Substack cometh, and lo it is good. (Pricing)

Open Thread – Late Feb.

I was busy. Then we lost power for days. So no updates on this blog. But a lot has happened while I’ve been trying to keep warm. Discuss. I have papers to read from what I can tell.

Follow me @razibkhan on Clubhouse. I have internet and plan on doing my usual 7 PM PDT event, this time on the genetics of Europe (and going to push through on the Substack post on Italy now).

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37 thoughts on “Open Thread – Late Feb.

  1. So I just found out about a paper through one of Narasimhan’s relatively old tweets. It was regarding Denisovan cranial and post-cranial genetic configuration. Just skimmed the paper’s figures, haven’t read it yet. Apparently they may have had narrower faces, broader heads and somewhat more gracile bodies than Neanderthals did. At least that much could be said about the specific Denisovan(s) that the DNA was taken from. Maybe the other divergent Denisovans whose DNA isn’t covered yet could be different.

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  2. I am really sorry about the cold and the blackout.

    I had saved the following for an open thread:

    “Did the Covid-19 virus really escape from a Wuhan lab?” by Matt Ridley and Alina Chan Published on: Sunday, 07 February, 2021

    “This is a more detailed version of the long article co-written with Alina Chan on the origin of the virus causing the covid pandemic which was published in the Telegraph on 6 February.”

    http://www.rationaloptimist.com/blog/did-covid-escape-from-a-lab/

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  3. Sorry to hear about your and your family’s hardships over the last days. Yep many papers about to read! Fast news days for ancient dna while you were offline

    https://www.nature.com/articles/d41586-021-00436-x“Million-year-old mammoth genomes shatter record for oldest ancient DNA”“This is the first evidence for ‘hybrid speciation’ from ancient DNA, says Orlando. “This is amazing.”

    Likewise: https://www.cell.com/current-biology/pdf/S0960-9822(21)00138-X.pdfThe oldest genome sequence from a non-permafrost environment… a 360,000-year-old cave bear. Very old dna, impressive.

    https://www.biorxiv.org/content/10.1101/2021.02.17.431573v1Inferring population histories for ancient genomes using genome-wide genealogies. Shotgun ancient dna.

    This identifies the “Europeans mutate differently” pattern (5’-TCC-3’→5’-TTC-3) identified in 2014, as one these authors believe linked to Anatolian Neolithic ancestry (which I think there was skepticism of in 2014, but they seem to believe high coverage whole-genome ancient dna support it). They suggest possibly a transitory genetic cause. I wonder if this would be some weird variant at the time which had a strong selective advantage in Anatolia Neolithic, but caused an odd mutational pattern. Or just drift. Also potential link to UV and melanoma to consider.

    Linked to previous 14 shotgun high coverage adna from – https://www.biorxiv.org/content/10.1101/2020.10.27.351692v1““A curated dataset of modern and ancient high-coverage shotgun human genomes””)

    Also: https://www.biorxiv.org/content/10.1101/2021.02.16.431497v1A unified genealogy of modern and ancient genomes.

    Linked I believe in part to release of https://reich.hms.harvard.edu/ancient-genome-diversity-projectPre-publication data release of high quality shotgun sequencing data from 216 ancient individuals

    Big labs appear interested in shotgun adna again after years of bigger capture sets; I guess coming to the idea that bigger capture sets is not providing better resolution on its own. (Possibly linked to whole-genome early farmer adna study from last year – The mixed genetic origin of the first farmers of Europe, Marchi et al).

    Saw you were already aware of most/all these on twitter, would be interested though to see what you and commentors think of any of this, and potential use for any of the datasets. It seems like Reich Lab’s new dataset is all from published capture samples, and doesn’t overlap at all with the high-coverage shotgun genomes from the past which are listed in “A curated dataset …” which includes lots of deep samples like Yana1, Ust Ishim, SunghirIII, KK1. The “Allen” new set includes numerous genomes from across the world (albeit with still a Europe and Middle Neolithic-Copper Age focus). Those may be co-analyseable with the previous high coverage shotgun samples published (the only difference I could see that could cause batch effects appears to be potentially damage control methods?). The Marchi paper also has some others. The press release for the Allen set talks about potentially integrating work from other labs in there. The highest coverage sample in Reich Lab’s set is a 35x coverage Orcardian Neolithic sample (matches with lots of Neolithic Irish samples previously published by Lara Cassidy and collaborators, such as “Incest King” NG10 and others).

