January 29, 2014

Neandertal admixture in modern humans: some of it adaptive, some selected-against (Sankararaman et al. 2014)

From this paper, this should be of interest for those who argue if they are .1 or .2% more/less Neandertal than others based on commercial testing results:
Fourth, the standard deviation in Neanderthal ancestry among individuals from within the same population is 0.06–0.10%, in line with theoretical expectation (Supplementary Information section 3), showing that Neanderthal ancestry calculators that estimate differences on the order of a per cent18 are largely inferring statistical noise.
Also of interest, showing that while overall Neandertal ancestry in Eurasians is low (1+%), this average includes region where it is much higher, and indeed the majority:
The Neanderthal introgression map reveals locations where Neanderthal ancestry is inferred to be as high as 62% in east-Asian and 64% in European populations (Fig. 1b and Extended Data Fig. 2).
Finally:
We have shown that interbreeding of Neanderthals and modern humans introduced alleles onto the modern human genetic background that were not tolerated, which probably resulted in part from their contributing to male hybrid sterility. The resulting reduction in Neanderthal ancestry was quantitatively large: in the fifth of the genome with highest B, Neanderthal ancestry is 1.5460.15 times the genomewide average (Extended Data Table 4 and Supplementary Information section 9)22. If we assume that this subset of the genome was unaffected by selection, this implies that the proportion of Neanderthal ancestry shortly after introgression must have been >3%rather than the approximately 2% seen today. 
One of the lingering questions about Neandertal admixture is why there are no Neandertal Y-chromosomes or mtDNA in modern Eurasians. The disappearance of Neandertal mtDNA seems unlikely according to one study, but might be explained if negative selection was at play.

A different question is whether hybrid sterility was actually noticed by modern humans/Neandertals during the period of admixture. Modern societies have historically frowned upon mixture between diverged sapiens populations, even though there is no evidence that the offspring of, say, an African and a European are biologically disadvantaged. But, in the case of sapiens-Neandertal crossings, the offspring would have been biologically disadvantaged, a fact that may have been noticed over the span of a few generations.

Regardless of the historical dynamics of the admixture process, some of the Neandertal genome proved itself useful in its new sapiens hosts, and while the process may have been painful for the people involved, evolution found a way to use at least some of the material introduced to our species by our Neandertal cousins.

Nature (2014) doi:10.1038/nature12961

The genomic landscape of Neanderthal ancestry in present-day humans

Sriram Sankararaman

Genomic studies have shown that Neanderthals interbred with modern humans, and that non-Africans today are the products of this mixture1, 2. The antiquity of Neanderthal gene flow into modern humans means that genomic regions that derive from Neanderthals in any one human today are usually less than a hundred kilobases in size. However, Neanderthal haplotypes are also distinctive enough that several studies have been able to detect Neanderthal ancestry at specific loci1, 3, 4, 5, 6, 7, 8. We systematically infer Neanderthal haplotypes in the genomes of 1,004 present-day humans9. Regions that harbour a high frequency of Neanderthal alleles are enriched for genes affecting keratin filaments, suggesting that Neanderthal alleles may have helped modern humans to adapt to non-African environments. We identify multiple Neanderthal-derived alleles that confer risk for disease, suggesting that Neanderthal alleles continue to shape human biology. An unexpected finding is that regions with reduced Neanderthal ancestry are enriched in genes, implying selection to remove genetic material derived from Neanderthals. Genes that are more highly expressed in testes than in any other tissue are especially reduced in Neanderthal ancestry, and there is an approximately fivefold reduction of Neanderthal ancestry on the X chromosome, which is known from studies of diverse species to be especially dense in male hybrid sterility genes10, 11, 12. These results suggest that part of the explanation for genomic regions of reduced Neanderthal ancestry is Neanderthal alleles that caused decreased fertility in males when moved to a modern human genetic background.

Link

26 comments:

Keith Minto said...

"Regions that harbour a high frequency of Neanderthal alleles are enriched for genes affecting keratin filaments, suggesting that Neanderthal alleles may have helped modern humans to adapt to non-African environments."

Intriguing ! If anyone can elaborate on this it would be very welcome.

laptopgenomics said...

