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Wednesday, February 17, 2016

Human pioneers interbred with Neanderthals ~100K years ago


Behind a paywall at Nature:

It has been shown that Neanderthals contributed genetically to modern humans outside Africa 47,000–65,000 years ago. Here we analyse the genomes of a Neanderthal and a Denisovan from the Altai Mountains in Siberia together with the sequences of chromosome 21 of two Neanderthals from Spain and Croatia. We find that a population that diverged early from other modern humans in Africa contributed genetically to the ancestors of Neanderthals from the Altai Mountains roughly 100,000 years ago. By contrast, we do not detect such a genetic contribution in the Denisovan or the two European Neanderthals. We conclude that in addition to later interbreeding events, the ancestors of Neanderthals from the Altai Mountains and early modern humans met and interbred, possibly in the Near East, many thousands of years earlier than previously thought.

Kuhlwilm et al., Ancient gene flow from early modern humans into Eastern Neanderthals, Nature (2016), published online 17 February 2016, doi:10.1038/nature16544

36 comments:

capra internetensis said...

So cool. Basically this is DNA from the >50 000 year old (Middle Paleolithic) anatomically-modern humans of Eurasia, via an ancient Neanderthal genome from Siberia.

And they aren't ancestral to modern Eurasians (or at least not the main line of ancestry). Which implies that there *was* a later Out-of-Africa.

Fingers crossed for an actual Middle Paleolithic AMH genome so we can check directly (it would take a lot of luck).

Rob said...

Ah yes excellent
So perhaps the earliest exodus of those early, pre-55 kya (?extinct)bAMHs found in Israeli sites did leave an imprint on Altaian Neandethals, but not European Neandethals or Denisovans.

Great finding

German Dziebel said...

Another completely artificial interpretation. A more simple interpretation is that Altai Neandertals carry a set of derived alleles shared with all of modern humans and a set of alleles shared only with non-Africans. Africans end up being just a subset of the EurasianHuman-Neandertal variation.

Rob said...

Oh, I see.
AMH came from North America ?

Davidski said...

Oh, I see.
AMH came from North America?


Yes, riding camels.

Rob said...

No I think it was moose.

Nirjhar007 said...

LOL

German Dziebel said...

@Rob

"AMH came from North America ?"

They had to speciate somewhere, right?

@Davidski

"Yes, riding camels."

Keep dreaming, amateur!

Davidski said...

@German

You're just kidding yourself if you don't think camels were involved in the Out-of-Americas push.

They had to be. I just know it.

Razib Khan said...

should get past paywall https://t.co/z4uoaN7ePP

Davidski said...

The read cube link did work for me earlier today, but it doesn't work now. It might just be me though, for whatever reason?

Rob said...

German
I agree that speciation had to occur somewhere, but America ? Acc. to archaeological evidence, humans have only been there for c. 15 k years.

Ype said...

This is a direct link to the complete article. http://www.nature.com/articles/nature16544.epdf?referrer_access_token=o5aDmvgYtIGYL2LdpEGlJtRgN0jAjWel9jnR3ZoTv0MInt_2jYvKBG--7sOqWdGTzUvToNHVvyhzE6mZLLgJJk-xwPlVu6cq_cgI4vcmhH2utoks_DbU5ieQAjiolCiOIQT10JeCT708MMEwLfMWg5GggbX6-6lZdnndQHTnvIcR5fAY4dyuZxaGTMgxuLcr&tracking_referrer=www.bbc.com

Matt said...

Thoughts on this paper:

- If these were AMH (Anatomically Modern Humans) and not a population who weren't phenotypically modern but related to AMH more closely than Neanderthal (which to me seems possible), then, if that's true, I guess that is another blow against the idea that there is a sparse base of a few particularly singular mutations within early AMH which set them apart from other hominins and were competitively superior. Because otherwise, you'd expect these would have introgressed into the Vindija population, and led to *them* colonising Eurasia, with no further takebacks from AMH.

- If you have AMH mixing with the Vindija ancestors and then not replacing them, it's harder to argue for AMH being competitively (behaviourally?) superior at that time. It's harder to argue that the whole AMH had a superiority over Neanderthals since earliest point of identification (or the admixture date, 100 KYBP), rather than specific groups of AMH with specific technology and culture later in history outcompeting / otherwise replacing Neanderthals.

Matt said...