    It seems like some further analyses should be possible on Yamnaya and Afanasievo genomes that Reich have at high coverage (and some really ar pretty high) using Site-Frequency Spectrum methods, as in the Marchi preprint? Maybe they can test more about formation of Steppe_EMBA population from high coverage KK1, high coverage Latvia_MN2 (EHG sample) which are already present in the other set from Cassidy/Pinhasi above. There are also high coverage Armenia_Chl and Armenia_EBA samples that could be used in that kind of analysis.

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  4. @Matt
    I have a question for you. What is the highest coverage individual from the Villabruna/WHG cluster that you are aware of?

    And if you have a list then could you possibly list the top 3 as well?

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  5. @DaThang, there is some subtlety on WHG that depends a little bit on whether we’re classing Iron Gates and alike samples as close enough (broadly Villabruna like), or we’re like “100% accept no substitutes, Italy Meso-like samples (who possibly expanded from a slightly separated Italian Refugium rather than a Balkan Refugium)”…

    But just looking at latest data files I have, there is at >8x coverage as minimum threshold –

    Allen Genome Diversity Project (shotgun): Serbia Iron Gates at: I4877 – 27.44x, I5236 – 26.9x, I4873 – 25.75x, I4878- 25.30x, I4914 – 24.85x, I5235- 23.55x, I5233 – 23.54x, I4916 – 14.73x, Latvia HG: I4596 – 23.35x, I4438 – 23.34x, I4432 – 21.41x, I4432 – 21.41x, I4916 – 14.73x, Hungary Koros HG: I1507 – 22.42x.

    “Curated Dataset of Modern and Ancient High-Coverage Shotgun Human Genomes”: Loschbour – 22x, Bichon – 8.44x.

    Cassidy 2020 (Dynastic paper) (shotgun): Ireland Mesolithic: SRA62 – 13.246x (in latest paper from above links).

    There’s a lot of MN and EN genomes with high coverage as well, so there is probably some scope to reconstruct WHG like genomes from the differences between them as well. The stated coverage seems to vary a bit from study to study (above is highest reported for each that I have to hand), but is generally high or low for same sample.

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  6. As usual, thank you for the data Matt. The Iron gates and Latvia HG all have EHG-like ancestry, and I couldn’t find the Koros sample you mentioned on global25, but the other Hungary_N HG had both little bits of EHG and Pinarbasi-like ancestries.

    Yeah I was looking for more so nearly pure WHGs so the closest to them in that list would be the Irish HG, the Loschbour HG and maybe Bichon (I couldn’t find his ID on the global25 list). I was wondering maybe if a complete WHG genome could be generated, without any or at least with minimal EHG traces and Pinarbasi traces, then perhaps a hypothetical (albeit regionally-mixed) WHG could be cloned. The ethics would be questionable since, it would most likely not be adapted to a post farming diet, but I thought about this hypothetical after looking at a recent comment on the Eurogenes blog which quoted someone who said WHGs would be indistinguishable from SSA in appearance. One way to find out and check for any lost alleles would be to test it directly!

    Of course, I guess the guy who was being quoted probably thought that people can’t tell the differences between faces from different places, but I ignored that point and went straight to the question about WHG skin colour in my thought (experiment?).

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  7. @Dathang: Interesting question; whether we’ve got or will ever have enough to clone a WHG person kind of beyond my scope. Whether from ancient DNA alone or supplemented with modern “salvage”. I’d think if so the ethical issues would be around whether we should bring a person into being to test hypotheses, more than issues like diet (which we solve the same way as for living people with same condition like Arctic natives; perhaps 3D printed steak for all) or low population size and high inbreeding coefficient (also true of very small group Native Americans, South Asian jatis etc).

