Characterization of de novo germline mutations suggests a strong male mutation bias in coppery titi monkeys ( <i>Plecturocebus cupreus</i> )

Although recent advances in genomics have enabled the high-resolution study of whole genomes, our understanding of one of the key evolutionary processes, mutation, still remains limited. In primates specifically, studies have largely focused on humans and their closest evolutionary relatives, the great apes, as well as a handful of species of biomedical or conservation interest. Yet, as mutation rates vary across genomic regions, individuals, and species, a greater understanding of the underlying evolutionary dynamics at play will ultimately be illuminated by not only additional sampling across the order but also by a greater depth of sampling within species. To address these needs, we here present the first population-scale genomic resources for the coppery titi monkey (Plecturocebus cupreus)-a platyrrhine of considerable biomedical interest for both social behavior and neurobiology. Deep whole-genome sequencing of 15 parent-offspring trios, together with a computational de novo mutation detection pipeline based on pan-genome graphs, has provided a detailed picture of the sex-averaged mutation rate-0.63 × 10-8 (95% CI: 0.43 × 10-8-0.90 × 10-8) per site per generation-as well as the effects of both sex and parental age on underlying rates, demonstrating a significant paternal age effect. Coppery titi monkey males exhibit long reproductive lifespans, afforded by long-term pair bonding in the species' monogamous mating system, and our results have demonstrated that individuals reproducing later in life exhibit one of the strongest male mutation biases observed in any non-human primate studied to date. Taken together, this study thus provides an important piece of the puzzle for better comprehending the mutational landscape across primates.