Can't the lack of Neanderthal mtDNA and very low frequency of Neanderthal DNA in X chromosome in modern humans simply mean that the interbreeding was mostly of Neanderthal men and H. sapien women type?

andrew said...

Re Y-DNA and mtDNA

Male hybrid sterility removes Neanderthal Y-DNA from the modern human populations.

Mothers of hybrids do not have long term relationships with the fathers and are therefore matrilocal. Human mothers give birth to their hybrid children with modern human mtDNA in human tribes. Neanderthal mothers give birth to their hybrid children with Neanderthal mtDNA in Neanderthal tribes that subsequently go extinct. (Male hybrid sterility probably keeps modern human Y-DNA out of these Neanderthal tribes as well).

Ergo, no Neanderthal Y-DNA or mtDNA survives in modern humans.

Why don't Neanderthals and modern humans form long term relationships? Different cultures, different languages, etc. Strong endogamy preferences are already common when very different modern human groups co-exist and would e stronger between groups as different as Cro-Magnons and Neanderthals.

Some pregnancies may be products of rape, others of brief affairs when modern human and Neanderthal tribes are temporarily nearby each other.

Grey said...

"an approximately fivefold reduction of Neanderthal ancestry on the X chromosome"

Miscarriage?

terryt said...

"Neanderthal alleles may have helped modern humans to adapt to non-African environments".

I would have though that was extremely likely to be so.

"An unexpected finding is that regions with reduced Neanderthal ancestry are enriched in genes, implying selection to remove genetic material derived from Neanderthals".

Possibly getting rid of the 'ugly' genes.

"there is an approximately fivefold reduction of Neanderthal ancestry on the X chromosome, which is known from studies of diverse species to be especially dense in male hybrid sterility genes"

Andrew has always thought that to be very likely. He'll be pleased to have his idea shown to be likely. In hybids between most progressively different species male fertility is the first thing that gives out. I actually though Neanderthals and modern humans were genetically closer than this study suggests.

zardos said...

What about hair shape? That's the first thing which came to my mind, considering the obvious differences between Eurasians and Subsaharan Africans.

Hamar Fox said...

Intra-regional variation seems slight where admixture with higher or lower-scoring populations is absent. Finns as the highest and Spaniards as the lowest scoring Europeans included may reflect moderate East Asian and minor SSA ancestry in those populations respectively relative to the other European populations. Or it may reflect an original North/South cline of Neanderthal admixture in Europe, possibly related to higher Neanderthal admixture in hunter gatherer populations, as suggested by Dienekes' analysis of Otzi.

Hamar Fox said...

Oops, I meant Iberians, not Spanish in particular. Also, when I said they had 'low SSA relative to the Europeans', the phrasing was confusing. I meant higher than the other groups, but still low.

Matt said...

What's not clear from the abstracts and coverage and which I'd find interesting is

- how many of the Neanderthal negative selected alleles are variants they shared with Denisovans, but not modern humans?

- how many of the Neanderthal positive selected alleles are unique to them and not shared with Denisovans or modern humans?

That is, whether the Neanderthal negative selected alleles tend more to be uniquely Neanderthal variants, or the generally "archaic" variants.

I'd expect the Neanderthal variants that are positively selected in Eurasians (at least those Eurasians with fairly similar cool habitats) to be the "uniquely Neanderthal" stuff, while the negative selective variants are the "generically archaic" stuff.

Monamann11 said...

Biologically speaking, how likely or unlikely is it that YAP+ is a signal/marker of Neanderthal => AMH introgression?

Is there info on the amount of Neanerthal DNA carried by Amerindians?

Mark Moore (Moderator) said...

Too bad we haven't got mtDNA sequencing for Neandertals, because that would test which explanation is correct between Andrew and laptop. If we found human mtDNA in a Neandertal then Andrew's idea is correct, if not, laptops.

For my own reasons, I am thinking laptop is on the right track. Neandertal women would not meet a human male's idea of beauty at all, while the human female may not have had much choice in the matter.

andrew said...

"Andrew has always thought that to be very likely. He'll be pleased to have his idea shown to be likely."