Interesting PCA on variable sites from a sample of archaics and present day people (21, of which 10 are African) -

http://i.imgur.com/Ur9z3xU.png

PC1 - Neanderthal->Eurasian/American, PC2 - Neanderthal&Eurasian->African, PC3 - Neanderthal->Denisovan, PC4->Mbuti&San->other African

http://i.imgur.com/cRKIXn8.png - heatmap of correlations between their individual (10 Africans, 15 non-Africans); Neanderthals are pretty tight. Note the depths of the relative divergences?

Matt said...

introgressed into the Vindija population
Sorry, Altai Neanderthal, not Vindija.

Nirjhar007 said...

German,
I know you are very intelligent , I also like your approach. But, I am not getting what you are trying to say with AMH Coming from North America(?).
Can you give a short summary to me, showing what are the main points you observe, that make you suggest for such unique hypothesis?.

Davidski said...

And don't forget the camels.

FrankN said...

I am getting a bit lost with the chronology: They state that the AMH genetic introgression took place before or shortly after the first AMH genetic split, between San and all other AMH. That split is dated to around 200 ky. Similarly, their allele-based interference of the admixture period (Ext. Data Fig.5) has most positive counts in the 156-234 ka range.
The "100 ka ago"statement from the abstract appears to be a compromising with the archeological record/ theories, but in fact their analysis points at a much earlier timing that potentially questions everything we deem to know about early AMH prehistory. I actually wonder whether the admixture really took place in Eurasia, or there was a "back to Africa" move of some Neanderthals that later set off again in direction to the Altai.

Matt: "http://i.imgur.com/cRKIXn8.png - heatmap of correlations between their individual (10 Africans, 15 non-Africans); Neanderthals are pretty tight. Note the depths of the relative divergences?"

The heatmap holds a few surprises:

1. Satdinians are split into two populations. The first one branches off before other Europeans (represented by French), the second one from that European/French branch. Apparently, there's more to the Sardinian's genetic history than just Neolithic (EEF) continuity.

2.While branching off relatively early within Africans, Dinka stand out in their stronger relatedness to non-Africans, especially Europeans and Amerindians. The two Dinka individuals display a somehow differentiated pattern: The first one shows a stronger Oceanian-Amerindian, the second one a more European-Amerindian signal.

3. A recognisable European signal is also shown for one Mandinka and one Yoruba. That Yoruba furthermore shows a light Dai-Oceanian-Karitiana signal.

4. Even though San and Mbuti are fairly differentiated from the other AMH samples, their signals towards the whole AMH panel are still substantially stronger than those of Neanderthals and Denisovans. This probably implies an admixture rate in the range of 5% or more. Moreover, that admix doesn't seem to be equally distributed, which might be explainable as being basal, but fluctuates. Outside Africa, Oceanians appear to be least affected, Europeans plus one Han most.

5. All non-Africans show substantial heatmap signals with each other. One of the two Papuans appears to be the most neutral in this respect. Across continents, Asian-American signals are strongest, but the more basal (more ANE-like?) of the two French samples comes very close. Counter-intutitively, this French's signal is higher with Dai and Karitiana than with Han and Mixe.

@Dave: It's lamas, not camels!

Lank said...

@FrankN

They did find a good number of haplotypes lacking in the Denisovan that coalesce with modern Africans between <100 kya to 160 kya. Archaeologists have discovered migrations into Arabia since at least 125 kya. And despite modern Africans not being particularly related to the admixing population in the Altai Neanderthal, they do share some young haplotypes.

But yeah, no way to know if those early OOA migrants are the source, but we don't really have evidence of older populations.

FrankN said...

This seems an appropriate place to mention 2 AAPA 2016 abstracts I found noteworthy, also in relation to Matt's remark that "It's harder [now] to argue that the whole AMH had a superiority over Neanderthals":

Effects of adaptive Neandertal introgression at the OAS locus on the modern human innate immune response
AARON J. SAMS1, JOHANN NEDELEC2,3, ANNE DUMAIN2, VANIA YOTOVA2, PHILIPP W. MESSER1 and LUIS B. BARREIRO2,4.

