Variation in the molecular clock of primates

Much of our understanding of the chronology of human evolution relies on a fixed "molecular clock"; that is, a constant rate of substitutions per unit time. To evaluate the validity of this assumption, we analyze whole-genome sequences from 10 primate species. We find that there is substantial variation in the molecular clock between apes and monkeys and that rates even differ within hominines. Importantly, not all mutation types behave similarly; notably, transitions at CpG sites exhibit a more clocklike behavior than other substitutions, presumably because of their nonreplicative origin. Thus, the mutation spectra, and not just the overall substitution rates, are changing across primates. This finding suggests that events in primate evolution are most reliably dated using CpG transitions.