The impact of natural selection on an ABCC11 SNP determining earwax type.

A nonsynonymous single nucleotide polymorphism (SNP), rs17822931-G/A (538G>A; Gly180Arg), in the ABCC11 gene determines human earwax type (i.e., wet or dry) and is one of most differentiated nonsynonymous SNPs between East Asian and African populations. A recent genome-wide scan for positive selection revealed that a genomic region spanning ABCC11, LONP2, and SIAH1 genes has been subjected to a selective sweep in East Asians. Considering the potential functional significance as well as the population differentiation of SNPs located in that region, rs17822931 is the most plausible candidate polymorphism to have undergone geographically restricted positive selection. In this study, we estimated the selection intensity or selection coefficient of rs17822931-A in East Asians by analyzing two microsatellite loci flanking rs17822931 in the African (HapMap-YRI) and East Asian (HapMap-JPT and HapMap-CHB) populations. Assuming a recessive selection model, a coalescent-based simulation approach suggested that the selection coefficient of rs17822931-A had been approximately 0.01 in the East Asian population, and a simulation experiment using a pseudo-sampling variable revealed that the mutation of rs17822931-A occurred 2006 generations (95% credible interval, 1,023-3,901 generations) ago. In addition, we show that absolute latitude is significantly associated with the allele frequency of rs17822931-A in Asian, Native American, and European populations, implying that the selective advantage of rs17822931-A is related to an adaptation to a cold climate. Our results provide a striking example of how local adaptation has played a significant role in the diversification of human traits.