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Thread: Limits of selection against Neanderthal introgression

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    Limits of selection against Neanderthal introgression

    See:

    Martin Petr, Svante Pääbo, Janet Kelso*, Benjamin Vernot*

    "The limits of long-term selection against Neandertal introgression"

    https://www.biorxiv.org/content/bior...62566.full.pdf

    "Several studies have suggested that introgressed Neandertal DNA was subjected tonegative selection in modern humans due to deleterious alleles that had accumulated inthe Neandertals after they split from the modern human lineage. A striking observation insupport of this is an apparent monotonic decline in Neandertal ancestry observed inmodern humans in Europe over the past 45 thousand years. Here we show that thisapparent decline is an artifact caused by gene flow between West Eurasians andAfricans, which is not taken into account by statistics previously used to estimateNeandertal ancestry. When applying a more robust statistic that takes advantage of twohigh-coverage Neandertal genomes, we find no evidence for a change in Neandertalancestry in Western Europe over the past 45 thousand years. We use whole-genomesimulations of selection and introgression to investigate a wide range of modelparameters, and find that negative selection is not expected to cause a significant longtermdecline in genome-wide Neandertal ancestry. Nevertheless, these modelsrecapitulate previously observed signals of selection against Neandertal alleles, inparticular a depletion of Neandertal ancestry in conserved genomic regions that are likelyto be of functional importance. Thus, we find that negative selection against Neandertalancestry has not played as strong a role in recent human evolution as had previouslybeen assumed."

    The functionally important deleterious genes were wiped out pretty quickly it seems, and it appears that very little continuing selection has gone on.

    Interesting that according to the authors it's gene flow from West Eurasians into Africans which complicated the mathematics, not the reverse.

    Also, Basal Eurasians, contrary to assertions by other scholars previously, have, according to them, the same amount of Neanderthal ancestry as any other Eurasians, i.e. about 2.5%

    So, the initial admixture with Neanderthals could indeed have taken place in the Middle East, and the location of the Basal Eurasians wouldn't be a problem. They could have been located there as well.


    LeBrok was always skeptical that selection against such "weak" deleterious genes continued past the first stage of admixture. If other papers don't suggest this is an incorrect analysis, it seems he was right.

    Didn't Dienekes at one point say something like this, i.e. that gene flow between Africa and Eurasia might lead to misconceptions or problems with the analysis?
    Last edited by Angela; 05-07-18 at 22:55.


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    Razib Khan has posted his thoughts on the paper and its implications.
    https://www.gnxp.com/WordPress/2018/...medium=twitter

    "The basic argument in the preprint is that the model assumed for the ancestry of West Eurasians and Africans was wrong. Wrong assumptions can lead to wrong inferences. Using two Neanderthal genomes which are from different populations, one of whom directly contributed to the Neanderthal ancestry in modern humans, a new statistic which was insensitive to model assumptions about modern human phylogeny was computed.
    The older statistic held that West Eurasians and Africans were distinct clades which had not had gene flow in ~50,000 years. Using simulations the authors argue that the best fit to the statistics that they do see, the earlier flawed one, and the current more robust one, is a situation where a population of West Eurasian origin mixed with Africans starting about ~20,000 years ago."

    "
    As for the other explanation, that Neanderthal-less Basal Eurasian ancestry diluted the European hunter-gatherer fractions, the authors seem very skeptical of that. One point the authors make is that though an early European farmer was estimated to have ~40% Basal Eurasian, its Neanderthal estimate is still quite high. Iosif Lazaridis points out that this is an old estimate, and the Reich group now puts it closer to ~25%. Additionally, another recent preprint put the fraction closer to ~10%. With such low values, it is possible that Basal Eurasians may have had low Neanderthal fractions, but that that was a marginal effect on the aggregate West Eurasian ancestry quantum from Neanderthals."


    In other words, the authors may have placed too much emphasis on the presence of modern levels of Neanderthal in Stuttgart versus 44% Basal Eurasian, and Basal Eurasians may indeed have had less than other West Eurasians, but it wasn't the main factor.

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    From Iosif Lazaridis via twitter:

    "

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    West Eurasian admixture to Africans !!! yes I knew it !!



    Just by looking at pairwise Fst tables like these, Africans have less distance to all West Eurasians compared to East Eurasians, this has implications on the debate about the origin of haplogroup E, since it can appear in Epipalaeolithic Levantines without African admixture.

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    Iosif Lazaridis‏ @iosif_lazaridis 18h18 hours agoMore
    Or D(Eastern non-African, West Eurasian; African1, African2)if African1 is affected by admixture from West Eurasian more than African2 (hard to imagine all Africans being affected the same within 20ka) these should be negative.
    I can answer this, if the test was done on modern West, Central, and East Africans, and they all have affinity to West Eurasians, then only geneflow to the ancestors of first Bantu farmers and other West Africans is necessary, because they colonized all Africa later.

    Probably the same wave that brought Iberomaurusians, maybe a related group ventured further south ?

