Direct estimation of mutations in great apes reconciles phylogenetic dating

The human mutation rate per generation estimated from trio sequencing has revealed an almost linear relationship with the age of the father and the age of the mother, with fathers contributing about three times as many mutations per year as mothers. The yearly trio-based mutation rate estimate of around 0.43 × 10^-9 is markedly lower than previous indirect estimates of about 1 × 10^-9 per year from phylogenetic comparisons of the great apes calibrated by fossil evidence. This suggests either a slowdown in the accumulation of mutations per year in the human lineage over the past 10 million years or an inaccurate interpretation of the fossil record. Here we inferred de novo mutations in chimpanzee, gorilla, and orangutan parent-offspring trios. Extrapolating the relationship between the mutation rate and the age of parents from humans to these other great apes, we estimated that each species has higher mutation rates per year by factors of 1.50 ± 0.10, 1.51 ± 0.23, and 1.42 ± 0.22 for chimpanzee, gorilla, and orangutan, respectively, and by a factor of 1.48 ± 0.08 for the three species combined. These estimates suggest an appreciable slowdown in the yearly mutation rate in the human lineage that is likely to be recent as genome comparisons almost adhere to a molecular clock. If the nonhuman rates rather than the human rate are extrapolated over the phylogeny of the great apes, we estimate divergence and speciation times that are much more in line with the fossil record and the biogeography.