Direct evidence for positive selection of skin, hair, and eye pigmentation in Europeans during the last 5,000 y

Abstract

Pigmentation is a polygenic trait encompassing some of the most visible phenotypic variation observed in humans. Here we present direct estimates of selection acting on functional alleles in three key genes known to be involved in human pigmentation pathways--HERC2, SLC45A2, and TYR--using allele frequency estimates from Eneolithic, Bronze Age, and modern Eastern European samples and forward simulations. Neutrality was overwhelmingly rejected for all alleles studied, with point estimates of selection ranging from around 2-10% per generation. Our results provide direct evidence that strong selection favoring lighter skin, hair, and eye pigmentation has been operating in European populations over the last 5,000 y.

Keywords: Eastern Europe; Neolithic/Bronze Age; ancient DNA; computer simulations; natural selection.

Fig. 1.

Probabilities of obtaining F_ST equal to or greater than that observed (0.00551) between 60 Eneolithic (ca. 6,500–5,000 y ago) and Bronze Age (ca. 5,000–4,000 y ago) samples from the Pontic–Caspian steppe, and a combined sample of 246 homologous modern sequences from the same geographic region, across a range of assumed ancestral population size combinations. Two phases of exponential growth were modeled, the first after the initial colonization of Europe 45,000 y ago, of assumed effective female population size N_UP (y axis), and ending when farming began in the region considered 7,000 y ago, when the assumed effective female population size was N_N (x axis), and the second leading up to the present, when the assumed effective female population size is 5,444,812. The initial colonizers of Europe were sampled from a constant ancestral African population of 5,000 effective females. Gray shaded areas indicate P values >0.05.

Fig. 2.

Two-tailed empirical P values for obtaining the observed (A) SLC45A2 G allele, (B) TYR A allele, and (C) HERC2 G allele frequency increase. P values were obtained by forward simulation of drift and natural selection across a range of assumed ancestral population sizes and selection coefficients, assuming exponential growth to a modern N_e of 4,845,710. The SLC45A2 rs16891982 G allele and the TYR rs1042602 A allele were assumed to be codominant. The HERC2 rs12913832 G allele was assumed to be recessive (values less than 0.01 are shaded gray).