Sex and the CTAG: What Ancient DNA Tells Us About Our Ancestors' Liaisons

Ancient DNA Sex and the CTAG: what ancient DNA tells us about

our ancestors’ liaisons Downloaded from http://portlandpress.com/biochemist/article-pdf/42/1/24/867108/bio042010024.pdf by guest on 26 September 2021

Christiana Scheib The development of next-generation sequencing (NGS), a technology coincidentally well-suited to (University of Tartu, Estonia) highly fragmented, low copy number DNA sources, spawned a rapid expansion in the field of ancient DNA (aDNA). It has gathered a reputation as a sexy subject, quite literally. Some of the headlines targeted to the public: ‘Mystery humans spiced up ancients’ sex lives’ in Nature News or ‘Viking sex tourists lived happily ever after with Britons’ from The Independent, would make any scientist blush and probably want to bang their head against a brick wall. As problematic as these headlines are, people keep writing them because sex sells and while aDNA might not tell us exactly what our ancestors were into, it has and will continue to provide other unique insights regarding our reproductive past.

What aDNA can tell us about actual found today in high percentages (~6%) in Australasian ancient sex and Oceanic populations and specific genes from this ancestral population have conferred an adaptive The bread and butter of the aDNA world is the human advantage to high altitude in Tibetan people today. Not migration and admixture story. In 2010, the first draft only have humans had conjugal relations with their genome of a Neanderthal was published and with it the archaic hominin partners, but the Neanderthals and first concrete evidence that as anatomically modern Denisovans themselves had offspring when they met, humans left Africa, they met and had children with their as evidenced by one incredible find from the same cave. Neanderthal cousins already inhabiting wide swaths of From a single fragment of loose bone, identified through Reconstruction of Mesolithic Eurasia. The genome of another sister species from a its uniquely hominin protein structure, researchers at life at the Selva di Cadore cave in the Altai Mountains, the Denisovans, led to the the Max Planck Institute in Leipzig extracted aDNA Geological Museum, Italy. re-discovery that when humans meet each other, they and discovered that the bone belonged to the child of a © Shutterstock have sex. Fragments of this archaic hominin’s genome are Neanderthal mother and Denisovan father.

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In more recent history, aDNA studies on all continents First, it is important to understand how we get aDNA and time periods have shown that at any given point, from deceased humans. It can be sourced from any dierent populations of people have met and then have biological remains including skeletons and mummies; had sex with each other, producing the populations however, skeletons are the primary target for aDNA in those areas today. For example: in Europe, hunter- studies due to the wider availability and being less gatherer populations (whose ancestors had sex with chemically complicated than mummies. e inorganic Neanderthals), had sex with incoming Neolithic farmers matrix of bone is like a sponge for proteins and DNA, from Anatolia and their ospring then later had sex with adsorbing whatever is near at the time of death. Most the people coming in from the Eurasian Steppe. Today’s studies interested only in the human genome target reality of mass migration into Europe and melting- the pars petrosa, or the inner ear canal as this bone is pot culture is nothing new and if aDNA has taught very dense, full of osteocytes (bone cells) and tends to us anything, it is that the sharing of genes and culture preserve well, leading to high human DNA content. Downloaded from http://portlandpress.com/biochemist/article-pdf/42/1/24/867108/bio042010024.pdf by guest on 26 September 2021 between previously separated populations is the norm Teeth are also quite dense and thanks to the blood in the (and will likely benet our descendants too). pulp chamber, provide a diverse source of human and microbial DNA. Dental calculus, a calcied biolm that Swipe left, swipe right forms on unbrushed teeth, is particularly prevalent in ancient mouths as they did not have access to modern Sexual selection is a key component of evolution and dental care and provides a rich data source for mining modern studies indicate that visual and non-visual cues the oral microbiome. Enterprising researchers have used (e.g., pheromones) aect our mate choice. What made aDNA to unravel the mysteries of ancient non-STIs like cross-species coupling so attractive? Well, we don’t really plague (Yersinia pestis), Salmonella enterica and Hansen’s know as, a er all, beauty is in the eye of the beholder. disease or leprosy (Mycobacterium leprae), and some STIs Neanderthals have been physically reconstructed from like syphilis (Treponema pallidum) and hepatitis B (HBV). skeletons using forensic techniques, but what about the Due to their structure, treponemal diseases and Denisovans, where we have only a genome? Researchers viruses tend to degrade more easily than thick-walled have used ancient bone epigenetic information to attempt bacteria and are dicult to detect molecularly, especially a reconstruction and ancient protein identication will when copy numbers are low in comparison to the host eventually reveal the Denisovan skeletons hiding in genome. However, a few rare genomes from 17–19th our museum collections. As for the non-visual aspect century congenital syphilis cases have been sequenced, of attraction, it has been shown that humans tend to showing that dierent strains led to similar physiological choose partners with innate immunity genes as dierent conditions. A number of HBV genomes from across as possible from their own, which confers an advantage Eurasia (up to 7000 years old) show high diversity to their children. is phenomenon could very well have of strains in the past, a high correlation with human been at play in the past because some of the genes we migration and a history of recombination. e process have inherited from Neanderthals that have not been of recombination occurs when a host is infected with purged by purifying selection, have helped our immune multiple strains, or as a journalist might sensationalize: systems. is is a double-edged sword though as nature ‘multiple sex partners contributed to mutant virus’. In does not develop an immune response without an all seriousness, it’s not clear how that recombination infectious trigger. event occurred. HBV can be transmitted via any infected bodily uid and for all we know, our ancestors had some If you touch each other, blood-drinking rituals or were sharing tattoo needles. you will get chlamydia... and die e point is that, as we saw in the previous section, throughout history groups of people have come into For anyone who was forced to sit through a sexual contact with each other and not only shared their genes, education class taught by the reluctant school football but also their diseases. coach, the above quote from the 2004 lm Mean Girls With this in mind, we should expect that not only do really hit home. Of course, it’s exaggerated for the joke Neanderthal genes live on in our genomes, but their STIs and in today’s world, even if you do get chlamydia or should still be in circulation as well. A recent paper noted any other bacterial sexually transmitted infection (STI), that the pattern of variation in human papillomavirus you most likely will not die because it can be treated (HPV) might indicate host transfer from Neanderthals with antibiotics (for now). However, for most of human to modern humans. is hypothesis is hard to pin down history, this was not the case and even today viral however, because the high mutation and recombination infections prove more dicult and can have lifelong rate in these organisms means that a lot of information complications. So, what has aDNA shown us about gets erased and is impossible to see in modern genomes. ancient sexual health? is is where aDNA could step in to save the day. e