I am.

"how likely or unlikely is it that YAP+ is a signal/marker of Neanderthal => AMH introgression?"

Not likely. YAP+ is present in Africans with Y-DNA hg E. For the most part, these Africans have little or no Neanderthal DNA. YAP+ is also present in Asians with Y-DNA hg D, the most numerous of which in modern populations are the Japanese. They have typical East Asian levels of Neanderthal DNA.

"Is there info on the amount of Neanerthal DNA carried by Amerindians?""

IIRC, this is more or less identical to that of East Asians.

"Too bad we haven't got mtDNA sequencing for Neandertals"

IRRC, we have quite a few ancient DNA samples of Neanderthal mtDNA. None of that Neanderthal mtDNA involved AMH lineages, and no modern human DNA modern or ancient is from a Neanderthal sequence.

The best evidence for the existing of AMH admixture in Neanderthals involves some of the late transitional tool cultures that are intermediate between Neanderthal Mousterian and post-Neanderthal extinction modern human tool cultures that appear at almost the same historical moment as Neanderthal-modern human first contact and have subsequently confirmed to be found only in Neanderthal sites. The imperfect behavioral shift towards AMH patterns for the brief period from first contact between AMH and Neanderthals in Europe, and their extinction, could be easily be explained through the influence of hybrid individuals in Neanderthal communities (who would lack AMH mtDNA for the same reason that I propose that no Neanderthal mtDNA survives in human populations - matrilocality of hybrid mothers).


Annie Mouse said...

"For my own reasons, I am thinking laptop is on the right track. Neandertal women would not meet a human male's idea of beauty at all, while the human female may not have had much choice in the matter."

The physical appearance argument does not cut it. Firstly taste in women varies, even now. A much fuller-figured woman used to be the ideal in the recent past for example, and still is for some. I once met a man who told me the fist thing he looked for in his ideal woman was large teeth! Not all men like women who look like anorexic boys in drag.

Secondly I don't think neanderthal women would have looked all that different. And I can't imagine many men would throw the neanderthal lady in the image below out of bed.

http://www.oglekin.org/Paleontology/Neanderthal/Images/Neandertahal-03.jpg

Thirdly have you seen what some men will sleep with? There are several STDs that will say that there are very few limits.

Finally I doubt neanderthal man was any more likely to be a rapist than Homo sapiens, despite the Jean Auel books. Children of rape don't tend to survive well. It is not a good propagation strategy.

Plenty of big-boned, coarsely masculine men do just fine with women. And have you seen Donald Trump's wife? Or any number of elderly billionaires spouses. Women are not much into classically handsome looks, they make choices for other reasons.

eurologist said...

Biologically speaking, how likely or unlikely is it that YAP+ is a signal/marker of Neanderthal => AMH introgression?

Monamann11,

Impossible, because Neanderthals don't share the modern human y-tree, and we are talking about the non-recombining portion.

Too bad we haven't got mtDNA sequencing for Neandertals

Mark Moore,

But we do. They are more closely related to modern humans than to heidelbergensis (Atapuerca or Denisova), but still rather removed from the known extant human mtDNA tree.

Grey said...

"Neandertal women would not meet a human male's idea of beauty at all"

We're not talking modern looking humans here. The reconstructions of early modern humans are no closer to my idea of a good time than Neanderthals are.

.

"Finally I doubt neanderthal man was any more likely to be a rapist than Homo sapiens, despite the Jean Auel books. Children of rape don't tend to survive well. It is not a good propagation strategy."

I think more violent times would have led to a higher frequency of violent traits but either way rape as a reproductive strategy can only work well in environments where women can feed their kids themselves.

If anything, more extreme environments ought to select against sexual violence for that reason.

.

I think a simpler explanation is there was mixing on both sides - often the result of raiding and kidnap similar to say the American frontier - but the pregnancies and offspring had a lot of problems because they were genetically too diverged only surviving when they had a distinct advantage of some kind.

terryt said...

"Not all men like women who look like anorexic boys in drag".

My own theory as to why most fashion models 'look like anorexic boys in drag' is that the industry is dominated to a large extent by homosexual males. 'Skinny' women are not most men's prefered look.

