguished Professor of Genetics, La Trobe UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/328932014-11-14T03:22:32Z2014-11-14T03:22:32ZSex, genes, the Y chromosome and the future of men<figure><img src="https://images.theconversation.com/files/61612/original/77bxk62d-1413256916.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The human Y chromosome has retained only 3% of its ancestral genes. So why's it a shadow of its former self?</span> <span class="attribution"><a class="source" href="http://www.flickr.com/photos/andercismo/2349098787">Rafael Anderson Gonzales Mendoza/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-sa/4.0/">CC BY-NC-SA</a></span></figcaption></figure><p>The Y chromosome, that little chain of genes that determines the sex of humans, is not as tough as you might think. In fact, if we look at the Y chromosome over the course of our evolution we’ve seen it shrink at an alarming rate.</p>
<p>So will it one day completely disappear? And what happens to the human race if it does? It’s a topic that’s long been debated and we’ve <a href="https://theconversation.com/despair-not-blokes-theres-hope-for-the-y-chromosome-yet-5490">covered before</a> – but a paper <a href="http://www.nature.com/nature/journal/v508/n7497/full/nature13206.html">published in Nature</a> this year suggests the degradation of the chromosome has stabilised.</p>
<p>Humans, like other mammals, have what’s called “chromosomal sex”. Women have two copies of a medium-sized chromosome called X (which stands for “unknown” because it was originally a mystery). Males have a single X and a tiny Y.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/62610/original/bv9fpsk3-1414040470.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/62610/original/bv9fpsk3-1414040470.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/62610/original/bv9fpsk3-1414040470.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=418&fit=crop&dpr=1 600w, https://images.theconversation.com/files/62610/original/bv9fpsk3-1414040470.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=418&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/62610/original/bv9fpsk3-1414040470.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=418&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/62610/original/bv9fpsk3-1414040470.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=525&fit=crop&dpr=1 754w, https://images.theconversation.com/files/62610/original/bv9fpsk3-1414040470.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=525&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/62610/original/bv9fpsk3-1414040470.png?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"></a>
<figcaption>
<span class="caption"></span>
<span class="attribution"><span class="source">Jenny Graves</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>The X bears about 1,600 genes with varied functions. But the Y has hardly any genes; maybe 50, and only 27 of these are in the male-specific part of the Y. Many are present in multiple copies, most of them inactive, lying in giant loops of DNA. Most of the Y is made of repetitive “junk DNA”. Thus the human Y shows all the signs of a degraded chromosome near the end of its life. </p>
<p>But the Y must contain a gene that determines maleness, because XXY people are male, and XO people with a single X but no Y are female.</p>
<p>We know that at 12 weeks an XY human embryo develops testes, which make male hormones and cause a baby to develop as a male. The identity of this male-determining gene on the Y – the SRY gene – was <a href="http://www.ncbi.nlm.nih.gov/pubmed/3144651">discovered in 1990</a> by a young Australian postdoc Andrew Sinclair (a PhD graduate from my lab). Babies with mutations in the SRY gene don’t develop testes, and develop as females.</p>
<h2>Sex in other vertebrates</h2>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/61625/original/5hxvsczs-1413261780.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/61625/original/5hxvsczs-1413261780.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/61625/original/5hxvsczs-1413261780.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/61625/original/5hxvsczs-1413261780.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/61625/original/5hxvsczs-1413261780.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/61625/original/5hxvsczs-1413261780.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/61625/original/5hxvsczs-1413261780.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/61625/original/5hxvsczs-1413261780.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"></a>
<figcaption>
<span class="caption"></span>
<span class="attribution"><a class="source" href="http://www.flickr.com/photos/chilledsalad/216439217">_marmota/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-sa/4.0/">CC BY-NC-SA</a></span>
</figcaption>
</figure>
<p>Leave humans for a moment, and you see a huge variety of sex systems. </p>
<p>Some reptiles, fish and frogs are XX female: XY male like humans, but have different sex genes. Other vertebrates, such as birds and snakes, are just the opposite, with ZZ males and ZW females, and the sex gene is different again. </p>
<p>Many reptiles and some fish use environmental cues (usually temperature) rather than genetic triggers to determine sex.</p>
<p>So we are wrong if we think sex determination in human babies is typical of vertebrates.</p>
<h2>The degrading human Y</h2>
<p>But back in the world of humans: what befell the Y to make it so much smaller than the X and lose most of its genes?</p>
<p>Our sex chromosomes were once just a pair of ordinary chromosomes, which they still are in birds and reptiles. We found they are still ordinary chromosomes <a href="http://onlinelibrary.wiley.com/doi/10.1002/dvdy.23887/full">even in monotreme mammals</a> (platypuses and echidnas) which last shared a common ancestor with humans 166 million years ago.</p>
<p>This means that within the past 166 million years the human Y lost most of its 1,600-odd genes, a rate of nearly 10 per million years.</p>
<p>At this rate, the Y chromosome will disappear in about 4.5 million years. This back-of-the-envelope calculation, inserted as a throwaway line in <a href="http://www.nature.com/nature/journal/v415/n6875/full/415963a.html">a little paper in 2002</a>, produced a hysterical reaction and <a href="http://www.randomhouse.com.au/books/bryan-sykes/adams-curse-a-future-without-men-9780552161930.aspx">loads</a> of <a href="http://books.google.com.au/books/about/Y.html?id=1GaDLsOF-8QC&redir_esc=y">responses</a>. When I talk about the disappearing Y, men in the audience shrink into their seats to protect their manhood.</p>
<figure class="align-left zoomable">
