Neanderthal introgression in the ancient DNA age

Over the past ten years or so the idea of “adaptive introgression” in the human context has gone from seeming ludicrous to banal. When I first began entertaining this idea in 2006 some commenters literally heckled me, because the idea of admixture with Neanderthals seemed so ludicrous. Then, in 2010 the maturation of the field of ancient human DNA confirmed that it was likely non-Africans had Neanderthal admixture. Over the next few years, specific instances of introgression were discovered (e.g., EPAS1 from a Denisova-relative).

Today the whole landscape of adaptive introgression from other lineages is now being mapped. An open access paper in Molecular Biology and Evolution, Disentangling Immediate Adaptive Introgression from Selection on Standing Introgressed Variation in Humans, examines the distinction between the immediate sweep of an introgressed allele after admixture, and later selection on alleles which are segregating neutrally within the absorbing population.

The authors developed a statistic which detected “immediate adaptive introgression (iAI).” Instances where alleles increased in frequency immediately after the admixture in the modern human background from Neanderthals (or possibly other archaics?).

One interesting gene was LYPD6B. This seems to have been subject to selection immediately, and it’s widely distributed in modern non-Africans. This locus controls “cholinergic signaling in the brain” and the authors suggest that the “results suggest that selection on this introgressed haplotype may have been due to beneficial behavioral and/or physiological traits.” The other possible cases of iAI seem mostly involved immune response, not entirely surprising.

But perhaps the bigger issue is that there may be a lot of selection on segregating variants that came in from Neanderthals. That is, introgression may be more important for selection on standing variation. This is is probably the dominant mode of adaptation in humans in any case. Think of it is portfolio diversification.

Speaking of variation, there’s a paper in the works which suggests that admixture with Neanderthals replenished some of the genetic diversity that the Out-of-Africa modern lineage lost:

“They left many beneficial variants behind in Africa,” says evolutionary genomicist Tony Capra of Vanderbilt University in Nashville, who reported the results. “Interbreeding with Neandertals provided an opportunity to get back some of those variants, albeit with many potentially weakly deleterious Neandertal alleles as well.”