Evolution of the germline mutation rate across vertebrates

Abstract

The germline mutation rate determines the pace of genome evolution and is an evolving parameter itself1. However, little is known about what determines its evolution, as most studies of mutation rates have focused on single species with different methodologies2. Here we quantify germline mutation rates across vertebrates by sequencing and comparing the high-coverage genomes of 151 parent–offspring trios from 68 species of mammals, fishes, birds and reptiles. We show that the per-generation mutation rate varies among species by a factor of 40, with mutation rates being higher for males than for females in mammals and birds, but not in reptiles and fishes. The generation time, age at maturity and species-level fecundity are the key life-history traits affecting this variation among species. Furthermore, species with higher long-term effective population sizes tend to have lower mutation rates per generation, providing support for the drift barrier hypothesis3. The exceptionally high yearly mutation rates of domesticated animals, which have been continually selected on fecundity traits including shorter generation times, further support the importance of generation time in the evolution of mutation rates. Overall, our comparative analysis of pedigree-based mutation rates provides ecological insights on the mutation rate evolution in vertebrates.

Variation in mutation, recombination, and transposition rates inDrosophila melanogasterandDrosophila simulans

“…It has been hypothesised that the germline mutation rate in multicellular eukaryotes may be explained by an equilibrium between natural selection to minimise it and the power of genetic drift to overcome the effect of selection (Lynch et al 2016). However, to date, there are relatively few estimates of germline mutation rate from multicellular eukaryotes, and those estimates that we do have are patchily distributed across the tree of life (reviewed by Yoder and Tiley 2021; but see Bergeron et al 2023;Wang and Obbard 2023). On the one hand, mutation rates appear to differ markedly between some distantly related species.…”

Extensive variation in germlinede novomutations inPoecilia reticulata

“…P. Martin & Palumbit, 1993). However, poikilothermy does not itself explain DNM rate variation across vertebrates (Bergeron et al, 2023), suggesting that the role of homeostasis in DNM rate is small. Our large pedigrees, each comprised of 10 offspring, make it possible to assess DNM sharing among siblings, and thus assess the degree of mosaicism in the germline genome (Goldmann et al, 2019).…”

“…Recent sequencing-based approaches to study germline mutation have used pedigrees to characterize germline DNM, and revealed the influence of many factors, including generation time (Bergeron et al, 2023;Carlson et al, 2018;Francioli et al, 2015;Kong et al, 2012;Wang et al, 2022), life history (Bergeron et al, 2023), and number of cell divisions (Ellegren, 2007).…”

No general effects of advancing male age on ejaculates: a meta-analysis across the animal kingdom

“…Second, sperm are potentially more affected by advancing organismal age than eggs (Bronikowski et al, 2022;Nussey et al, 2009). This pattern is due to sperm being more active and shorter lived than eggs, and male germlines having higher rates of cell divisions and mutations (Bergeron et al 2023;Crow, 2000;Fischer and Riddle, 2018;Monaghan and Metcalfe, 2019), but poorer DNA repair machinery, than female germ cells (Reinhardt and Turnell, 2019). Consequently, there may be greater transmission of accumulated mutations to offspring, via the paternal germline (Bergeron et al 2023;Campbell and Eichler, 2013;de Manuel et al, 2022;Sharma et al, 2015).…”

“…This pattern is due to sperm being more active and shorter lived than eggs, and male germlines having higher rates of cell divisions and mutations (Bergeron et al 2023;Crow, 2000;Fischer and Riddle, 2018;Monaghan and Metcalfe, 2019), but poorer DNA repair machinery, than female germ cells (Reinhardt and Turnell, 2019). Consequently, there may be greater transmission of accumulated mutations to offspring, via the paternal germline (Bergeron et al 2023;Campbell and Eichler, 2013;de Manuel et al, 2022;Sharma et al, 2015). Third, male reproductive senescence can affect male and female fitness due to declines in fertilisation ability of males (Johnson and Gemmell, 2012;Paul and Robaire, 2013), or due to declines in offspring quality via paternal age effects (Eisenberg and Kuzawa, 2018;Pizzari et al, 2008;Schroeder et al, 2015;Priest et al, 2002;Preston et al, 2015).…”