<a href="https://images.theconversation.com/files/62680/original/d7j5r8dp-1414101245.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/62680/original/d7j5r8dp-1414101245.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/62680/original/d7j5r8dp-1414101245.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=593&fit=crop&dpr=1 600w, https://images.theconversation.com/files/62680/original/d7j5r8dp-1414101245.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=593&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/62680/original/d7j5r8dp-1414101245.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=593&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/62680/original/d7j5r8dp-1414101245.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=745&fit=crop&dpr=1 754w, https://images.theconversation.com/files/62680/original/d7j5r8dp-1414101245.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=745&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/62680/original/d7j5r8dp-1414101245.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=745&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption"></span>
<span class="attribution"><a class="source" href="http://www.flickr.com/photos/santarosa/61290146">Santa Rosa OLD SKOOL/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>But why the surprise? Degradation is typical of all sex chromosome systems. Acquisition of a gene that determines sex is the kiss of death for a chromosome, because other genes nearby on the Y evolve a male-specific function, and these genes are kept together by suppressing exchange with the X. </p>
<p>This means that the Y can’t get rid of mutations or deletions or invading junk DNA by swapping good bits with the X.</p>
<p>The poor Y chromosome is also at a disadvantage because it is in the testis every generation. This is a dangerous place to be because cells must divide many times to make sperm, so mutations are much more frequent.</p>
<h2>Has the human Y stabilised?</h2>
<p>Of course, the loss of genes from the Y is unlikely to be linear. It could get faster as the Y becomes more unstable, or it could stabilize as the Y is stripped to [essential genes](http://www.cell.com/cell/abstract/S0092-8674(06%2941-8).</p>
<p>Biologist David Page’s group from Boston keenly defend the honour of the human Y, noting that although chimpanzees have lost a few genes since we shared a common ancestor 5 million years ago, humans haven’t. In fact, humans have lost very few genes in the 25 million years since we diverged from monkeys.</p>
<p>So has the human Y finally stabilised? Maybe loss of any of the remaining 27 Y genes would compromise the viability, or fertility of the bearer. A 2014 paper from Page’s group claiming that the <a href="http://www.nature.com/nature/journal/v508/n7497/full/nature13206.html">Y is here to stay</a> has unleashed another round of debate, <a href="http://www.npr.org/blogs/health/2014/07/28/334490208/with-mens-y-chromosome-size-really-may-not-matter">recently aired</a> on US National Public Radio (NPR).</p>
<p>But <a href="http://www.nature.com/nature/journal/v508/n7497/full/nature13151.html">looking more widely</a> reveals that even genes on the human Y with important functions (such as making sperm) are missing from the mouse Y, and vice versa.</p>
<p>Most spectacularly, species in two rodent groups have <a href="http://www.annualreviews.org/doi/abs/10.1146/annurev.genet.42.110807.091714?journalCode=genet">lost their entire Y chromosome</a>. Y genes have been either shunted to other chromosomes, or replaced – we don’t know by what. So it must be possible to dispense with the Y and start over again.</p>
<h2>A world without men?</h2>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/61638/original/yggrwz5j-1413263965.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/61638/original/yggrwz5j-1413263965.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/61638/original/yggrwz5j-1413263965.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=510&fit=crop&dpr=1 600w, https://images.theconversation.com/files/61638/original/yggrwz5j-1413263965.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=510&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/61638/original/yggrwz5j-1413263965.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=510&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/61638/original/yggrwz5j-1413263965.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=641&fit=crop&dpr=1 754w, https://images.theconversation.com/files/61638/original/yggrwz5j-1413263965.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=641&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/61638/original/yggrwz5j-1413263965.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=641&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Three species of whiptail: little striped whiptail, (_ Cnemidophorus inornatus_), New Mexico whiptail (<em>C. neomexicanus</em>) and western whiptail (<em>C. tigris</em>).</span>
<span class="attribution"><span class="source">Alistair J. Cullum/Wikimedia Commons</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>If the human Y disappears, will men disappear? If they do, that’ll be the end of the human race. We can’t become a female-only species (as have some lizards, such as the New Mexico whiptail) because there are at least 30 “imprinted” genes that are active only if they come <a href="http://www.ncbi.nlm.nih.gov/pubmed/16530039">through the sperm</a>. So we can’t reproduce without men.</p>
<p>So does that mean humans will become extinct in 4.5 million years? Not necessarily. The Y-less rodents have evolved a new sex determining gene, so why not humans?</p>
<p>Perhaps this has already happened in some small isolated population, where genetic accidents are much more likely to take hold. We wouldn’t know without screening chromosomes from every human population on the planet.</p>
<p>But a group of humans with new sex determining genes won’t easily breed with humans who retain the present XY system. Children of, say, an XX woman and a man with a novel sex gene, are likely to be intersex or at least infertile. Such a reproductive barrier can drive incipient species apart, as happened with <a href="http://www.nature.com/nature/journal/v415/n6875/full/415963a.html">Y-less rodents</a>. So if we return to Earth in 4.5 million years, we might find either no humans – or several different hominid species. </p>
<p>In any case, 4.5 million years is a long time. We have been human for less than 100,000 years. And I can think of several ways in which we are likely to become extinct long before we run out of Y chromosome.</p><img src="https://counter.theconversation.com/content/32893/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jenny Graves has received funding from the ARC and NHMRC and is a Fellow of the Australian Academy of Science.</span></em></p>The Y chromosome, that little chain of genes that determines the sex of humans, is not as tough as you might think. In fact, if we look at the Y chromosome over the course of our evolution we’ve seen it…Jenny Graves, Distinguished Professor of Genetics, La Trobe UniversityLicensed as Creative Commons – attribution, no derivatives.