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Thread: Royal Society Paper Casts Doubt on Neanderthal/Denisovan Genes in Modern Humans

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    Royal Society Paper Casts Doubt on Neanderthal/Denisovan Genes in Modern Humans

    Cambridge Professor William Amos has had another paper published on human origins. Specifically his hypothesis is that living humans do NOT carry any appreciable genetic signal from introgression with Neanderthals and Denisovans. If it happened in the past it was a mistake nature quickly fixed. Rather, mutation rates differ in populations and Africans drifted further from archaic populations than did Eurasians due to a higher mutation rate.

    He has many convincing papers on this, and I find some they will not publish for vague reasons even more convincing that the ones they will deign to publish, but here is his second one. He uses several lines of evidence, some stronger than the others IMHO. One of them is that using the same methods they use to infer introgression from archaics can also be used to show introgression from each of the great apes!

    Did humanity began as a distinct population? For some reason, the scientific establishment seems to be against this idea very strongly. The introgression hypothesis has been, in my view, "pushed" out of proportion to the hard evidence for it. Yet we have seen recently how wrong they can be regarding the origins of the virus. We should keep an open mind and follow the evidence. Here is some from Dr. Amos. https://royalsocietypublishing.org/d...98/rsos.201229

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    Quote Originally Posted by Cosmo View Post
    Cambridge Professor William Amos has had another paper published on human origins. Specifically his hypothesis is that living humans do NOT carry any appreciable genetic signal from introgression with Neanderthals and Denisovans. If it happened in the past it was a mistake nature quickly fixed. Rather, mutation rates differ in populations and Africans drifted further from archaic populations than did Eurasians due to a higher mutation rate.
    1) How exactly is/was admixture with other Homo species a "mistake"?
    2) Genetic drift and mutation rates don't and can't explain why there are specific variants and genes shared by Eurasians and Neanderthals/Denisovans to the exclusion of SSAs.

    Did humanity began as a distinct population? For some reason, the scientific establishment seems to be against this idea very strongly. The introgression hypothesis has been, in my view, "pushed" out of proportion to the hard evidence for it. Yet we have seen recently how wrong they can be regarding the origins of the virus. We should keep an open mind and follow the evidence.
    What are you even talking about? The null hypothesis in the field for decades was the full replacement/no introgression model, until archaeogenomics proved that otherwise (after years of debate and denial of evidence!). The 98% replacement/2% introgression model for Eurasians is the compromise that came out of that.
    Last edited by leorcooper19; 06-17-2021 at 07:25 PM. Reason: fixed quote
     
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    It seems to me (and I am just a mug amateur on this topic), that there are two means of establishing Neanderthal or Denisovan introgression.
    One is to directly compare Neanderthal or Denisovan DNA with modern human DNA or historical AMH from human remains.
    The second is to infer it from statistical analysis.
    Professor Amos's two papers, as far as I can see, do not at all address the first method, although I would have expected him to say that.
    He questions the second method, because he can just as easily reach other conclusions from it.

    It's good that methodology is questioned, because in the past there have been many cases of us seeing what we would like to see.
    And I don't even know whether his statistics are correct or not, but I would hope that the referees have seen to that.
    What he should be stating is that his approach does not say that there is no Neanderthal / Denisovan in us, just that one method used to measure that may be flawed.

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    Quote Originally Posted by leorcooper19 View Post
    1) How exactly is/was admixture with other Homo species a "mistake"?
    2) Genetic drift and mutation rates don't and can't explain why there are specific variants and genes shared by Eurasians and Neanderthals/Denisovans to the exclusion of SSAs.
    1) I mean that there were barriers to successful hybridization and that if some crosses were fertile nature took them out of the gene pool so that all of the supposed "signal" of introgression in living humans today can be explained by varying mutation rates in populations. Much like there are no ligers in the wild and we don't find evidence of recent tiger introgression into lions or vice versa.

    2) They do though. Dr. Amos has a profound explanation for it and some of his unpublished work say it more clearly than this one. Back mutations happen. If the small homogenous group that left Africa (Dr. Amos says there may have been two) had very high homozygosity in their genes then they would have a much lower mutation rate than populations which were highly heterozygous. So over time the SSA population would evolve away faster from the condition. Including back-mutating in some places where the smaller, lower mutation-rate group did not. This produces a false signal of introgression. I would add that in terms of positive selection, Eurasians were exposed to the same environment as Neanderthals while SSA were pushed in a different direction against different pathogens.

    Imagine Africans had a large diverse populations with some genes more like Neanderthals in a minority of individuals. A subset of that population, especially if related, could have those genes which are a minority in the original group quickly move to fixation in the subgroup. Then the minority allele gets lost in the main group due to drift because it was always a small minority. In the subgroup, it is preserved because it happened to make up a larger share of that group.

    At any rate, you are quoting the party line when you say "they can't" explain the genetics. Perhaps it would be more helpful to share where you think Dr. Amos' reasons why they CAN explain it are off base?

