Low mutation rate but high male-bias in the germline of a short-lived opossum.

Age and sex have been found to be important determinants of the mutation rate per generation in mammals, but the mechanisms underlying these factors are still unclear. One approach to distinguishing between alternative mechanisms is to study species that reproduce at very young ages, as competing hypotheses make different predictions about patterns of mutation in these organisms. Here, we study the germline mutation rate in the gray short-tailed opossum, Monodelphis domestica, a laboratory model species that becomes reproductively mature at less than six months of age. Whole-genome sequencing of 22 trios reveals one of the lowest mutation rates per generation found in mammals thus far (0.252 × 10-8 per base pair per generation at an average parental age of 313 days), which is expected given their early reproduction. We also examine the mutation spectrum and find fewer mutations at CpG sites in opossums than in humans, consistent with the lower CpG content in the opossum genome. We observe that two-thirds of mutations are inherited from the male parent in opossums, slightly lower than the degree of male bias observed in organisms that reproduce at much older ages. Nevertheless, the very young age at reproduction in opossums suggests that ongoing spermatogonial divisions in males after puberty are not the primary driver of the observed male mutation bias. These findings contribute to a growing body of evidence that the differences between male and female germline mutation may arise from mechanisms other than cell division post-puberty.