"Thirdly have you seen what some men will sleep with? There are several STDs that will say that there are very few limits".

To me that has always been the clinching argument against the idea modern human men would not have mated with Neanderthal women.

1Marcelo said...

And there goes Mark Moore again injecting his personal bias in an ignorant comment. Annie Mouse, in contrast, nails it with a fact-based explanation.

Monamann11 said...

Andrew and Eurologist, “yes” and “yes,” but my question concerns reproductive biology: Is there any evidence that some kind of stress associated with hybridization in other species results in mutations like the YAP UEP? Since a) this TYPE of mutation, unlike SNP’s, has occurred only once among billions of human males whose Y chromosomes were passed along via reproduction; b) The mutation occurred at roughly the same time depth as AMH-Archaic meetups; and c) YAP+ has left a legacy in extant humans at ballpark-similar rates as archaic DNA. So…. Just wondering, is that all simply coincidental? (I do realize that certainly might be the case!) (Andrew, I’m aware of the demographics and geographics of Hg E, but that pesky wildcard Hg D and its prominence on the Tibetan plateau might still be problematic.) (Eurologist, didn’t mean to imply I thought archaic DNA was somehow making a reappearance. Rather, what caused YAP? Was it a purely random, chance event, or can hybridization mutations occur that look like YAP+, caused by, for instance, some string of epigenetic conditions? I’m no biologist, & haven’t found info online.)

Russell said...

While I think it's reasonable to conclude that sapiens sapiens will mate anything they can, that presupposes two things.
Firstly that neanderthal women would find sapiens sapiens males attractive, a requirement if the neanderthal females were robust enough to resist rape.
Secondly while the male will mate with anything, there is no doubt that he will expend much more energy attempting to mate with a desirable woman. Independent of body shape, too much difference is usually thought to be unattractive.

Mark for Summit/Sunnoco said...

To several: Thank you for correcting me, we do have Neandertal mtDNA.

That is contains no admixture from humans (homos sapiens sapiens0 to me is clear evidence for laptop's idea is correct. That is, Neandertal males may have mated with human females, but the reverse was very rare or did not happen (or did not produce a viable fetus.)

I can tell Andrew really knows his stuff, but I don't see the matri-local idea as being as good an explanation as laptop's. If it was only that there was no Neandertal mtDNA in modern humans it might be reasonable, but there also appears to be no human mtDNA in the Neandertal specimens we have.

Further, even if most small groups were matri-local, unless they ALL were, with no taking captives or changing sides as one clan or the other died off, there would be some mtDNA in modern humans.

Annie if the Neandertal women looked like that, ok, human males would have hit them if they had the chance- but how can we be sure? How do we know they were not covered in body hair?

Also, I don't think human males would hit on Neandertal women prior to the invention of beer, which is an important aid to poor-decision making in modern humans - that one was for you Marcelo!

terryt said...

"Since a) this TYPE of mutation, unlike SNP’s, has occurred only once among billions of human males whose Y chromosomes were passed along via reproduction"

I doubt it is by any means the 'only' mutation on the NRY that has occurred only once.

"Andrew, I’m aware of the demographics and geographics of Hg E, but that pesky wildcard Hg D and its prominence on the Tibetan plateau might still be problematic".

Yes, that discontinuity is extremely interesting. And from the latest Y-DNA C phylogeny we see C apparently having originated in the Far East as well, disconnected to anything in Africa. To me the most obvious explanation is that both DE and CF were members of a widely spread population until 'something' split the African population from the Far eastern one. That 'something' is unlikely to be anything that happened in South Asia (unless you're going to claim Toba). We are actually very well-aware of something that would have split a population spread through Central Asia however. A series of Ice Ages.

"what caused YAP? Was it a purely random, chance event"

I think that is extremely likely to be the explanation.

eurologist said...

Eurologist, didn’t mean to imply I thought archaic DNA was somehow making a reappearance. Rather, what caused YAP? Was it a purely random, chance event, or can hybridization mutations occur that look like YAP+, caused by, for instance, some string of epigenetic conditions? I’m no biologist, & haven’t found info online.