    Quote Originally Posted by leorcooper19 View Post
    What are you even talking about? The null hypothesis in the field for decades was the full replacement/no introgression model, until archaeogenomics proved that otherwise (after years of debate and denial of evidence!). The 98% replacement/2% introgression model for Eurasians is the compromise that came out of that.
    I mean just what I say. I am talking about this decade, not decades past. I think the pendulum swings one way and then another on many questions. But lately on this question it may have become stuck. I think it needs to keep swinging and that this aids the search for truth. Maybe it is too early for theory to become dogma, if it ever should.

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    Quote Originally Posted by Saetro View Post
    It seems to me (and I am just a mug amateur on this topic), that there are two means of establishing Neanderthal or Denisovan introgression.
    One is to directly compare Neanderthal or Denisovan DNA with modern human DNA or historical AMH from human remains.
    The second is to infer it from statistical analysis.
    Professor Amos's two papers, as far as I can see, do not at all address the first method, .......
    I've had him say to me privately when I've asked him about this that studies show that mutations cluster. And if you look at the latest on his page of papers that have not been published to you will see he goes beyond D stat analysis. I assume by "direct comparison" you mean clusters that are the same and not just individual alleles? I think some of his work is now looking at that, and confirms his conclusions drawn from stats.... https://www.researchgate.net/project...ke-and-mirrors

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    Quote Originally Posted by Cosmo View Post
    1) I mean that there were barriers to successful hybridization and that if some crosses were fertile nature took them out of the gene pool so that all of the supposed "signal" of introgression in living humans today can be explained by varying mutation rates in populations. Much like there are no ligers in the wild and we don't find evidence of recent tiger introgression into lions or vice versa.
    The fact that we have ancients like the individual from Oase with recent Neanderthal (but not gen1) ancestry shows how wrong this is.

    2) They do though. Dr. Amos has a profound explanation for it and some of his unpublished work say it more clearly than this one. Back mutations happen. If the small homogenous group that left Africa (Dr. Amos says there may have been two) had very high homozygosity in their genes then they would have a much lower mutation rate than populations which were highly heterozygous. So over time the SSA population would evolve away faster from the condition. Including back-mutating in some places where the smaller, lower mutation-rate group did not. This produces a false signal of introgression. I would add that in terms of positive selection, Eurasians were exposed to the same environment as Neanderthals while SSA were pushed in a different direction against different pathogens.
    Don't be offended that I can't help but find this explanation less than "profound." One, how exactly does homogeneity lower the rate of random mutation? Could you cite some scholarship (preferably not from Dr. Amos) that goes into this? Two, back mutation/convergence can explain some things, but cannot explain rates like 1-2% of the whole genome shared across thousands of variants. That's way past the realm of reasonable convergence.

    Imagine Africans had a large diverse populations with some genes more like Neanderthals in a minority of individuals. A subset of that population, especially if related, could have those genes which are a minority in the original group quickly move to fixation in the subgroup. Then the minority allele gets lost in the main group due to drift because it was always a small minority. In the subgroup, it is preserved because it happened to make up a larger share of that group.
    Yes, genetic drift is extremely powerful. But wouldn't you say it'd be a huge coincidence that Eurasians preserved thousands of ancestral variants that all became derived in all SSAs (who, I don't need to explain, should not be thought of as a monolith, especially in this context) that Neanderthals/Denisovans happened to also share, despite them also being divergent populations with their own genetic drift? Why should we need to bend over backwards to explain this?

    At any rate, you are quoting the party line when you say "they can't" explain the genetics. Perhaps it would be more helpful to share where you think Dr. Amos' reasons why they CAN explain it are off base?

    I mean just what I say. I am talking about this decade, not decades past. I think the pendulum swings one way and then another on many questions. But lately on this question it may have become stuck. I think it needs to keep swinging and that this aids the search for truth. Maybe it is too early for theory to become dogma, if it ever should.
    This is 2021. We now have studies like Gopolan et al. that continue to show just how airtight this (tiny!) contribution was. Yes, science is always changing/evolving/improving, but at some point the use of that argument goes from productive to counterproductive.
     
    My avatar is paleoart of a Neanderthal child by Tom Björklund, check him out: Hidden Content

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    Quote Originally Posted by leorcooper19 View Post
    The fact that we have ancients like the individual from Oase with recent Neanderthal (but not gen1) ancestry shows how wrong this is.
    Then how wrong is it really? Doesn't Robert Reich say that this population left no impact on modern human populations? A dead end IOW. That is not really in conflict with what I said but rather a data point suggesting reduced fitness in such hybrids.



