Spontaneous germline mutations are the raw material on which evolution acts and knowledge of their frequency and genomic distribution is therefore crucial for understanding how evolution operates at both long and short timescales. At present, the rate and spectrum of de novo mutations have been directly characterized in only a few lineages, and it is therefore critical to examine a wide range of species to determine the generality of patterns that have been identified so far. Our study provides the first direct mutation rate estimate for strepsirrhine primates (i.e., the lemurs and lorises) which comprise nearly half of the primate clade. Using high-coverage linked-read sequencing of a family pedigree (n = 8) of gray mouse lemurs (Microcebus murinus), we estimate the mutation rate to be 1.64 x 10^-8 (95% CI: 1.41 x 10^-8 to 1.98 x 10^-8) mutations per basepair per generation. This estimate is higher than those for most previously characterized mammals, including other primates. Contrary to expectation, we found only a modest overrepresentation of mutations at CpG-sites and of paternal mutations. Comparing mutation rates across taxa, we show that expectations based on the drift barrier hypothesis are met at a broad phylogenetic scale but not within primates. Finally, we compared pedigree-based mutation rates with phylogenetically-based substitution rate estimates for mouse lemurs and six other primate lineages and found considerable differences between the two rate estimates. This finding has implications for divergence-time estimation and calls for further study.

Pedigree-based measurement of the de novo mutation rate in the gray mouse lemur reveals a high mutation rate, few mutations in CpG sites, and a weak sex bias