It remains largely unclear to what extent this contribution from Neandertals (..) may have provided adaptive genetic variation to modern human populations. The immune system is one physiological system that harbors higher than typical amounts of genetic variation in order to provide a flexible set of responses to infection. Here we use coalescent simulation and population genetic approaches to demonstrate a signal of adaptive introgression in the 2'-5' oligoadenylate synthetase (OAS) gene cluster region of chromosome 12. The adaptive region encodes for three active OAS enzymes (OAS1-3) that are involved in the innate immune response to viral infection. In order to evaluate the functional consequences of the adaptive haplotype we infected primary macrophages and peripheral blood mononuclear cells from people with and without the Neandertal haplotype with a panel of viruses and viral-syntetic ligands. Our results show that people with the Neandertal-like haplotype show marked functional differences in the transcriptional regulation of OAS1 and OAS3 in response to virtually all viral agents tested, which illuminate the phenotypic effects of Neandertal haplotypes into the regulation of innate immune responses in modern human populations.

Ancient genetic diversity and an evolutionary medicine perspective on Neandertal extinction
ALEXIS P. SULLIVAN1 and GEORGE PERRY

The Eurasian sympatry of Neandertals and anatomically modern humans has long sparked anthropological interest in the factors that potentially contributed to Neandertal extinction. Among many different hypotheses, one extinction model is that modern humans and Neandertals were disproportionately affected by exposure to novel infectious diseases that were transmitted during the period of spatiotemporal sympatry. (..)
We compared levels of genetic diversity in genes for which genetic variation is hypothesized to benefit pathogen defense among Neandertals and African, European, and Asian modern humans, using available exome sequencing data (six chromosomes per population). Genetic diversity was estimated based on the number and allele frequencies of observed single nucleotide polymorphisms (SNPs) per population. We observed that Neandertal genetic diversity was relatively low in 73 innate immune system genes. In contrast, Neandertals and humans have similar levels and patterns of genetic diversity in nine major histocompatibility complex (MHC) genes. Thus, Neandertals may have been relatively more susceptible to some novel pathogens; differential pathogen-resistance should be considered as one potential contributing factor in their extinction, albeit cautiously.


If I understand that correctly: AMH have been able to successfully incorporate Neandertal genes for improved antiviral response, but that didn't work the other way round. So, possibly, when it got could during LGM and the Younger Dryas, both caught a flu. AMH survived, after some coughing and sneezing, the Neandertals didn't.

Matt said...

One of the interesting things about this paper is the mention that "The number of putatively introgressed segments in the Altai Neanderthal decreases in regions of the genome under strong purifying selection, and it is lower in the X chromosome compared to the autosomes. Because purifying selection purges deleterious alleles, and the efficacy of purifying selection is higher on the X chromosomes, this may indicate that modern human and Neanderthal alleles were often not tolerated in each other's genetic background".

This is interesting in the light of IIRC, papers suggesting that Neanderthals carried a higher genetic load than AMH (due to a smaller population size), and that purifying selection against Neanderthal variants was present in Eurasian AMH, based on this scenario.

For example - http://biorxiv.org/content/biorxiv/early/2015/11/21/030148.full.pdf - The Strength of Selection Against Neanderthal Introgression - "We find that the bulk of purifying selection against Neanderthal ancestry is best understood as acting on many weakly deleterious alleles. We propose that the majority of these alleles were effectively neutral—and segregating at high frequency—in Neanderthals, but became selected against after entering human populations of much larger effective size. While individually of small effect, these alleles potentially imposed a heavy genetic load on the early-generation human–Neanderthal hybrids. This work suggests that differences in effective population size may play a far more important role in shaping levels of introgression than previously thought.".

Yet if we find a similar scenario on introgression into Neanderthal, so does this affect our assumptions about how likely that is to be true? If Neanderthal variants are being purified out of AMH because, compared to AMH variants, they tend to be more deleterious on both AMH and Neanderthal background, then why are AMH variants being purified from a Neanderthal background (if in theory they are fitness improving)?

Grey said...

FrankN

"Apparently, there's more to the Sardinian's genetic history than just Neolithic (EEF) continuity."

The interior mountainous region is different from the surrounding coast.

http://www.nature.com/ejhg/journal/v11/n10/full/5201040a.html

Grey said...

(OoA) Out of Afr...Amer...Altai

Ryan said...

@FrankN - I think the general idea is that this new group split from other AMH around 200kya, but didn't mix with the Altai Neanderthals' ancestors until 100kya.

Ryan said...

@David - clearly we road lions out of Africa instead. :3

(They did actually spread at about the same time I believe.)

Fear me.

http://img.thesun.co.uk/aidemitlum/archive/00769/SNN3121A-682_769231a.jpg

German Dziebel said...

@Davidski

"You're just kidding yourself if you don't think camels were involved in the Out-of-Americas push. They had to be. I just know it."

