Early last year an ancient genomics paper came out with the title Derived immune and ancestral pigmentation alleles in a 7,000-year-old Mesolithic European
. The point here is that light pigmentation associated alleles common in Europeans seem to be relatively new derived mutations from the ancestral state, associated with Africans. An Ewen Callaway write up
highlighted the fact that one of the inferences made from these genomes is that these hunter-gatherers had light eyes (blue) and dark(er) skin. At the time I pointed out to Callaway on Twitter that we need to be careful here, as ancient Europeans may have had different variants, and these traits are not monogenic but exhibit dependencies on multiple loci. In light of my post below Graham Coop
suggested a similar issue, that there could have been convergence. In other words, just because modern Europeans have particular derived alleles which confer a particular trait, it does not entail that ancient peoples who lived in Europe had to have the same alleles to confer the same phenotype. Alicia Martin
observed that OCA2 is a locus where fast evolution occurred in both East Asians and West Eurasians (especially Europeans), but at different SNPs. In other words, the same gene is modified, but the mutational event is distinct.
Pigmentation in humans seems to be a trait we have a pretty good grasp of. Because most of the genetic variation between populations seems to be localized at relatively large effect loci GWAS has been good at picking up the signals. Tests of selection which look at haplotype structure also detect these loci because many of them seem to have swept up in frequency relatively recently. This is consonant with what ancient DNA is telling us, as a substantial proportion of modern European ancestry does derive from peoples who have been resident at high latitudes for tens of thousands of years, but new variants, possibly from the Middle East or elsewhere, have increased in frequency within this admixed populations (in South Asia the same pattern is evident, as the Ancestral North Indians likely introduced West Eurasian variants into the hybrid daughter populations).
But let’s think through some of the implications of the alternative scenarios. One model is implicitly the dominant one, that the modern skin lightening alleles which are derived in contemporary populations are due to new pressures for de-pigmentation. Though some de-pigmentation likely occurred early on, perhaps even in Neandertals, the full suite is recent. Another model is that there were other variants segregating in the older populations, and that new populations brought new variants which swept to fixation. My question is simple: if the indigenous populations of Europe were already relatively light skinned whey did the new alleles rise in frequency so rapidly?
Let’s unpack what I’m getting at. OCA2 and SLC24A5 are two loci implicated in de-pigmentation in Europeans. The regions around the selective events are highly homogenized so that there’s a long haplotype around them. This means that the causal variant was targeted by such strong selection that the flanking regions of the genome were swept upward in frequency faster than recombination could break apart the association. SLC24A5 in particular seems to have been under very strong selection, to the point where almost all variation has been purged from European populations at this locus. In India SLC24A5 is also at a higher frequency than might be predicted by simple contribution of ANI ancestry. The issue that I’m getting at, assuming that modern continental populations such as Europeans are admixed, is why these skin lightening alleles swept to frequency so rapidly and in the case of SLC24A5 nearly to fixation. It’s framed by the analysis presented by this paper, Parallel Adaptation: One or Many Waves of Advance of an Advantageous Allele?:
Models for detecting the effect of adaptation on population genomic diversity are often predicated on a single newly arisen mutation sweeping rapidly to fixation. However, a population can also adapt to a new environment by multiple mutations of similar phenotypic effect that arise in parallel, at the same locus or different loci. These mutations can each quickly reach intermediate frequency, preventing any single one from rapidly sweeping to fixation globally, leading to a “soft” sweep in the population. Here we study various models of parallel mutation in a continuous, geographically spread population adapting to a global selection pressure. The slow geographic spread of a selected allele due to limited dispersal can allow other selected alleles to arise and start to spread elsewhere in the species range. When these different selected alleles meet, their spread can slow dramatically and so initially form a geographic patchwork, a random tessellation, which could be mistaken for a signal of local adaptation. This spatial tessellation will dissipate over time due to mixing by migration, leaving a set of partial sweeps within the global population. We show that the spatial tessellation initially formed by mutational types is closely connected to Poisson process models of crystallization, which we extend. We find that the probability of parallel mutation and the spatial scale on which parallel mutation occurs are captured by a single compound parameter, a characteristic length, which reflects the expected distance a spreading allele travels before it encounters a different spreading allele. This characteristic length depends on the mutation rate, the dispersal parameter, the effective local density of individuals, and to a much lesser extent the strength of selection. While our knowledge of these parameters is poor, we argue that even in widely dispersing species, such parallel geographic sweeps may be surprisingly common. Thus, we predict that as more data become available, many more examples of intraspecies parallel adaptation will be uncovered.
Basically, if the ancient North Eurasian populations had lighter skin due to their own alleles, why are the new light skin alleles sweeping up in frequency so strongly after admixture? (for Europeans, I’m thinking SLC45A2 and SLC24A5 in particular). Perhaps the selective sweeps were not driven by light skin at all? Or, perhaps the ancient North Eurasians didn’t have their own variants.
Addendum: The 2007 Neandertal red hair paper offers up a possible solution toward phenotype reconstruction: test the ancient genetic variants in cell lines to check for expression.