To investigate selective constraint acting on synonymous variants, we calculated the correlation between the derived allele frequency (DAF) of synonymous variants and their corresponding change in the relative adaptiveness value, or w score (24). The w score summarizes information about selective constraints on the efficiency of codon-anticodon coupling and the number of tRNA gene copies in the genome. Negative values indicate synonymous variants that may decrease translational efficiency or accuracy. We found a weak but significant positive correlation between DAF and change in w score (r = 0.03; P < 10−16), consistent with the action of purifying selection (Fig. 3D).
