Mutation rates and the evolution of germline structure
Published 20 June 2016. DOI: 10.1098/rstb.2015.0137
Cellular genealogies in a two-offspring family. Solid black lines represent cellular lineages; germ cell populations are shaded green (in females) or blue (in males), somatic cells are shaded orange. Darker somatic populations represent the cellular ancestors of somatic cells sampled in a sequencing experiment. (a–d) Possible configurations of germ and sampled somatic cellular lineages at the early post-zygotic stage: (a) any cell ancestral to sampled somatic and germ cells is ancestral to all such cells; (b) cells may be ancestral to all germ cells but only some sampled somatic cells; (c) cells may be ancestral to all sampled somatic cells but only some germ cells; (d) cells may be ancestral to some germ cells and some sampled somatic cells (meaning that some germ cells may be more closely related to some somatic cells than to other germ cells, and vice versa).
Genome sequencing studies of de novo mutations in humans have revealed surprising incongruities in our understanding of human germline mutation. In particular, the mutation rate observed in modern humans is substantially lower than that estimated from calibration against the fossil record, and the paternal age effect in mutations transmitted to offspring is much weaker than expected from our long-standing model of spermatogenesis. I consider possible explanations for these discrepancies, including evolutionary changes in life-history parameters such as generation time and the age of puberty, a possible contribution from undetected post-zygotic mutations early in embryo development, and changes in cellular mutation processes at different stages of the germline. I suggest a revised model of stem-cell state transitions during spermatogenesis, in which ‘dark’ gonial stem cells play a more active role than hitherto envisaged, with a long cycle time undetected in experimental observations. More generally, I argue that the mutation rate and its evolution depend intimately on the structure of the germline in humans and other primates.
This article is part of the themed issue ‘Dating species divergences using rocks and clocks'.
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