Temporal dynamics of mildly deleterious nonsynonymous substitutions in mitochondrial gene sequences in rodents and moles.

Abstract

We have previously estimated the evolutionary rate (number of substitutions/site/million years) of mitochondrial cytochrome b gene (Cytb) sequences in rodents and moles to be about 0.11 at more recent divergence times of tens of thousands of years, and to decrease rapidly to about 0.03 at more distant divergence times. Because this time dependency is thought to be caused by the removal of mildly deleterious substitutions in later generations, we focused in this study on the abundance of nonsynonymous substitutions. We collected 23 haplogroups of Cytb with signals of late Quaternary population expansion events from rodents and moles and categorized them into three groups for comparison based on predicted expansion start time: 5,000-15,000 years ago (Group I), ca. 53,000 years ago (Group II) and 130,000-230,000 years ago (Group III). We counted the numbers of nonsynonymous and synonymous substitutions in all haplogroups. The rates of nonsynonymous substitutions were lowest in Groups II and III (0.08-0.22), whereas those in Group I varied markedly. We further classified Group I into two subgroups based on high (0.29-0.43) and low (0.09-0.20) nonsynonymous substitution rates, which were likely to be associated with the start of the expansion within 10,000 years and at around 15,000 years ago, respectively. The Group II and III networks had two- or three-step star-shaped structures and tended to exhibit frequent and less frequent nonsynonymous substitutions on exterior and interior branches, respectively. Based on temporal dynamics, nonsynonymous mitochondrial DNA (mtDNA) substitutions in small mammals accounted for at most 40% of all substitutions during the early evolutionary stage and then rapidly declined, dropping to approximately 15%. The results of this study provide a good explanation of the time-dependent trend in the mtDNA evolution rate predicted in previous work.