De Novo Mutation Rate Estimation in Wolves of Known Pedigree

Koch, Evan; Schweizer, Rena M.; Schweizer, Teia M.; Stahler, Daniel R.; Smith, Douglas W.; Wayne, Robert K.; Novembre, John

doi:10.1093/molbev/msz159

Cited by 62 publications

(96 citation statements)

References 62 publications

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“…Interestingly, our estimate of the per-generation mutation rate in the cat is nearly double the estimate in the wolf (Canis lupus), another member of the order Carnivora, at 0.45 × 10 -8 per bp (Koch et al 2019). Given the relatively similar age at reproduction for the wolves used in this study (mean: 3.1 y), and the consistency of our estimates with a reproductive longevity model, we are not sure where the discrepancy in these estimates lies.…”

Section: Discussionmentioning

confidence: 56%

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

Wang

Raveendran

et al. 2021

Preprint

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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.

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Section: Discussionmentioning

confidence: 56%

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

Wang

Raveendran

et al. 2021

Preprint

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“…This approach has been applied to humans in numerous studies, confirming that most mutations are paternal in origin and revealing a strong, linear paternal age effect as well as a weaker maternal age effect on the number of DNMs [ 17 – 19 ]. Analogous data have also been collected in much smaller numbers of trios from other mammals, including mice [ 4 ], wolves [ 20 ], cattle [ 2 ], and primates (see Table 1 ).…”

Section: Introductionmentioning

confidence: 99%

A comparison of humans and baboons suggests germline mutation rates do not track cell divisions

et al. 2020

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In humans, most germline mutations are inherited from the father. This observation has been widely interpreted as reflecting the replication errors that accrue during spermatogenesis. If so, the male bias in mutation should be substantially lower in a closely related species with similar rates of spermatogonial stem cell divisions but a shorter mean age of reproduction. To test this hypothesis, we resequenced two 3-4 generation nuclear families (totaling 29 individuals) of olive baboons (Papio anubis), who reproduce at approximately 10 years of age on average, and analyzed the data in parallel with three 3-generation human pedigrees (26 individuals). We estimated a mutation rate per generation in baboons of 0.57×10 −8 per base pair, approximately half that of humans. Strikingly, however, the degree of male bias in germline mutations is approximately 4:1, similar to that of humans-indeed, a similar male bias is seen across mammals that reproduce months, years, or decades after birth. These results mirror the finding in humans that the male mutation bias is stable with parental ages and cast further doubt on the assumption that germline mutations track cell divisions. Our mutation rate estimates for baboons raise a further puzzle, suggesting a divergence time between apes and Old World monkeys of 65 million years, too old to be consistent with the fossil record; reconciling them now requires not only a slowdown of the mutation rate per generation in humans but also in baboons.

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“…Studies that used genomic sequences from ancient wolf and dog samples have estimated even lower mutation rates of 4 × 10 −9 [ 45 ] and 3–4.5 × 10 −9 mutations/bp/generation [ 46 ] (both excluding CG substitutions). A recent study using wolf parent–offspring trios provides concordant rates, with a point estimate of 4.5 × 10 −9 (2.6–7.1 × 10 −9 ) [ 55 ]. In this work, we considered two combinations of mutation rate and generation time: (i) 4 × 10 −9 mutations/bp/generation and 4.5 years/generation and (ii) 1 × 10 −8 mutations/bp/generation and 3 years/generation.…”

Section: Discussionmentioning

confidence: 86%

Genomic evidence for the Old divergence of Southern European wolf populations

et al. 2020

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The grey wolf ( Canis lupus ) is one of the most widely distributed mammals in which a variety of distinct populations have been described. However, given their currently fragmented distribution and recent history of human-induced population decline, little is known about the events that led to their differentiation. Based on the analysis of whole canid genomes, we examined the divergence times between Southern European wolf populations and their ancient demographic history. We found that all present-day Eurasian wolves share a common ancestor ca 36 000 years ago, supporting the hypothesis that all extant wolves derive from a single population that subsequently expanded after the Last Glacial Maximum. We also estimated that the currently isolated European populations of the Iberian Peninsula, Italy and the Dinarics-Balkans diverged very closely in time, ca 10 500 years ago, and maintained negligible gene flow ever since. This indicates that the current genetic and morphological distinctiveness of Iberian and Italian wolves can be attributed to their isolation dating back to the end of the Pleistocene, predating the recent human-induced extinction of wolves in Central Europe by several millennia.

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De Novo Mutation Rate Estimation in Wolves of Known Pedigree

Cited by 62 publications

References 62 publications

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

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

A comparison of humans and baboons suggests germline mutation rates do not track cell divisions

Genomic evidence for the Old divergence of Southern European wolf populations

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