P ersp ective The Human Mutation Rate Is Increasing , Even As It Slows

Substitution rates vary between species, and many explanations regarding the causes of this variation have been proposed. Here we consider how new genomic data on the per-generation mutation rate impinge on proposed hypotheses for substitution rate variation in primates. We propose that the generation-time effect as it is usually understood cannot explain the observed rate variation, but instead that selection for decreased somatic mutation rates can. By considering the disparate causes underlying mutation rate changes in recent human history, we also show that the per-generation mutation rate is increasing even as the per-cell-division rate is decreasing.