I'm already used to amateurs "knowing" things. Keep trying. But an easier way would be to go to school. A high school, for starters. Don't follow Dienekes's sad example of advancing scientific hypotheses on the basis of a little sliver of reason and knowledge that he's developed by sitting in front of a computer.

@Rob

"I agree that speciation had to occur somewhere, but America ? Acc. to archaeological evidence, humans have only been there for c. 15 k years."

We can't base our understanding of human prehistory on archaeology. It's a moving target. How can we even talk about it after we'd discovered a whole new species, Denisovan, available to us only thanks to a pinkie an a tooth and a new DNA extraction technology. (I wonder how many pinkies are out there in America?) Or after we had witnessed human archaeological record in Asia get boosts of 60K years at a time. The rate of archaeological recovery is just slower in Asia and America compared to Europe and Africa, for demographic and other reasons. In America, sites such as Topper are promising in terms of a 50K horizon. What archaeology does show us is that no modern humans entered America from Asia 12,000 years ago. We know that much, the rest is still to be unearthed.

@Nirjhar

"Can you give a short summary to me, showing what are the main points you observe, that make you suggest for such unique hypothesis?"

I'll get back to you later. I just came back to this thread and need a bit more time to respond.

German Dziebel said...

@Nirjhar

OK. I'm back. We are a unique species, and this makes a unique place of origin quite befitting. Out-of-America is built on an alignment between interdisciplinary sets of evidence. Linguistically and culturally (and this is important because language and culture are the hallmark of behavioral modernity), the New World (and Papua New Guinea) are the most diverse in terms of the number of linguistic stocks and isolates, etc. Genetically, the New World (and Papua New Guinea) have the world largest between-group (intergroup) diversity which is consistent with both the linguistic picture above and the demographic expectation of the earliest modern humans to have lived in small, highly mobile demes. (Geneticists have wrongly assumed that intragroup diversity is indicative of a population's age and hence they looked at Africa where intragroup diversity tends to be the highest, while intergroup diversity is modest.) Neandertals and Denisovans have intergroup diversity even higher than Amerindians, which supports the antiquity of the New World (followed by Papua New Guinean) population structure. Predictably, we find Amerindians and Papua New Guineans, among all living, modern human populations, displaying the greatest allele sharing (with some of the longest chunks in common) with Neandertals and Denisovans. The archaeological record is also consistent with low population size and density in the Americas, which slows down the rate of archaeological recovery in the Western Hemisphere. On the basis of these considerations, I hypothesize that modern humans descended from an East Eurasian hominin and speciated in the New World before migrating back to the Old World. I exclude PNG from the short-list of modern human homelands because of their geographical location, but technically they exhibit the same critical factors as the New World, which suggests that the earliest modern humans in the Old World went down a Circumpacific route in Southeast Asia and Oceania.

Davidski said...

@German

If you can't fit camels into your Out-of-America hypothesis, then it's just a lost cause frankly.

German Dziebel said...

@Davidski

I don't need to convince you. With your impeccable credentials you are much more useful to science in the role of an out of America denier than an out of America supporter.

Nirjhar007 said...

German,

I think you have written an article? or you are still working?. I find your ideas new, bold but importantly practical.

Davidski said...

But importantly practical.

Holy shit.

Nirjhar007 said...

BTW German,
Do you know this guy?
https://plus.google.com/100700019181275995409

Karl_K said...

@Davidski

" 'But importantly practical. '

Holy shit."

I have to agree. That is some quality analysis. Some Holy Shit.

German Dziebel said...

@Nirjhar

"importantly practical."

Holy shit, that's the first time I hear this. I do know Gary Moore. His treatment of linguistic data is unsound, though. I wrote a book a while ago called The Genius of Kinship. It's on Amazon. It needs to be updated in the line of recent genetic, etc. evidence, and writing books these days makes you always behind on the new data.

@Karl

"I have to agree. That is some quality analysis. Some Holy Shit."

What Nirjhar is trying to say is that out-of-America, unlike out-of-Africa, is effective in linking together in an organic and logical fashion different kinds of evidence (cultural, genetic, archaeological). Out-of-Africa has to use cultural stereotypes of thinking about human origins and the peopling of the Americas to link everything into an awkward and constantly-falsified whole.

batman said...

If modern humans didn’t reach Europe until about 60,000 years ago, how has DNA from them turned up in a Neanderthal fossil in Germany from 124,000 years ago?