Hibernation shows no apparent effect on germline mutation rates in grizzly bears

Abstract

A male mutation bias is observed across vertebrates, and, where data are available, this bias is accompanied by increased per-generation mutation rates with parental age. While continuing mitotic cell division in the male germline post-puberty has been proposed as the major cellular mechanism underlying both patterns, little direct evidence for this role has been found. Understanding the evolution of the per-generation mutation rate among species requires that we identify the molecular mechanisms that change between species. Here, we study the per-generation mutation rate in an extended pedigree of the brown (grizzly) bear, Ursus arctos horribilis. Brown bears hibernate for one-third of the year, a period during which spermatogenesis slows or stops altogether. The cessation of spermatogenesis is predicted to lessen the male mutation bias and to lower the per-generation mutation rate in this species. However, using whole-genome sequencing, we find that both male bias and per-generation mutation rates are the same as expected for a non-hibernating species. We also carry out a phylogenetic comparison of substitution rates along the lineage leading to brown bear and panda (a non-hibernating species) and find no slowing of the substitution rate in the hibernator. Our results contribute to accumulating evidence that suggests that male germline cell division is not the major determinant of mutation rates and mutation biases. The results also provide a quantitative basis for improved estimates of the timing of carnivore evolution.

A paternal bias in germline mutation is widespread in amniotes and can arise independently of cell divisions

“…Second, despite highly variable rates of germ cell division over human ontogenesis, germline mutations accumulate with absolute time in both sexes, resulting in a ratio of paternal-to-maternal germline mutation, α, of around 3.5 at puberty and very little increase with parental ages [21]. Third, studies in a dozen other mammals suggest that α ranges from 2 to 4 whether the species reproduces months, years or decades after birth [22][23][24], when estimates of germ cell division numbers at time of reproduction would predict a much wider range in α [13,22,25,26].…”

A beary good genome: Haplotype-resolved, chromosome-level assembly of the brown bear (Ursus arctos)

“…Here, we predict a nearly doubled N e compared to previous results (Cahill et al 2013; Kumar et al 2017; Endo et al 2021; Zhu et al 2020; Liu et al 2014; Lan et al 2022), which is consistent with expectations for having a mutation rate that is approximately halved (Nadachowska-Brzyska et al 2016). This mutation rate is likely more accurate since it was calculated directly through trio sequencing (Wang et al 2022).…”

“…We next generated PSMC curves with 100 bootstraps using the suggested parameters linked above, with a mutation rate of 0.9225 × 10-9 per bp per year (Wang et al 2022) and a generation time of 10 years. Although there are a number of different generation times used for bears, we selected a generation time of 10 because we believe this to be a conservative estimate of generation time based on previous field studies ( McLellan et al 2017).…”

A Beary Good Genome: Haplotype-Resolved, Chromosome-Level Assembly of the Brown Bear (Ursus arctos)

“…We next generated PSMC curves with 100 bootstraps using the suggested parameters linked above, with a mutation rate of 0.9225 × 10-9 per bp per year (Wang et al 2022b ) and a generation time of 10 years. Although there are a number of different generation times used for bears, we selected a generation time of 10 because we believe this to be a conservative estimate of generation time based on previous field studies ( McLellan et al 2017 ).…”