The timing of pigmentation lightening in Europeans

Abstract

The inverse correlation between skin pigmentation and latitude observed in human populations is thought to have been shaped by selective pressures favoring lighter skin to facilitate vitamin D synthesis in regions far from the equator. Several candidate genes for skin pigmentation have been shown to exhibit patterns of polymorphism that overlap the geospatial variation in skin color. However, little work has focused on estimating the time frame over which skin pigmentation has changed and on the intensity of selection acting on different pigmentation genes. To provide a temporal framework for the evolution of lighter pigmentation, we used forward Monte Carlo simulations coupled with a rejection sampling algorithm to estimate the time of onset of selective sweeps and selection coefficients at four genes associated with this trait in Europeans: KITLG, TYRP1, SLC24A5, and SLC45A2. Using compound haplotype systems consisting of rapidly evolving microsatellites linked to one single-nucleotide polymorphism in each gene, we estimate that the onset of the sweep shared by Europeans and East Asians at KITLG occurred approximately 30,000 years ago, after the out-of-Africa migration, whereas the selective sweeps for the European-specific alleles at TYRP1, SLC24A5, and SLC45A2 started much later, within the last 11,000-19,000 years, well after the first migrations of modern humans into Europe. We suggest that these patterns were influenced by recent increases in size of human populations, which favored the accumulation of advantageous variants at different loci.

Fig. 1.

Schematic representation of the genetic intervals including tag-SNPs and microsatellites used to characterize HD. The approximate locations of pigmentation genes are indicated by black arrows. The full characterization of each tag-SNP and microsatellite is reported in supplementary table S1, Supplementary Material online. (A) TYRP1; (B) SLC24A5; (C) SLC45A2; and (D) KITLG.

Fig. 2.

Median-joining networks representing the relationships between compound SNP/microsatellite haplotypes associated with different pigmentation genes. Ancestral (black) and derived (yellow) lineages from the pooled sample of European, East Asian, and African populations are shown. Each circle represents a different haplotype. The area of the circles is proportional to the frequency of the haplotype in the populations. The arrows point to the putative ancestral haplotype of each derived lineage. (A) TYRP1; (B) SLC24A5; (C) SLC45A2; and (D) KITLG.

Fig. 3.

Biplots of the posterior densities of the times of onset of selective sweeps in generations (x axes) and selection coefficients (y axes), at each of four tag SNPs at the KITLG (A–D), TYRP1 (E,F), SLC24A5 (G,H), and SLC45A2 (I,J) loci, assuming dominant (A, C, E, G, I) and additive (B, D, F, H, J) models of selection. The mode is marked by a black dot. Shades of gray with decreasing intensity indicate 50, 75, 90, and 95% HDR.