    Quote Originally Posted by leorcooper19 View Post
    Don't be offended that I can't help but find this explanation less than "profound." One, how exactly does homogeneity lower the rate of random mutation? Could you cite some scholarship (preferably not from Dr. Amos) that goes into this? Two, back mutation/convergence can explain some things, but cannot explain rates like 1-2% of the whole genome shared across thousands of variants. That's way past the realm of reasonable convergence.
    No offense on my part. Different alleles recombine with a higher error rate because they don't match up as well as when alleles are identical. Yes I can show you other research which indicates homogeneity affects mutation rate and I've not got to go far to do so. Dr. Amos gives four cites in his paper, two from him and two from others. The others are Harris K. 2015Evidence for recent, population-specific evolution of the human mutation rate. Proc. Natl Acad. Sci. USA 112, 3439-3444. (doi:10.1073/pnas.1418652112) Crossref, PubMed, ISI, Google Scholar
    35.
    Harris K, Pritchard JK. 2017Rapid evolution of the human mutation spectrum. eLife 6, e24284. (doi:10.7554/eLife.24284) Crossref, PubMed, ISI, Google Scholar



    Quote Originally Posted by leorcooper19 View Post
    Yes, genetic drift is extremely powerful. But wouldn't you say it'd be a huge coincidence that Eurasians preserved thousands of ancestral variants that all became derived in all SSAs (who, I don't need to explain, should not be thought of as a monolith, especially in this context) that Neanderthals/Denisovans happened to also share, despite them also being divergent populations with their own genetic drift? Why should we need to bend over backwards to explain this?
    How is this different from argument from incredulity? Once a small sub population separates from large one to another environment, every gene is subject to drift at the same time. It is not extraordinary that the two populations would go in different directions once separated. The new X factor is whether drift is SLOWER in small homogenous populations. If this is the case, then drift is slower. It is therefore not unreasonable to expect that the population which drifted less looks more like an ancestral population than one which drifted more.

    And that's just drift. Positive selection should also drive Eurasian genes in the same direction as Neanderthal genes since they lived in a similar environment which was different from SSA. You want papers not from W Amos, try this one- Woolley Mammoths and Neanderthals had some of the same genetic changes as both species adapted to a cold environment. Clearly this alignment was NOT due to introgression but would be counted as such if applied to modern Europeans and Neanderthals. Gopolan et al. that continue to show just how airtight this (tiny!) contribution was. Yes, science is always changing/evolving/improving, but at some point the use of that argument goes from productive to counterproductive.[/QUOTE]"]https://www.jstor.org/stable/10.13110/humanbiology.90.2.03?seq=1#page_scan_tab_contents




    Quote Originally Posted by leorcooper19 View Post
    This is 2021. We now have studies like Gopolan et al. that continue to show just how airtight this (tiny!) contribution was. Yes, science is always changing/evolving/improving, but at some point the use of that argument goes from productive to counterproductive.
    I hope to look over your link in more detail when I can, but it starts off with MTDA arguments which would be helped immensely if we found some ancient human remains with Neanderthal MTDNA. It is basically arguing we can't find it today maybe because it drifted out of the population. But we have no data points which show it IN the population of HS to start with.

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    As stated by leorcooper... Africans are not a monolith. If Neanderthal introgression is alleged as an artifact of high homozygosity in Eurasians, why wouldn't different African populations each drifting their merry ways not 'preserve' a unique subset of 'Neanderthal variation' in the areas they hadn't mutated yet? Surely Eurasians after 50,000+ years have not undergone 0 mutation, so Africans should share some 'Neanderthal introgression' that Eurasians don't, just less.

    Not to mention the problem Denisovans and their differential relatedness to Eurasians brings into this.
    Last edited by Kale; 06-18-2021 at 04:51 AM.
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    Quote Originally Posted by Cosmo View Post
    I've had him say to me privately when I've asked him about this that studies show that mutations cluster. And if you look at the latest on his page of papers that have not been published to you will see he goes beyond D stat analysis. I assume by "direct comparison" you mean clusters that are the same and not just individual alleles? I think some of his work is now looking at that, and confirms his conclusions drawn from stats.... https://www.researchgate.net/project...ke-and-mirrors
    Sorry, not seeing it among the matters at the link you posted.
    Any reference to mutation seems to be about how that might influence the D stat analysis, so we are still back at the statistical method approach, with maybe a slight costume change.
    I'm still not saying he's wrong. Just that there is still basically just one approach in anything I have seen from him.
    If there is more unpublished stuff then I await the revelations with great anticipation.

    And I think the lack of response from academia may well be driven by there being no reward in it.
    Getting a new paper out about yet another connection with Denisovans is a positive career move.
    Getting bogged down in a dispute over methodology is a time eater that will chew up opportunities for that and other work as well.
    It won't get you on the evening news, or the online equivalent.

    My point is that 1) if Amos is right, academics will probably not engage.
    2) if Amos is wrong, academics will tend not to engage anyway, because there is nothing in it for them.
    So the absence of a counter does not necessarily support Amos.

    Or maybe they are taking their time to respond.
    Maybe we just need to wait and see if there is an academic counter, and see what it says.
    Last edited by Saetro; 06-18-2021 at 07:39 PM.

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    2) Idk overturning years of orthodoxy seems to be pretty newsworthy.
    Collection of 14,000 d-stats: Hidden Content Part 2: Hidden Content Part 3: Hidden Content PM me for d-stats, qpadm, qpgraph, or f3-outgroup nmonte models.

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