Monamann11,

The only mechanism I can think of is related to the fact that the non-recombining portion of the y-chromosome is actually non-contiguous; there are ~4-5 known (and perhaps additional unknown) regions interdispersed that do recombine with the x-chromosome. Combine that with a putative significantly different Neanderthal x-DNA, some perturbation in the replication process might occur in the vicinity of these recombining stretches.

You can google for papers on that topic and at least find out how close YAP+ is to any of the known regions. And please report back! ;)

If it was only that there was no Neandertal mtDNA in modern humans it might be reasonable, but there also appears to be no human mtDNA in the Neandertal specimens we have.

Mark,

That's not a strong argument, since we have so very few samples, and none from the time and region where the first contact most likely occurred (West Asia).

Annie if the Neandertal women looked like that, ok, human males would have hit them if they had the chance- but how can we be sure? How do we know they were not covered in body hair?

Those two pictures are from a contest, morphing famous people (guess who! ;)) into Neanderthals. The first one is rather realistic, IMO; the second one a bit less so, because she still has a chin.

Body hair is extremely unlikely, since model calculations have demonstrated that even stocky Neanderthals, even if we suppose Inuit-like subcutaneous fat, needed to be dressed even in the summer, and needed extreme measures to survive winter nights. Body hair would have been a detriment because of parasites and too much insulation (overheating) during strenuous activity in the sun in the summer. Many domesticated animals have lost the ability to produce winter coats or lost much or almost all of their fur in just a few thousand years, for similar reasons.

Curtis Christy said...

To Andrew on Jan 30 -- While rape must have occurred, the survivors of rape alone, would have been few, given that the act, itself, would imply enmity between the groups so that the victim would very likely also be killed, or would have been shunned by her own people--given the easy determination of fatherhood at birth. Shunned women in a hostile environment would either die or be taken into the tribe of those similar to the father of the child. Or, the child would probably have been killed so that the woman could remain with her own kind. The concept of "an affair" seems to bizarre to contemplate. A more likely scenario would have been one similar to that which caused so many African Americans to have Native American blood. That is that human women were most likely becoming pregnant by Neanderthal men because they were treated as commodities -- meaning that they were traded to Neanderthals, or that they were captured by Neanderthals, were "enslaved" by Neanderthals [on a system similar to that of the Cherokee, in which after a while ... once the urge to escape died down ... the captured or bartered woman would simply become one of the tribe--albeit a "second class citizen." But the child of the tribe--especially is some of the physical or mental featured brought by the human DNA was viewed as conferring a relatively higher status, then the hybrid
child might help to elevate the status of the human woman in the Neanderthal camp. Consider what happened to the Indians in the 16th Century [thanks to the Spanish] and during the 17th Century (thanks to everyone else) ... they started dying off from diseases. While some tribes virtually disappeared, other tribes survived but "morphed" into looking a great deal like their Euro-based neighbors. Why? Because while the European and African illnesses brought by the people and by their pigs, were killing off a huge proportion of the Native population, the surviving Indians were, nevertheless, ALSO continuing to live ... and took white and black women where they could, and also too African men and women--including runaways, captures, a barters, and purchases ... meaning slaves [and, yes, the Cherokee and other tribes of the Southwest had slaves]. But as many Indians died of disease and--let's face it--genocide, WHO in their tribes were most likely to live on? The "imports" and the hybrid children. Why? Immunity to the diseases that that were killing off the full-bloods. Many Native Americans are uncomfortable with this next bit, but it is obvious from the evidence in photographs. Look at the earliest group photographs of Indians of the Southeast. Many look white, and many look black. Read Forbes about "Black Indians." It's no myth, and no attempt to defame. It's just the effect of the social system--that included enslavement and adoption, as well as a general lack of racism [of the complexion-based kind], that allowed Indians to take in new members, and for the descendants of those new members to survive and--in effect--to "take over" by default as the full bloods died off. Not politically correct dinner conversation, but a scenario that may well have happened to the Neanderthal, as well. So that the diseases that we inherit from the Neanderthal might be viewed as their posthumous revenge for what contact with our human ancestors ultimately did to them.

Curtis Christy said...

