Reproductive Longevity Predicts Mutation Rates in Primates.

TitleReproductive Longevity Predicts Mutation Rates in Primates.
Publication TypeJournal Article
Year of Publication2018
AuthorsThomas, GWC, Wang, RJ, Puri, A, Harris, RA, Raveendran, M, Hughes, DST, Murali, SC, Williams, LE, Doddapaneni, H, Muzny, DM, Gibbs, RA, Abee, CR, Galinski, MR, Worley, KC, Rogers, J, Radivojac, P, Hahn, MW
JournalCurr Biol
Date Published2018 Oct 08
KeywordsAnimals, Aotidae, Genetic Fitness, Genetics, Population, Genome, Humans, Longevity, Mutation, Mutation Rate, Pedigree, Population Density, Primates, Reproduction

Mutation rates vary between species across several orders of magnitude, with larger organisms having the highest per-generation mutation rates. Hypotheses for this pattern typically invoke physiological or population-genetic constraints imposed on the molecular machinery preventing mutations [1]. However, continuing germline cell division in multicellular eukaryotes means that organisms with longer generation times and of larger size will leave more mutations to their offspring simply as a byproduct of their increased lifespan [2, 3]. Here, we deeply sequence the genomes of 30 owl monkeys (Aotus nancymaae) from six multi-generation pedigrees to demonstrate that paternal age is the major factor determining the number of de novo mutations in this species. We find that owl monkeys have an average mutation rate of 0.81 × 10 per site per generation, roughly 32% lower than the estimate in humans. Based on a simple model of reproductive longevity that does not require any changes to the mutational machinery, we show that this is the expected mutation rate in owl monkeys. We further demonstrate that our model predicts species-specific mutation rates in other primates, including study-specific mutation rates in humans based on the average paternal age. Our results suggest that variation in life history traits alone can explain variation in the per-generation mutation rate among primates, and perhaps among a wide range of multicellular organisms.

Alternate JournalCurr Biol
PubMed ID30270182
PubMed Central IDPMC6177314
Grant ListHHSN272201200031C / AI / NIAID NIH HHS / United States
P40 OD010938 / OD / NIH HHS / United States

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