Reproductive Longevity Predicts Mutation Rates in Primates.

Area of Science:

• Evolutionary biology
• Genomics
• Molecular evolution

Background:

• Mutation rates vary significantly across species, with larger organisms exhibiting higher per-generation rates.
• Existing hypotheses often focus on physiological or population-genetic constraints on the molecular machinery.
• Alternatively, increased germline cell division due to longer lifespans and larger body size in multicellular eukaryotes may increase mutation accumulation.

Purpose of the Study:

• To investigate the primary drivers of de novo mutation rates in owl monkeys (Aotus nancymaae).
• To compare the mutation rate of owl monkeys to that of humans and other primates.
• To develop and test a model explaining interspecies mutation rate variation based on life history traits.

Main Methods:

• Deep whole-genome sequencing of 30 owl monkeys from six multi-generation pedigrees.
• Analysis of de novo mutations to determine the mutation rate per site per generation.
• Development of a reproductive longevity model to predict mutation rates.

Main Results:

• Owl monkeys exhibit an average mutation rate of 0.81 × 10^-8 per site per generation, approximately 32% lower than humans.
• Paternal age was identified as the major determinant of de novo mutation numbers in owl monkeys.
• The reproductive longevity model accurately predicted owl monkey mutation rates and explained interspecies variation in primates, including humans.

Conclusions:

• Variation in life history traits, such as lifespan and reproductive patterns, can sufficiently explain differences in per-generation mutation rates among primates.
• The findings challenge hypotheses solely focused on molecular machinery constraints and highlight the role of organismal biology.
• The model suggests that life history variation may account for mutation rate differences across a broad range of multicellular organisms.