Recovering signals of “ghost archaic introgression” in African populations

Under the umbrella of gene-environment interactions, these GEITP pages often discuss evolution of human migration across the planet. This particular article was submitted to me by a GEITP-er who felt “ghost” in the title was “intriguing”. 😊 Admixture (i.e. presence of DNA in an individual from a distantly-related population or species, as a result of interbreeding between populations or species that have been reproductively isolated and genetically differentiated) has been a dominant force in shaping patterns of genetic variation in human populations. This topic is relevant today in “personalized medicine”, where we see ethnic differences in response to drugs or environmental toxicants (that often reflect variation in metabolism, receptors and transporters).

Comparisons of genome sequences from archaic hominins, to those from present-day humans, have documented multiple interbreeding events — including gene flow from Neanderthals into ancestors of all non-Africans (as well as back into Africans), from Denisovans into Oceanians and eastern non-Africans, and from early modern humans into Neanderthals. However, the sparse fossil record and difficulty in obtaining ancient DNA — have made it challenging to dissect the contribution of archaic hominins to genetic diversity within Africa.

Authors [see attached article] leveraged whole-genome sequence (WGS) data from present-day West African populations, and from archaic hominins to compute statistics that are sensitive to introgression (i.e. the transfer of genetic information from one species or subpopulation to another, as a result of hybridization between them and repeated backcrossing) in the history of these populations. Authors tabulated the distribution of frequencies of derived alleles (where a derived allele, or single copy of any gene, is determined, relative to an inferred human ancestor allele) in the analyzed African populations at single-nucleotide variants (SNVs) — for which a randomly sampled allele from an archaic individual was observed to also be derived.

Theory predicts that this conditional site frequency spectrum (CSFS) is expected to be uniformly distributed — when alleles are neutrally evolving under a demographic model in which the ancestor of modern and archaic humans, assumed to be at “mutation-drift equilibrium”, diverged — with no subsequent gene flow between the two groups. This expectation is also robust to assumptions about changes in population sizes in the history of modern human or archaic populations. Moreover, authors show that this expectation holds — even when there is population structure or gene flow in the history of the archaic population.

Authors [see attached article] provide complementary lines of evidence to support archaic introgression into four West African populations. The authors’ analyses of CSFS indicate that these populations represent 2% to 19% of their genetic ancestry from an archaic population — that diverged before the split of Neanderthal and modern human. Using a method that can identify segments of archaic ancestry (without the need for reference archaic genomes), authors constructed genome-wide maps of archaic ancestry in the Yoruba and the Mende (African) populations. Analyses of these maps reveal segments of archaic ancestry at high frequency that represent potential targets of adaptive introgression. These data reveal the substantial contribution of archaic ancestry in shaping the gene pool of present-day West African populations.


Sci Advanc (Nature) 12 Feb 2020; 6: eaax5097

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