Genetics of Pigmentation Diversity Nov 24, 2017 19:11:06 GMT
Post by Admin on Nov 24, 2017 19:11:06 GMT
Our analysis indicates that positive selection on pigmentation variants associated with depigmented hair, skin, and eyes was still ongoing after the time period represented by our archaeological population, 6,500–4,000 y ago. This finding suggests that either the selection pressures that initiated the selective sweep during the Late Pleistocene or early Holocene were still operative or that a new selective environment had arisen in which depigmentation was favored for a different reason.
The high selection coefficients estimated for pigmentation genes HERC2, SLC45A2, and TYR are best understood in the context of estimates obtained for other recently selected loci. Using spatially explicit simulation and approximate Bayesian computation, selection on the LCT -13,910*T allele—which is strongly associated with lactase persistence in Europeans and southern Asians—was inferred to fall in the range 0.0259–0.0795 and to have begun around 7,500 y ago in the region between the Balkans and central Europe (37). However, another simulation-based study incorporating latitudinal effects on selection resulted in a lower estimate of S (0.008–0.018) (38). The selective advantage of the G6PD A− and Med deficiency alleles conferring resistance to malaria have been estimated at 0.019–0.048 and 0.014–0.049, respectively, in regions where malaria is endemic (39). These alleles are estimated to have arisen ∼6,357 y ago (G6PD A−) and 3,330 y ago (G6PD Med) (39). Thus, the estimates of S for the three pigmentation genes examined in this study are comparable to those for the most strongly selected loci in the human genome.
Although these estimated selection coefficients are high, they are comparable to previous estimates for genes in the pigmentation complex. The selective sweeps favoring the SLC45A2 derived allele, as well as the derived alleles of SNPs in SLC24A5 and TYRP1, which are also implicated in the lightening of skin pigmentation, are estimated to have begun between 11,000 and 19,000 y ago, after the separation of the ancestors of modern Europeans and East Asians (the ages of the selective sweeps affecting HERC2 and TYR have not yet been estimated) (14, 40). Beleza et al. (14) recently estimated the coefficient of selection at the SLC45A2 locus to be 0.05 under a dominant model of inheritance and 0.04 under an additive model. Selection favoring the derived alleles of SNPs in SLC24A5 and TYRP1 was found to be similarly strong.
Estimating selection coefficients using the ancient DNA-based simulation approach presented here offers considerable advantages over traditional methods based on allele age and frequency estimates (1): Selection coefficients are estimated over a defined period; selection acting on standing variation can be accommodated; and our approach is insensitive to the frequently unaccounted for uncertainties associated with allele age estimation using molecular or recombination clocks. This latter advantage is likely to result in considerable improvements in precision. However, our approach does require the assumption of population continuity and will not provide direct estimates of when a selective sweep began.