Oh, and one more thing ... it would probably not have worked the same way in the other directions ... not because the Neanderthals didn't have diseases that the humans could catch ... we know that they did. but for two other reasons: (1) because the humans probably were not culturally in the habit of taking captives ... because they had "recently: immigrated, and would have been traveling and nomadic in a different way than the mammoth-following Neanderthals were. and (2) because the Neanderthals would have looked scary, strong, and threatening--even the women. The say that a chimp is much stronger than a man. How much stronger would Neanderthal have been compared to the relatively scrawny and lithe humans? And how many encounters between them would it have taken before the humans figured that out? One, maybe. If the Neanderthals' eyes were blue and green (as some have speculated), and if their complexion was light and their hair was light and long, maybe that would have reduced the fear factor a little bit--if only because it would have been intriguing for the new comer humans. But by and large, they were bigger, broader, with large teeth, big hands and feet, and would have scared the crap out of the average human. Would the humans have raped Neanderthal women? Well, they say that rape is an act of power, not sex. Maybe some of that kind of show of dominance could have happened, but doesn't that require us to see ancient humans as having been a bit more sophisticated--and psychologically cunning--than they probably were? No, if there were many unions between Neanderthal women and human men, it would probably have been due to the human having been captured (or bartered in) to the Neanderthal band, and given to a woman as a helper (read "slave" and all that might possibly imply. It is rare that women "rape" men--not to mention difficult to consummate. But it would not be difficult to imagine a human male being caught--perhaps as a boy, and raised among the Neanderthals, and having his taste altered by life experience. But a chance encounters with Geisela the 190 pound Neanderthal ... alone in the woods (!?) while the visually and alfactorally challenged human guy also just happened to be out there alone ... seems unlikely, to start with. And that he would survive the encounter AT ALL seems unlikely too. But if he tried to rape her?? Or even if he gave her flowers, how likely would he be to try to take her home to meet his mother? And how likely would the human family be to accept her at the hearth? Maybe that scenario can help to account why there have been gnawing teeth marks on some of the Neanderthal bones that have turned up over the years ... Geisela ended up staying for dinner. I mean, it just doesn't sound like there would have been as many Human Male - Neanderthal Female unions (with offspring) and Neanderthal Male - Human Female unions (with offspring) ... EVEN IF THE HYBRID STERILITY PROBLEM wasn't a factor. For what it's worth.

Curtis Christy said...

Sorry, one more point ... Jean Auel was right in the "Clan of the Cave Bear" theory. Those books should be dusted off and she should be elevated to the status of retro-prophet. Given how correct she was about the possibility for mixing of Neanderthals and Humans genes, I am willing to trust her thinking on other aspects of that relationship ... like the mutual distrust, the fear, etc. And yet, sometimes things happen. Remember not so long ago we were told that Neanderthal didn't have the facility of speech? Looks like that was wrong, too. Well, consider what Jean Auel says about how the Neanderthal augmented their communication (with each other): In her books, they had some kind of telepathic ability. I'm not saying that is true, but IF the gene flow went both ways in relatively equal proportions ... so that as many Human men made it with Neanderthal woman, as Neanderthal men made it with human women [which very likely would have been by some kind of force much of the time], the what BESIDES MUSCLE AND SCARINESS would have sealed the deal for a Human male with a Neanderthal female? Prestige? Trophy bride? Bragging rights? Curiosity? Neander-fever? Fetish compulsion? I doubt it was any of those. But it MIGHT have been personality, or something about the way she smiled. Or her come-hither look ... along with a post-hypnotic suggestion or something below the conscious level of understanding that our Neanderthal ancestors knew how to use, but which was not passed on to us ... except as that huge proportion of our brains that has no know use ... any more. Just thinking out loud. Sorry if I have inadvertently offended anyone. Signed, Curtis ... a Melungeon descendant.

Daria Khaltourina said...

"The Neanderthal introgression map reveals locations where Neanderthal ancestry is inferred to be as high as 62% in east-Asian and 64% in European populations (Fig. 1b and Extended Data Fig. 2)."
This does not look plausible. There were so many millenia to mix.
BTW, who they are?