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De novo mutations in domestic cat are consistent with an effect of reproductive longevity on both the rate and spectrum of mutations

View ORCID ProfileRichard J. Wang, Muthuswamy Raveendran, R. Alan Harris, William J. Murphy, Leslie A. Lyons, Jeffrey Rogers, View ORCID ProfileMatthew W. Hahn
doi: https://doi.org/10.1101/2021.04.06.438608
Richard J. Wang
1Department of Biology, Indiana University, Bloomington, IN
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  • For correspondence: rjwang@indiana.edu
Muthuswamy Raveendran
2Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX
3Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX
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R. Alan Harris
2Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX
3Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX
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William J. Murphy
4Veterinary Integrative Biosciences, Texas A&M University, College Station, TX
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Leslie A. Lyons
5Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO
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Jeffrey Rogers
2Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX
3Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX
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Matthew W. Hahn
1Department of Biology, Indiana University, Bloomington, IN
6Department of Computer Science, Indiana University, Bloomington, IN
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Abstract

The mutation rate is a fundamental evolutionary parameter with direct and appreciable effects on the health and function of individuals. Here, we examine this important parameter in the domestic cat, a beloved companion animal as well as a valuable biomedical model. We estimate a mutation rate of 0.86 × 10−8 per bp per generation for the domestic cat (at an average age of 3.8 years). We find evidence for a strong paternal age effect, with more mutations transmitted by older sires. Our analyses suggest that the cat and the human have accrued similar numbers of mutations in the germline before reaching sexual maturity. The per-generation mutation rate in the cat is slightly lower than what has been observed in humans, but consistent with the shorter generation time in the cat. Using a model of reproductive longevity, which takes into account differences in the reproductive age and time to sexual maturity, we are able to explain much of the difference in per-generation rates between species. We further apply our reproductive longevity model in a novel analysis of mutation spectra and find that the spectrum for the cat resembles the human mutation spectrum at a younger age of reproduction. Together, these results implicate changes in life-history as a driver of mutation rate evolution between species. As the first direct observation of the paternal age effect outside of primates, our results also suggest a phenomenon that may be universal among mammals.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
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 April 06, 2021.
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De novo mutations in domestic cat are consistent with an effect of reproductive longevity on both the rate and spectrum of mutations
Richard J. Wang, Muthuswamy Raveendran, R. Alan Harris, William J. Murphy, Leslie A. Lyons, Jeffrey Rogers, Matthew W. Hahn
bioRxiv 2021.04.06.438608; doi: https://doi.org/10.1101/2021.04.06.438608
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De novo mutations in domestic cat are consistent with an effect of reproductive longevity on both the rate and spectrum of mutations
Richard J. Wang, Muthuswamy Raveendran, R. Alan Harris, William J. Murphy, Leslie A. Lyons, Jeffrey Rogers, Matthew W. Hahn
bioRxiv 2021.04.06.438608; doi: https://doi.org/10.1101/2021.04.06.438608

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