February 19, 2016

Archaic introgression in Pygmies

We must remember that detecting archaic admixture in Africa is a statistical power game where only a particular type of such introgression can be detected:

First, it needs to be from highly diverged Palaeoafrican sources so that it will look very different from plain H. sapiens DNA. Unlike Eurasia, there's no genome of an ancient Palaeoafrican one can compare against. All inference is based on African genomes having an improbable amount of heterozygosity in parts of their genome.

Second, it needs to have happened recently enough so that it will come in big chunks that can be distinguished from the plain H. sapiens background. Given enough time, recombination breaks down archaic segments into ever tinier bits. You can argue that an unusually long divergent haplotype with a deep TMRCA is archaic, but you can't argue that a single SNP is.

I have little doubt that most if not all of the supposedly "old divergences" between African populations are a mirage created by admixture between modern humans and archaic "Palaeoafricans" diverging and admixing at different time depths. The palaeoanthropological record is quite clear that modern humans were not the only game in town for most of the 200 thousand years since modern humans first appeared in the continent's northeastern corner.

A handful or two of archaic genomes from Eurasia needs an ever-more-complex web of admixtures to make sense of; Africa will need no less, and -if morphological variability persistence is any criterion- a lot more.

Genome Research Published in Advance February 17, 2016, doi: 10.1101/gr.196634.115

Model-based analyses of whole-genome data reveal a complex evolutionary history involving archaic introgression in Central African Pygmies

PingHsun Hsieh et al.

Comparisons of whole-genome sequences from ancient and contemporary samples have pointed to several instances of archaic admixture through interbreeding between the ancestors of modern non-Africans and now extinct hominids such as Neanderthals and Denisovans. One implication of these findings is that some adaptive features in contemporary humans may have entered the population via gene flow with archaic forms in Eurasia. Within Africa, fossil evidence suggests that anatomically modern humans (AMH) and various archaic forms coexisted for much of the last 200,000 yr; however, the absence of ancient DNA in Africa has limited our ability to make a direct comparison between archaic and modern human genomes. Here, we use statistical inference based on high coverage whole-genome data (greater than 60×) from contemporary African Pygmy hunter-gatherers as an alternative means to study the evolutionary history of the genus Homo. Using whole-genome simulations that consider demographic histories that include both isolation and gene flow with neighboring farming populations, our inference method rejects the hypothesis that the ancestors of AMH were genetically isolated in Africa, thus providing the first whole genome-level evidence of African archaic admixture. Our inferences also suggest a complex human evolutionary history in Africa, which involves at least a single admixture event from an unknown archaic population into the ancestors of AMH, likely within the last 30,000 yr.


Genome Research Published in Advance February 17, 2016, doi: 10.1101/gr.192971.115

Whole-genome sequence analyses of Western Central African Pygmy hunter-gatherers reveal a complex demographic history and identify candidate genes under positive natural selection

PingHsun Hsieh et al.

African Pygmies practicing a mobile hunter-gatherer lifestyle are phenotypically and genetically diverged from other anatomically modern humans, and they likely experienced strong selective pressures due to their unique lifestyle in the Central African rainforest. To identify genomic targets of adaptation, we sequenced the genomes of four Biaka Pygmies from the Central African Republic and jointly analyzed these data with the genome sequences of three Baka Pygmies from Cameroon and nine Yoruba famers. To account for the complex demographic history of these populations that includes both isolation and gene flow, we fit models using the joint allele frequency spectrum and validated them using independent approaches. Our two best-fit models both suggest ancient divergence between the ancestors of the farmers and Pygmies, 90,000 or 150,000 yr ago. We also find that bidirectional asymmetric gene flow is statistically better supported than a single pulse of unidirectional gene flow from farmers to Pygmies, as previously suggested. We then applied complementary statistics to scan the genome for evidence of selective sweeps and polygenic selection. We found that conventional statistical outlier approaches were biased toward identifying candidates in regions of high mutation or low recombination rate. To avoid this bias, we assigned P-values for candidates using whole-genome simulations incorporating demography and variation in both recombination and mutation rates. We found that genes and gene sets involved in muscle development, bone synthesis, immunity, reproduction, cell signaling and development, and energy metabolism are likely to be targets of positive natural selection in Western African Pygmies or their recent ancestors.



