The relative contribution of mutation and purifying selection to transition bias has not been quantitatively assessed in mitochondrial protein genes. The observed transition/transversion (s/v) ratio is (μsPs)/(μvPv), where μs and μv denote mutation rate of transitions and transversions, respectively, andPs andPv denote fixation probabilities of transitions and transversions, respectively. Because selection against synonymous transitions can be assumed to be roughly equal to that against synonymous transversions,Ps/Pv ≈ 1 at fourfold degenerate sites, so that thes/v ratio at fourfold degenerate sites is approximately μs/μv, which is a measure of mutational contribution to transition bias. Similarly, thes/v ratio at nondegenerate sites is also an estimate of μs/μv if we assume that selection against nonsynonymous transitions is roughly equal to that against nonsynonymous transversions. In two mitochondrial genes, cytochrome oxidase subunit I (COI) and cytochromeb (cyt-b) in pocket gophers, thes/v ratio is about two at nondegenerate and fourfold degenerate sites for both the COI and the cyt-b genes. This implies that mutation contribution to transition bias is relatively small. In contrast, thes/v ratio is much greater at twofold degenerate sites, being 48 for COI and 40 for cyt-b. Given that the μs/μv ratio is about 2, thePs/Pv ratio at twofold degenerate sites must be on the order of 20 or greater. This suggests a great effect of purifying selection on transition bias in mitochondrial protein genes because transitions are synonymous and transversions are nonsynonymous at twofold degenerate sites in mammalian mitochondrial genes. We also found that nonsynonymous mutations at twofold degenerate sites are more neutral than nonsynonymous mutations at nondegenerate sites, and that the COI gene is subject to stronger purifying selection than is the cyt-b gene. A model is presented to integrate the effect of purifying selection, codon bias, DNA repair and GC content ons/v ratio of protein-coding genes.
Transition biasMitochondrial protein genePurifying selectionMolecular evolution