    But does seem like if you’re able to clone a person, we’d also be able to just culture /generate the tissues (hair, skin, iris) directly, as a much quicker way and ethically clear cut way to tackle the problem. If Neanderthalized mini brains are possible, WHG mini skins might be. While for hard tissue, training neutral networks to reconstruct facial shape from skull shape, from living people, and incorporating such soft tissue info should be possible. So I don’t know if we’d need to clone a person to solve the question pretty decisively.

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  8. Diet is one of the easier things to take care of. But we don’t know what their social tendencies and other ways of experiencing the outside were. If it is incompatible enough it could result in a dangerous person.

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  9. Could be, although wouldn’t expect it to be too far outside of at worst what seen in Indigenous Arctic Circle, African, Australian ppl who were HG until recently. I think there would be a very high barrier to “Well, we can’t clone this person because they might be more violent than average”. But if it’s a big concern you just clone a female anyway to be on the safe side and mitigate most of it.

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  10. I’m fairly confident that if/when someone clones a Mesolithic human (or possibly even a neandertal) the popular media will blame their inability to integrate into modern society as due to whatever weird upbringing they had (raised in a lab?) or flaws in the cloning process if they are biologically inclined.

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  11. I listed danger as without giving details. They could end up gravitating towards more sophisticated and more dangerous acts of sabotage than one man violence. Why? Maybe they end up not understanding or in some ways better understanding the higher structure of civilization and since they aren’t selected to ‘work’ for it, things could get messy in an extreme case.

    Though even in a more mundane case, people like Australian aboriginals seem to be quite miserable in their interaction with modernity because of all of the health problems.

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  12. Oh yeah, well, I guess if there was a WHG clone he or she could be a Zed from Zardos meets Johann Liebert type (a sort of superhuman barbarian manipulator to bring down civilization); it’s possible… But yeah to harp on the same again, I wouldn’t say it’s too likely – most people from groups who were HG until recently weren’t (Siberian natives, Bushmen, Hadza, Mbuti, Australians, Native Americans from Pacific NW). Purely hypothetically if such a thing happened.

    On another topic was thinking about “Using Y-chromosome capture enrichment to resolve haplogroup H2 shows new evidence for a two-Path Neolithic expansion to Western Europe” preprint from this week, (https://www.biorxiv.org/content/10.1101/2021.02.19.431761v1), which is about unbiased high coverage NRY ancient DNA to find Y sequence variation lost in capture (because of ascertainment) and low coverage shotgun (because low coverage of haplogroup defining SNPs, and mostly just monomorphic sites).

    A previous paper by Kivisild in 2017 talked about these drawbacks – https://link.springer.com/article/10.1007/s00439-017-1773-z. One point it made in a figure was that some samples like German Corded Ware at a site presented pretty basal R1a, post dating star expansion but otherwise not recently related with each other in recent generations. But of course, maybe this apparent effect might have been due to lost clades or bias in capture array.

    It seems like it could be worth reanalysing some of these sets of LNBA capture samples with this approach; finding lost clades and a more accurate account of mutations accumulated over time would allow a better resolution of A) how much recent patrilineal clustering really existed in the LN-EBA and B) dating time elapsed since star-like divergence more accurately. These are interesting because there’s some conjecture about whether or how much LN-EBA CWC / BBC were organised around patrilineal clans and whether this drove expansions. A firmer idea of whether they were actually patrilineally related in, like, within 10 generations, might help to explain those dynamics.

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  13. I was thinking more so along the lines of Kuze and his mind-body disconnect, and the eventual lack thereof fueling whatever he does later on in 2nd gig.

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  14. “But if it’s a big concern you just clone a female anyway to be on the safe side and mitigate most of it.” – Evidently you haven’t met too many Australian Aboriginal women from outside of the major cities. “Handle with care” would be my advice.

    “Australian aboriginals seem to be quite miserable in their interaction with modernity because of all of the health problems.” That is because you don’t see or hear about all of the Aboriginal people living quietly successful lives in the suburbs. But with minimal effort, you could observe those well paid Aboriginal people engaged in elite level sports, or read about those graduating in medicine and dentistry, or working as park rangers, or working for the military as coast watchers along the northern coastline, so it’s not really a forgivable comment.