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    ^ good point here
    "What I've seen so far after my entire career chasing Indoeuropeans is that our solutions look tissue thin and our problems still look monumental" J.P.Mallory

    "The ultimate homeland of the group [PIE] that also spread Anatolian languages is less clear." D. Reich

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    Quote Originally Posted by IronSide View Post
    I can answer this, if the test was done on modern West, Central, and East Africans, and they all have affinity to West Eurasians, then only geneflow to the ancestors of first Bantu farmers and other West Africans is necessary, because they colonized all Africa later.

    Probably the same wave that brought Iberomaurusians, maybe a related group ventured further south ?
    Perhaps. That's the speculation of the Mota papear.

    There's documented gene flow to East Africa.

    Central and West Africa are a bit more problematic.

    I don't know where this leaves these papers.

    The first one found West Eurasian all over Africa: (Mota paper)
    https://www.nature.com/news/first-an...ration-1.18531

    "Co-author Marcos Gallego Llorente, an evolutionary geneticist at the University of Cambridge, UK, suggests that Middle Eastern farmers later moved south to Africa, bringing new crops to the continent such as wheat, barley and lentils. The team also found vestiges of these migrants’ DNA in people all across sub-Saharan Africa — probably carried by later migrations, such as the expansion of Bantu-speaking groups from West Africa to other parts of the continent around 1,000 years ago."


    Then, the authors retracted that claim, limiting it to East Africa.
    https://www.nature.com/news/error-fo...genome-1.19258

    "Andrea Manica, a population geneticist at the University of Cambridge, UK, who co-led the study, says the team made a mistake in its conclusion that the backflow reached western and central Africa. “The movement 3,000 years ago, or thereabouts, was limited to eastern Africa,” he says.Incompatible software

    Manica says that the error occurred when his team compared genetic variants in the ancient Ethiopian man with those in the reference human genome. Incompatibility between the two software packages used caused some variants that the Ethiopian man shared with Europeans (whose DNA forms a large chunk of the human reference sequence) to be removed from the analysis. This made Mota man seem less closely related to modern European populations than he actually was — and in turn made contemporary African populations appear more closely related to Europeans. The researchers did have a script that they could have run to harmonize the two software packages, says Manica, but someone forgot to run it.

    Pontus Skoglund, a population geneticist at Harvard Medical School in Boston, Massachusetts, says that he was surprised by the claim that as much as 6–7% of the ancestry of West and Central African groups came from the Eurasian migrants. But after obtaining the Mota man’s genome from Manica’s team, he and his colleague David Reich carried out their own comparison and found no evidence for that conclusion. They informed Manica’s team, who then discovered the processing error."

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    This may also be related to problems of conflicting levels of sub-Saharan African ancestry in modern or ancient populations in the Near East.

    examples:

    1- in the ancient Egyptian paper, modeling modern and Ancient Egyptians used a "West Eurasian" source from a set of (French, Anatolia_N, WHG, EHG, SHG, Iran_N, CHG, MA1) to compute SSA ancestry, populations with more Basal Eurasian reduced African ancestry, especially Iran_Neolithic, reduced Ancient Egyptian SSA to 3% and modern levels to 10%, while using WHG and other hunter-gatherers needed 10% african ancestry in Ancients, and 17% in moderns.

    This shouldn't alter SSA levels if ancient farmers didn't have afrcian ancestry, we know they didn't from Lazaridis(2016), formal stats showed no differecne in SSA levels between Natufians and WHG/EHG, which means it's most likely null.

    https://media.nature.com/original/na...ms15694-s6.pdf

    2- in the same paper, ADMIXTURE used a component centered on Natufians, modeling Arabian popualtions like Saudi, Yemeni Jews and BedouinB, almost completely removed SSA ancestry.

    3- https://anthrogenica.com/showthread....l=1#post336066
    nMonte sometimes has trouble spotting SSA in populations that have substantive Basal-Eurasian ancestry when you're modeling them with ancients like Natufians, Levant_Ns and so on. It can't even register the mild East-African in Samaritans and the notable amount in Yemenite Jews.

    4- http://eurogenes.blogspot.com/2016/0...an-puzzle.html
    TreeMix is conflicting with formal statistics in inferring SSA in Levant Neolithic.

    Gene flow from West Eurasia by a source high in Basal Eurasian would create these anomalies when modeling SSA levels in other populations, without taking into consideration that SSA itself is mixed.

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    So could we infer that a late out-of-Africa gene flow (maybe the one that brought E1b1b and some rare A, E1b1a and E1a Y-DNA lineages? E1b1b must've come from somewhere in the last 30,000 years) had a more important role in Paleolithic West Eurasia than previously thought, if the Eurasian-African genetic interaction contributed to most of the decrease in Neanderthal ancestry?

    By the way, is it possible that the 15000kya Moroccan Iberomaurusian-Natufian connection was out of Africa, and not from Southwest Asia into Africa, or can scientists really distinguish if the genetic movement was from the Levant to North Africa and not the other way around?

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