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Reproductive longevity predicts mutation rates in primates

View ORCID ProfileGregg W.C. Thomas, Richard J. Wang, Arthi Puri, R. Alan Harris, Muthuswamy Raveendran, Daniel Hughes, Swetha Murali, Lawrence Williams, Harsha Doddapaneni, Donna Muzny, Richard Gibbs, Christian Abee, Mary R. Galinski, Kim C. Worley, Jeffrey Rogers, Predrag Radivojac, Matthew W. Hahn
doi: https://doi.org/10.1101/327627
Gregg W.C. Thomas
Indiana University;
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  • For correspondence: grthomas@indiana.edu
Richard J. Wang
Indiana University;
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Arthi Puri
Indiana University;
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R. Alan Harris
Baylor College of Medicine;
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Muthuswamy Raveendran
Baylor College of Medicine;
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Daniel Hughes
Baylor College of Medicine;
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Swetha Murali
Baylor College of Medicine;
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Lawrence Williams
University of Texas MD Anderson Cancer Center;
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Harsha Doddapaneni
Baylor College of Medicine;
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Donna Muzny
Baylor College of Medicine;
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Richard Gibbs
Baylor College of Medicine;
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Christian Abee
University of Texas MD Anderson Cancer Center;
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Mary R. Galinski
Emory University
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Kim C. Worley
Baylor College of Medicine;
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Jeffrey Rogers
Baylor College of Medicine;
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Predrag Radivojac
Indiana University;
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Matthew W. Hahn
Indiana University;
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Abstract

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. 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 by-product of their increased lifespan. Here, we deeply sequence the genomes of 30 owl monkeys (Aotus nancymaae) from 6 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 x 10-8 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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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  • Posted May 21, 2018.

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Reproductive longevity predicts mutation rates in primates
Gregg W.C. Thomas, Richard J. Wang, Arthi Puri, R. Alan Harris, Muthuswamy Raveendran, Daniel Hughes, Swetha Murali, Lawrence Williams, Harsha Doddapaneni, Donna Muzny, Richard Gibbs, Christian Abee, Mary R. Galinski, Kim C. Worley, Jeffrey Rogers, Predrag Radivojac, Matthew W. Hahn
bioRxiv 327627; doi: https://doi.org/10.1101/327627
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Reproductive longevity predicts mutation rates in primates
Gregg W.C. Thomas, Richard J. Wang, Arthi Puri, R. Alan Harris, Muthuswamy Raveendran, Daniel Hughes, Swetha Murali, Lawrence Williams, Harsha Doddapaneni, Donna Muzny, Richard Gibbs, Christian Abee, Mary R. Galinski, Kim C. Worley, Jeffrey Rogers, Predrag Radivojac, Matthew W. Hahn
bioRxiv 327627; doi: https://doi.org/10.1101/327627

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