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  15. @sandgroper

    The comment is perfectly accurate. Apart from sports there are zero examples of people with majority Aboriginal ancestry being successful in modern professions (although a few hold such roles due to affirmative action or government sinecure).

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  16. Perfectly accurate, is it, when you have just acknowledged examples of where it is not true (elite sports people, most of whom look pretty healthy to me and not remotely miserable)? Zero, eh? It’s a big call to claim to know about every single Aboriginal person in Australia, which you obviously can’t. To add to the examples I have already given, what about running cattle stations or working in mining?

    I have worked with Aboriginal guys in engineering, so I know for a certainty that you are either a liar or a moron, or both.

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  17. @Sangroper

    That part of my comment was regarding the health of Australian aboriginals since that point was speculating other issues a mesolithic human may have in post-neolithic civilization. I didn’t say all are one way or the other but the statistics about the average health and disease frequencies vary between Aboriginals and non-Aboriginals are clear.

    https://www.aihw.gov.au/reports/indigenous-australians/indigenous-health-welfare-2015/contents/health-and-disability-key-points

    Diseases like CVD and diabetes are more common, and this has something to do with the lack of neolithic agricultural adaptation in a large scale. The neolithic when it swept western Asia and Europe must have brought a wave of maladies with it. People heavily depending on the types of foods that they only rarely consumed in the past with metabolisms that aren’t used to this stuff would have suffered en masse.

    Not only that but there was some paper on increasing resistance to communicable diseases in the neolithic. They would have died not just of diet based diseases but also because of communicable ones that would have relatively speaking, exploded due to sedentary large population sizes.

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  18. Aboriginal health is not a simple issue, due to (i) the legal definition of who qualifies as Aboriginal (which is not genetically based), and (ii) the large population of Aboriginal people who live in appalling living and sanitary conditions in remote settlements with little or no access to modern health care, lack of employment,and with a lot of issues with alcohol, tobacco, drugs, sniffing glue, solvents and petroleum products, etc. And with lack of availability of fresh vegetables and generally very poor diet high in refined carbohydrates. Those who do best are those who revert to traditional lifestyle and live off the land, so to speak – hunting, fishing and gathering native plant foods, and stay away from the whole suite of white vices. But then it is hard to earn a living that way, which is why a lot of them work as cattle herders (stockmen – the Australian word for cowboys; they take to riding horses like ducks to water), park rangers and coast watchers.

    The real points in what you are saying are:

    1. Obviously a high proportion of the Aboriginal population of Australia died of communicable diseases like smallpox, measles, influenza and tuberculosis with the arrival of white settlers (there are no numbers, but anecdotally they were hit very badly by the ‘Spanish Flu’ when it finally got into Australia), and even now some people with a high % of Aboriginal ancestry appear more susceptible to some infectious diseases like tuberculosis and syphilis (syphilis! in the 21st Century!) (but it is hard to know what proportion because of the above-mentioned legal definition, environmental factors and lack of access to health care – the government is trying to keep people out of the Aboriginal lands and remote settlements because they appear to be particularly susceptible to dying from Covid-19. Fortunately, at least for the time being, Australia has been largely successful in eliminating it from the country.) This was exacerbated by disruption of their traditional nomadic hunting/gathering routes by fencing, making them dependent on food hand-outs from whites, who fed them all the good stuff like white flour, biscuits, sugar and jam, which they obviously loved, and armed conflicts with white settlers when they killed livestock to live on, not understanding the legal principle of personal ownership.

    2. People with a high proportion of Aboriginal ancestry generally do particularly badly on a modern western diet, suffering disproportionately from obesity, hypertension, Type 2 diabetes and the other ‘metabolic’ health conditions (even much worse than whites – Australia is now an obese country). The smart ones (and there are plenty of them who do get this point) understand this and put themselves on something much closer to their traditional diet, and engage in efforts to teach this to those who haven’t figured out that a diet high in sugars, other refined carbohydrates and alcohol will kill them. Australian culture generally, such as it is, is built on alcohol, and it does them no good at all, in more ways than one. It doesn’t do anyone else much good either, but they are particularly susceptible.

