Fig. 1.

Mutational burden in class A GPCRs. (A–D) The substitution rate per position is shown as histograms. Nonsynonymous substitution rate for olfactory and nonolfactory GPCRs in pan-cancer, and for olfactory in 1000 Genome Project are significantly right-shifted compared to that of synonymous substitution. In contrast, the synonymous substitution rate is higher than nonsynonymous for nonolfactory GPCRs in the 1000 Genome Project. Kolmogorov–Smirnov distances are (A) 0.725, (B) 0.662, (C) 0.201, and (D) 0.350, and, for all four distribution, P values are less than 0.0001. (E and F) The z score of nonsynonymous substitutions at cognate residue positions. Positions of residues discussed in the text are indicated.