Natural selection also influences the extent to which allele frequencies differ between populations, not only through local selective pressures that drive alleles to different frequencies48,49, but also through local variation in the strength of purifying selection. We compared the distribution of population differentiation (as measured by FST, the proportion of total variation in allele frequency that is due to differences between populations) at non-synonymous SNPs and synonymous SNPs matched for allele frequency (Fig. 6b). We find a systematic bias for non-synonymous SNPs to show stronger differentiation than synonymous SNPs. Among SNPs showing high levels of differentiation there is a strong tendency for the derived allele to be at higher frequency in non-YRI populations. Among SNPs with FST>0.5 between CEU and YRI, in 79% and 75% of non-synonymous and synonymous variants, respectively, the derived allele is more common in CEU. Although this difference between non-synonymous and synonymous SNPs is not significant, among the eight exonic SNPs with FST>0.95, all are non-synonymous. We see no such bias towards increased MAF in CEU at high-differentiation SNPs, indicating that SNP ascertainment is unlikely to