    I didn’t mean to write a book. I just didn’t like the way you put it, because there are plenty of Aboriginal people who do understand that genetically they are in effect ‘pre-Neolithic’ people and order their lives accordingly, and they do OK, provided they have as much access to modern health care as everyone else. Generalisations can be odious, and I have ancestral reasons for taking exception, if you get my meaning. It is highly likely that if the definition of Aboriginal was confined to people with a high % of Aboriginal ancestry, then on the mean their health outcomes and life expectancy would be even worse than shown by the official data, but we can’t know. Those problems are not insurmountable, though, just like obesity is not, or should not be, an insurmountable problem in the USA, UK and Australia.

    One final point – the data you linked to include Torres Strait Islanders, who are different people. Lumping them together with Aboriginal people as one group of ‘indigenous’ just serves to further obfuscate the particular problems and issues. This is one reason why a lot of Aboriginal people actually object to being referred to as ‘indigenous’ and insist on being called Aboriginal.

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  19. I don’t want to mislead you, the part of the comment was mentioned simple to show that there are things that would differentiate the hypothetical modern WHG from most other people alive today, even mundane things like diet would have an influence. An influence which would ‘other’ them so to speak, which in turn could push them in directions that most people don’t go into. And if the neolithic also brought about a new bicameral mindset, then the mesolithic individual may be able to see society in a way not seen by most or maybe even all people alive today. Even though Australian aboriginals are not heavily adapted to communicable diseases, they still have a neolithic spread, which would have spread a neolithic culture kit and mindset. So in the extreme case scenario, a WHG could be societally further removed from the main population than even recently transitional populations. I usually don’t go down such tangents, but it was interesting to see where an isolated WHG in the modern day or an even older pre-mesolithic individual (probably north Eurasian since that is where most pre-mesolithic salvageable DNA is located) could head in modern society.

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  20. Now I am interested, enough to want to explore further. What do you mean by “neolithic spread” here?

    What do you have in mind with “neolithic culture kit and mindset”?

    I guess you probably know, but if not I will tell you, although you dare not speak this openly – ‘real’ Aboriginal people (I mean people of 100% Aboriginal ancestry) have different brain structure to other populations.

    Also, they have some differences in cognitive ability (e.g. enhanced spatial memory and directional sense) and, in the absence of eye disease (trachoma), much greater visual acuity than other populations. Greg Cochran told me that Central Asians also have enhanced visual acuity, but not nearly as much as Aboriginal people.

    Infamously (and you dare not speak this openly either) they have mean IQ of 65 – going by that, they should all be drooling idiots who can’t take care of themselves, but that is very obviously not the case.

    As for whether their bicameral minds are any different from other people’s bicameral minds, that’s a tough one – how could you tell? Having known quite a lot of real Aboriginal people, is there a way I could know this?

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  21. I wasn’t talking about intelligence. I meant since Australian societies were in the neolithic phase at European contact, they would have had a neolithic culture set. This includes the neolithic mindset (if the neolithic is associated with one that is). I am reaching but if the neolithic mindset distinction is true then Aboriginals would have already been bicameralized before European arrival. Bicameralization of the mind is an idea put forth by Julian Jaynes. According to this: the human mind until the end of the bronze age was structured into two parts one that spoke and one that listened. This could have originated around the neolithic and so if the neolithic really is distinctly associated with a mindset than this would be one candidate. Even though it is mostly a thing of the past, people today still retain certain aspects of this thinking. A mesolithic or pre mesolithic would not have had that bicameral mindset in the first place. I am kind of combining ideas of Jaynes and his responders here. So such a person, if all of this is true, would have a different thought process than the majority of people alive today in any post mesolithic community

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  22. “Australian societies were in the neolithic phase at European contact” – What? No they weren’t. Wherever did you get that idea?

