Evolution of the mutation rate across primates

Chintalapati, Manjusha; Moorjani, Priya

doi:10.1016/j.gde.2020.05.028

Cited by 46 publications

(55 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since generation times vary among species, direct estimates of the mutation rate across species are difficult to compare. Nevertheless, current data suggest at least a twofold range of mutation rates among primates (Chintalapati and Moorjani 2020). In almost all primate species studied to date, paternal age has an effect on the number of inherited mutations (Kong et al 2012;Venn et al 2014;Goldmann et al 2016;Thomas et al 2018;Besenbacher et al 2019;Bergeron et al 2020;Wang et al 2020).…”

Section: Introductionmentioning

confidence: 75%

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

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 75%

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

View full text Add to dashboard Cite

show abstract

“…An alternative to the phylogenetic estimation of u is to rely on high-throughput sequencing of pedigrees. As of yet, such estimates are available only for 7 primates (Chintalapati & Moorjani, 2020), but this is likely to change in the future. For these 7 species, the phylogenetic estimates obtained here are higher than pedigree-based estimates, thus in line with previous observations.…”

Section: Discussionmentioning

confidence: 99%

“…For these 7 species, the phylogenetic estimates obtained here are higher than pedigree-based estimates, thus in line with previous observations. The reasons for this discrepancy are not yet well-understood (Scally & Durbin, 2012; Ségurel et al , 2014; Chintalapati & Moorjani, 2020). Interestingly, accounting for coalescence in the ancestral populations contributes a lot to making phylogenetic estimates closer to those obtained in the same species by sequencing pedigrees, although not entirely.…”

Section: Discussionmentioning

confidence: 99%

Reconstructing the history of variation in effective population size along phylogenies

Brevet

Lartillot

2019

Preprint

View full text Add to dashboard Cite

The nearly-neutral theory predicts specific relations between effective population size (N e ), and patterns of divergence and polymorphism, which depend on the shape of the distribution of fitness effects (DFE) of new mutations. However, testing these relations is not straightforward since N e is difficult to estimate in practice. For that reason, indirect proxies for N e have often been used to test the nearly-neutral theory, although with mixed results. Here, we introduce an integrative comparative framework allowing for an explicit reconstruction of the phylogenetic history of N e , thus leading to a quantitative test of the nearly-neutral theory and an independent estimation of the shape parameter of the DFE. We applied our method to primates, for which the nearlyneutral predictions were mostly verified. Estimates of the shape parameter were compatible with independent measures based on site frequency spectra. The reconstructed history of N e in primates seems consistent with current knowledge and shows a clear phylogenetic structure at the superfamily level. Altogether, our integrative framework provides a quantitative assessment of the role of N e in modulating patterns of genetic variation, while giving a synthetic picture of the long-term trends in N e variation across a group of species. diversification models (Fitzjohn, 2010), so as to examine the role of N e in speciation and extinction patterns. Finally, the underlying codon model could be further elaborated (Rodrigue et al., 2010;De Maio et al., 2013), so as to achieve a more complete integration of polymorphism and divergence in model-based molecular evolutionary studies (Hernandez et al., 2011). Materials & MethodsCoding sequence data, phylogenetic tree and fossil calibration The coding sequences were taken from Perelman et al. (2011) and modified. It consists in a modified subset, codon compliant, based on 54 nuclear autosomal genes in 61 species of primates, and of a total length 15.9 kb. We used the tree topology published by Perelman et al. (itself based on a maximum likelihood analysis), as well as the eight fossil calibrations that were used in this previous study to estimate divergence times. These calibrations were encoded as hard constraints on the molecular dating analysis.

show abstract

“…A number of technical difficulties stand in the way of this comparison. Germline mutations are rare (on the order of 100 in a 6-Gb genome) [39]. Reliable estimates are therefore exquisitely sensitive to false negative and positive rates, which, in turn, depend on sequencing coverage, the reference genome quality, and the variant-calling pipeline.…”

Section: Plos Biologymentioning

confidence: 99%

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

et al. 2020

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Evolution of the mutation rate across primates

Cited by 46 publications

References 52 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

Reconstructing the history of variation in effective population size along phylogenies

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

Contact Info

Product

Resources

About