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Denisova Cave (Siberia, classics, chlamydia and gonorrhoea unfortunately may better than DNA fragments and could be present even Russian Federation). never be recovered from ancient remains because they when DNA is not detectable. Unique peptides, such as Discoveries from this cave infect so tissues that are not in direct association with those found in the HSV1 viral capsid or HBV external have completely changed bones; however, if an oral infection was present there is core antigens could be used to detect pathogens and in our view on archaic hope that it could be found in teeth. One STI that we the latter case even identify the subtype in the absence hominin interactions. should nd in teeth is herpes simplex virus 1 (HSV1), of the high DNA coverage needed to determine strains. © Shutterstock which infects over 60% of the global adult population ese ancient proteins could even do more than help and HSV2 anywhere between 10 and 25% (and can infect determine infections, they might help us identify the the oral cavity in some cases). Considering the fact that other potential side eect of sex: pregnancy. teeth are a popular target for aDNA studies, HSV1 lies latent in the trigeminal ganglia and has been recovered Don’t have sex, because you will from dental plaque and teeth in studies of periodontal get pregnant and die disease, one would think that nearly every skeleton should have some HSV1 DNA waiting to be discovered. Ancient proteomics could expand our understanding of Looking at the current aDNA pathogen literature, this historical circumstances in pregnancy and the mortality does not seem to be the case. Why? Perhaps because surrounding it. Until very recently, humans did not HSV1 tends to stay latent most of our lives and would have the benets of advanced surgical knowledge, blood only lead to high viremic levels in rare circumstances or transfusions or antibiotics. us, we would expect there maybe our current methods and sample sources are not to be a much higher number of women who died during ideal for detection. and around childbirth than today and at least some of the For this reason, our lab is trying additional bio- skeletons we are analysing should fall into this category. molecular techniques to beef up detection rates. Fetal bones do not preserve well and can be missed Proteins, with more complex structures, tend to preserve during excavation leading to an under-representation in

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the archaeological record. ere is no way to tell just by Christiana Scheib is the head of the aDNA looking at a female skeleton whether she was pregnant, research laboratory at the Institute of but many proteins are produced in association with Genomics, University of Tartu, Tartu, pregnancy including human chorionic gonadotropin, Estonia. Her early research as a PhD which is not produced in other physiological states student at the University of Cambridge (except testicular cancer, but here I think it is easy to optimized protocols and explored distinguish between this and pregnancy). As the eld the complex genetic history of Native expands to include new wet lab techniques and our American populations. Always fascinated by disease, her online reference databases continue to grow, we can postdoc focused on retrieving and analysing pathogen DNA expect to learn a lot more about our sexual history. ■ from medieval skeletons. Her current focus is on integrating DNA and proteomics methods for the identication and analysis Downloaded from http://portlandpress.com/biochemist/article-pdf/42/1/24/867108/bio042010024.pdf by guest on 26 September 2021 Summary of ancient pathogens to gain a better understanding of host– pathogen dynamics and how they have aected our genomes We will never know whether Neanderthal women today. Email: [email protected] gossiped with their girlfriends a er an encounter with an anatomically modern human, but we do know that certain genes have been preferentially conserved in modern genomes, some with obvious adaptive benets and it appears that the Neanderthal male–Homo sapiens female pairings were more evolutionarily successful than the other way around. We know that they gave us their diseases, but also their immunity genes. e recovery and analysis of aDNA and proteins has revealed two underlying truths about human nature: 1) wherever and whenever humans meet, they will hook up and 2) humans love talking about it.