The Phase II HapMap also provides new insights into the forces acting on SNPs in coding regions. Effort was made to genotype as many known or putative non-synonymous SNPs as possible. Of the 56,789 non-synonymous SNPs identified in dbSNP release 125, attempts were made to genotype 36,777, which resulted in 17,427 that are QC+ in all three analysis panels and polymorphic. We selected only those SNPs for which ancestral allele information was available (approximately 90%). For comparison, we used patterns of variation at synonymous SNPs. As previously reported46,47, non-synonymous SNPs show an increase in frequency of rare variants and a slight decrease of common variants compared to synonymous SNPs, compatible with widespread purifying selection against non-synonymous mutations (Fig. 6a). In contrast, we find no excess of high-frequency derived non-synonymous mutations, as might be expected if positive selection were widespread.
