Selection for pigmentation in Khoisan?

In the recent paper, Reconstructing Prehistoric African Population Structure, there was a section natural selection. Since my post on the paper was already very long I didn’t address this dynamic.

But now I want to highlight this section:

The functional category that displays the most extreme allele frequency differentiation between present day San and ancient southern Africans is ‘‘response to radiation’’ (Z = 3.3 compared to the genome-wide average). To control for the possibility that genes in this category show an inflated allele frequency differentiation in general, we computed the same statistic for the Mbuti central African rainforest hunter-gatherer group but found no evidence for selection affecting the response to radiation category.

We speculate that the signal for selection in the response to radiation category in the San could be due to exposure to sunlight associated with the life of the Khomani and Juj’hoan North people in the Kalahari Basin, which has become a refuge for hunter-gatherer populations in the last millenia due to encroachment by pastoralist and agriculturalist groups.

I’m a bit puzzled here, because the implication seems to be that the San populations are darker than they were in the past. And yet earlier this summer I saw a talk which strongly suggested that there was a selection in modern Bushman populations for the derived variant of SLC24A5, presumably introduced through admixture from East African populations with Eurasian admixture.

In comparison to their neighbors the San are quite light-skinned, so it’s a reasonable supposition that they have been subject to natural selection recently. The Hadza, in contrast, seem to have the same complexion as their Bantu neighbors.

So what’s point of demographic models which leave you scratching your head


There’s a new paper on Tibetan adaptation to high altitudes, Evolutionary history of Tibetans inferred from whole-genome sequencing. The focus of the paper is on the fact that more genes than have previously been analyzed seem to be the targets of natural selection. And I buy most of their analyses (not sure about the estimate of Denisovan ancestry being 0.4%…these sorts of things can be tricky).

But they fancy it up with a ∂a∂i model of population history, as well as using MSMC to account for gene flow. I don’t understand why they didn’t use something simpler like TreeMix, which can also handle more complex models. I guess because they wanted to focus on only a few populations?

Years ago I asked the developer of MSMC, Stephan Schiffels, if assuming an admixed population is not admixed might cause weird inferences. Why yes, it would. For example, admixed populations might show higher effective population since they’re pooling the histories of two separate populations. As for ∂a∂i, the model above leaves me literally scratching my head.

…predicted that the initial divergence between Han and Tibetan was much earlier, at 54kya (bootstrap 95% C.I 44 kya to 58 kya). However, for the first 45ky, the two populations maintained substantial gene flow (6.8×10-4 and 9.0×10-4 per generation per chromosome). After 9.4 kya (bootstrap 95% C.I 8.6 kya to 11.2 kya), the gene flow rate dramatically dropped (1.3×10-11 and 4×10-7 per generation per chromosome), which is consistent with the estimate from MSMC.

Mystifying. The separation between Chinese and Tibetans is pretty much immediately after modern humans arrive in East Asia. Then there’s a lot of reciprocal gene flow…which ends during the Holocene.

We’re being told here that there are two populations which persisted in some form for ~45,000 years. Is this believable? That these two populations maintained some sort of continuity, and, remained in close proximity to engage in gene flow. And then ~10,000 years ago the ancestors of the Tibetans separated from the ancestors of the modern Han Chinese.

The latter scenario I can imagine. It’s this ~45,000 year dance I’m confused by. If there is substantial gene flow between the two groups why did they keep enough distinctive drift to be separate populations?

With what we know about ancient DNA from Europe if we posited such a model for that continent we’d be way off. There’s been too many population turnovers. Is East Asia different? I’m moderately skeptical of that. I think perhaps researchers should be very aware of the limitations of ∂a∂i when it comes to fine-grained population genomic analyses.

Note: This is a cool paper, and this small section is not entirely relevant. Which is why I’m confused about it since it seems the weakest part of the analysis in terms of originality, and the least believable.