Athena said...

I am trying to teach a course on human variation and adaptation at the moment, and I feel like the flow of archaic introgression and function papers has turned into a flood over the last six months. Trying to keep my lecture notes up to date is a nightmare - we only yesterday discussed the pygmy phenotype!

andrew said...

"I have little doubt that most if not all of the supposedly "old divergences" between African populations are a mirage created by admixture between modern humans and archaic "Palaeoafricans."

This doesn't ring true. Y-DNA A and B which are almost exclusively African are more basal, than the Y-DNA CF clade, which makes up the lion's share of non-African Y-DNA. mtDNA L0, L1 and L2 which are almost exclusively African are more basal than Y-DNA M and N which makes up virtually all non-African mtDNA. The peak level of admixture from any single species is small, and except for Neanderthals limited to relict first contact populations. The other reported statistical evidence of archaic admixture also involves a small percentage in an isolated Paleo-African population.

The bottleneck in mtDNA between the effective size of M and N v. the effective size of L3 (including M and N) as a whole, corroborates the fact that non-Africans should be less genetically diverse than Africans due to this founder effect. There is no archaeological trace of AMHs outside Africa prior to 125kya. The earliest genetic trace of AMH-Archaic hominin admixture from Altai Neanderthal DNA is 100kya, but there's evidence of modern humans in Africa back to 200kya and Africa is clearly where AMHs evolved. Ancient admixture is too small a factor to substantially distort this basic narrative.

African diversity may be elevated by Eurasian back migration to Europe that gives Africa a sliver of Eurasian diversity in addition to pre-existing African diversity. But, there is every reason to think that Africa is more genetically diverse to start with.

"A handful or two of archaic genomes from Eurasia needs an ever-more-complex web of admixtures to make sense of; Africa will need no less, and -if morphological variability persistence is any criterion- a lot more."

I think that we are very near the end of the road with Eurasian archaic admixture. I'd be very surprised to see more than one additional source of non-African admixture and any such admixture would have to be in a pretty small subset of genetically sampled populations, less than 1% ancestry, and/or from a population that has been population genetically isolated for a long time and not yet been genetically sampled (e.g. some population in an isolated valley in some Chinese mountain range that has been virtually untouched). Any other archaic sources are not just practically, but theoretically impossible to discover.

We have one confirmed but not described archaic source in African pygmies within the last 30kya. Previous studies have pointed to at least one more. If we could find more ancient African DNA, I agree that we might be able to find some additional ancient admixture that is older, and that perhaps 1-2 such additional finds might actually happen. (Note that the ancient DNA need not itself be archaic. It would suffice to find ancient AMH DNA that predates the additional archaic hominin admixture event or better yet, ancient AMH DNA immediately before and not long after the additional archaic hominin admixture event). But the window for that to happen is pretty much in parts of Africa that were inhabited by AMHs during the time frame of 40kya to 250kya and even then, we are talking about 3-4 archaic admixture events in all of African history, at least two of which are confined to small Paleo-African populations. Thus, the "Ewok village" of human origins won't get a lot more complex than it already is, and any new tweaks will be smaller in magnitude than what we have already discovered

Grogard said...
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Grogard said...
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Tom Bridgeland said...

A question for you better educated on this topic. I have seen estimates that pygmies diverged over 100,000 years ago from other modern African populations. But couldn't that early date be an artifact of this proposed archaic admixture? If any significant amount of 'other' genes entered the pygmy population relatively recently, wouldn't show up as if they had diverged far earlier than they really did?