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  23. DaThang: I will have to watch that to really get the reference 😉

    I always assumed that for Jaynes mechanism of proposed change (whatever we think of it), it had to be a “software install”. It’s very difficult for me to see how a hardware change could work selectively; if a single mutation then we’d see a cognitive mutation with a huge signal of selection that spread like wildfire with a huge selective coefficient (going from 0 at Iron Age Greece to ubiquity by the Christian Era is a serious coefficient); if polygenic, then the same / similar genetically independent polygenic sweep across many groups mediated by sometimes fairly slight cultural contact and with very different social structure (inc. groups as isolated as Native Americans?)…

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  24. DaThing,

    Neolithic is commonly understood to be a lack of metalworking + agriculture. Papuans (and Polynesians, for that matter) were Neolithic peoples. Aboriginal Australians would be classified as technologically (and culturally) Mesolithic.

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  25. @Sandgroper

    https://en.wikipedia.org/wiki/Prehistory_of_Australia#Changes_c._4000_years_ago

    There was a change in domestication, languages and stone tool usage around 4,000 years ago. Usually neolithic = farming, but it is possible to have a neolithic without farming.

    @Matt
    This is a very hypothetical territory so I am going with a lot of intuition here. The idea is that this change began with the neolithic and was fundamental in the neolithisized populations. It was retained until the end of the bronze age. After this, the social technology used to make use of the system broke down. I didn’t say that there was a massive shift in selection at the end of the bronze age. The system that was in use from neolithic to bronze ages was retained, but because the social structure using it broke down, people would have mostly reverted to non-bicameralism but not entirely. The system that was selected for is still there, so people still retain some bicameral type of activities. The difference with a WHG would be that it wouldn’t have any bicameral-like traits since it didn’t have the hardware selection (neolithisization) installed in the first place.

    This thought isn’t revolutionary, most people would agree that more independent and violent types would be selected against, I extended that to inherent social conditioning and selection of traits which would make it easy.

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  26. I can quote Wikipedia too: “Australia, in contrast to New Guinea, has generally been held not to have had a Neolithic period, with a hunter-gatherer lifestyle continuing until the arrival of Europeans. This view can be challenged in terms of the definition of agriculture, but “Neolithic” remains a rarely used and not very useful concept in discussing Australian prehistory.”

    They didn’t domesticate anything, they were given the dingo by Austronesian traders visiting the northern coastline. Some guy invented the stone tool equivalent of the Swiss Army Knife, which is very helpful to nomadic people who can’t carry much, so everyone copied it. You can read about how Puma-Yungan languages spread around the country. Keith Windschuttle is a raving racist crackpot.

    There was no Neolithic in Australia, unless you want to invent a completely new and meaningless definition of Neolithic, which seems possible.

    I am no longer interested.

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  27. If you really want a population to study that I presume you can be persuaded were pre-Neolithic, you can consider Tasmanian Aboriginal people. They are only recently extinct, there were ample exchanges between them and Europeans which were documented in considerable detail, and Tasmania was separated from the Australian mainland long before any of the changes that occurred around 4,000 years ago.

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  28. @Karl, unless we’re Russian in which case Neolithic is pottery and other new stone and ceramic tools. Which to be honest does perhaps make more sense in the otherwise materials centered system. “Iron, bronze, copper, agriculture(?), stone” follows less logically than: “Iron, bronze, copper, new stone+ceramic, old stone” (for all that the materials centered perspective is right or wrong!).

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  29. @karl

    For example, there were hunter gatherers using neolithic elements in parts of northern Europe like the swifterbant.

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  30. Admittedly, the Mesolithic-Neolithic transition was a weird one. Plenty of groups of people invented metallurgy prior to agriculture, including the Inuit (who worked meteoric and telluric iron) and native Americans around the Great Lakes (who worked copper). It was just that the materials were cold-worked and not actively smelted. We also classically interpret pottery as being a post-Neolithic invention, because that’s what happened in the Near East and Europe, but in East Asia, Sub-Saharan Africa, and the Americas pottery came long before agriculture.

