The germline mutational process in rhesus macaque and its implications for phylogenetic dating

Understanding the rate and pattern of germline mutations is of fundamental importance for understanding evolutionary processes. Here we analyzed 19 parent-offspring trios of rhesus macaques (Macaca mulatta) at high sequencing coverage of ca. 76X per individual, and estimated an average rate of 0.77 x 10-8 de novo mutations per site per generation (95 % CI: 0.69 x 10-8 - 0.85 x 10-8). By phasing 50 % of the mutations to parental origins, we found that the mutation rate is positively correlated with the paternal age. The paternal lineage contributed an average of 81 % of the de novo mutations, with a trend of an increasing male contribution for older fathers. About 3.5 % of de novo mutations were shared between siblings, with no parental bias, suggesting that they arose from early development (postzygotic) stages. Finally, the divergence times between closely related primates calculated based on the yearly mutation rate of rhesus macaque generally reconcile with divergence estimated with molecular clock methods, except for the Cercopithecidae/Hominoidea molecular divergence dated at 52 Mya using our new estimate of the yearly mutation rate.