ICCFGG program 2022

POSTER ABSTRACTS

#66 De novo mutation rate in the domestic cat Richard J Wang , Muthuswamy Raveendran, R Alan Harris, William J Murphy, Leslie A Lyons, Jeffrey Rogers, and Matthew W Hahn rjwang@iu.edu The mutation rate is a fundamental evolutionary parameter with direct and appreciable effects on the health and function of individuals. We examine this important parameter in the domestic cat, a beloved companion animal as well as a valuable biomedical model. Using whole-genome sequence data from 11 trios of the domestic cat, we estimate a mutation rate of 0.86×10 −8 per bp per gener- ation (at an average parental age of 3.8 years). This per-generation mutation rate in the cat is 28% lower than what has been observed in humans, but is consistent with the shorter generation time in the cat. We also find evidence for a significant 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. Using a model of cat and human repro- ductive longevity, 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. Our findings also have important implications for reconstructing the evolutionary history of cats, as well as for captive breeding management.

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