    While Aboriginal Australians didn’t domesticate anything, they were moving towards active land-management with their use of fire. And the Gunditjmara apparently actively engaged in aquaculture of eels, to the point of building dams and canals to create additional wetland environments. Certainly not proto-agriculture, but arguably they were on their way to being a socially complex hunter-gather society like the Northwest Coast of North America.

    Of course, if you want to include the Torres Strait islanders, there was some agriculture taking place in Australia. Though they are culturally, linguistically, and genetically speaking Papuan. I seem to remember Jared Diamond had a whole explanation of why agriculture didn’t spread across the Torres Strait into Australia, but in retrospect it seems a lot less persuasive, now that we know that people of Papuan genetic origin spread from Timor to Fiji.

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  31. Kind of interesting – https://medicalxpress.com/news/2021-02-genes-obesity-disease.htmlGenes identified that increase the risk of obesity but also protect against disease

    a team of researchers—led by scientists at the University of Copenhagen and Icahn School of Medicine at Mount Sinai, New York—have identified a range of genes that are linked to both elevated levels of body fat, as well as offering protection from some of the negative health impacts of obesity.

    “We used a data-driven approach in this study, which led us to find new genes associated with fat tissue health, instead of the known obesity genes associated with central nervous system, which control satiety and are typically linked to unhealthy obesity,” says Lam Opal Huang.

    Obesity generally very bad, but sorting out which genes relate to higher fat tissue accumulation rather than… disordered appetite / eating (if I’m following?) finds a more mixed picture (where fat accomulation genetic variants are not necessarily bad). Doing annotation for function gives more informative picture about variants? And get from there to more effective medical plans and treatments.

    Interesting that one of the genes identified is our old friend ALDH2. I hadn’t heard of this link before, but this is apparently not a new association – https://pubmed.ncbi.nlm.nih.gov/31368102/ and https://www.frontiersin.org/articles/10.3389/fgene.2020.575049/full.

    Judging by this study it seems like it’s the ancestral variant (G) rather than derived (A) variants (common in East Asians, SE Europe/West Asia) that is associated with obesity… But may not necessarily be associated with metabolically unhealthy obesity, if I am inferring on this latest study correctly.

    Maybe some of the very strong selection for ALDH2 variant in East Asia (which is really looking like strong selection in North China in the last 2000 years https://www.biorxiv.org/content/10.1101/2020.11.17.387761v1.full !) is actually related to changes in selection for fat mass somehow (or maybe rather this explains why derived ALDH2 was not selected for in other populations, because the ancestral variant has some protective effect).

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  32. @DaThang, thought this might be one for you to be interested in, in relation to both your questions above about about a week ago, early in the comment thread.

    I think above you note an interest in I think the Gokhman 2019 paper which was about predicting Neanderthal and Denisovan anatomy from methylation maps and identifying differences. (That’s the one Vagheesh Narasimhan mentioned on twitter.)

    Well, there was another paper from same author in March 2020, which I think I missed (and probably some others) because of Covid19 news . This is – https://www.nature.com/articles/s41467-020-15020-6“Differential DNA methylation of vocal and facial anatomy genes in modern humans”, Published: 04 March 2020. This builds on the earlier work.

    Also of relevance to your previous question on WHG genomes – “We also sequenced to high-coverage and reconstructed the methylomes of the La Braña 1 individual from Spain (~8 kya, 22×) (which was previously sequenced to low-coverage) and an individual from Barçın Höyük, Western Anatolia, Turkey (I1583, ~8.5 kya, 24×), which was previously sequenced using a capture array”. I noticed that the I1583 is included in the Allen Ancient Dna set, which what led me to Gokhman’s 2020 paper, but the high coverage La Brana is not, yet. This may end up being forthcoming in a future version of the dataset, but I think would be the highest coverage WHG proper or equal with Loschbour if so.

    This was because they were trying to extend the comparisons to really lens the methylation changes in Denisovan and Neanderthal dna tightly.

    They look at in particular in a gene NFIX, in relation to the AMH specific pattern of reduced facial size, and which is implicated in Marshall Smith / Malan Syndrome, cranial disorders that present a phenotype that is in some respects opposite to the archaic human configuration.

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