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Mutation rates and the evolution of germline structure.

Scally A - Philos. Trans. R. Soc. Lond., B, Biol. Sci. (2016)

Bottom Line: 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.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'.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK aos21@cam.ac.uk.

No MeSH data available.


Related in: MedlinePlus

Models of human mutation rate slowdown with changing life-history parameters. Dotted line: simple scaling of mutation rate with generation time; dashed line: including a paternal age effect but with fixed age of puberty; solid line: including a paternal age effect and with age of puberty scaling with generation time, assuming tpub = 14 yr when tgen = 30 yr. Overall rates per basepair are scaled to be 0.5×10–9 bp–1 yr–1 when tgen = 30 yr.
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RSTB20150137F1: Models of human mutation rate slowdown with changing life-history parameters. Dotted line: simple scaling of mutation rate with generation time; dashed line: including a paternal age effect but with fixed age of puberty; solid line: including a paternal age effect and with age of puberty scaling with generation time, assuming tpub = 14 yr when tgen = 30 yr. Overall rates per basepair are scaled to be 0.5×10–9 bp–1 yr–1 when tgen = 30 yr.

Mentions: One possible explanation for the discrepancy between mutation rate estimates is that rates themselves may have changed during hominoid evolution. Since they are observed to differ between species across large evolutionary distances, a slowdown on this scale is not implausible a priori [11,12]. Indeed, great apes have evolved in several ways over this time, notably increasing in body mass [13]. This itself leads to an explanation for the putative slowdown based on a change in generation time (defined as the average time from zygote to zygote along a genetic lineage), since life-history parameters such as generation time scale with body mass across a wide range of mammal species [14,15]. Consider a simplistic model where the per-generation mutation rate μgen is constant and the mutation rate per year μ scales inversely with generation time: μ = μgen/tgen. Then an increase in generation time by a factor of almost two could account for the necessary reduction in yearly rate from approximately 1 × 10–9 bp–1 yr–1 in the past to 0.5 × 10–9 bp–1 yr–1 today (figure 1).Figure 1.


Mutation rates and the evolution of germline structure.

Scally A - Philos. Trans. R. Soc. Lond., B, Biol. Sci. (2016)

Models of human mutation rate slowdown with changing life-history parameters. Dotted line: simple scaling of mutation rate with generation time; dashed line: including a paternal age effect but with fixed age of puberty; solid line: including a paternal age effect and with age of puberty scaling with generation time, assuming tpub = 14 yr when tgen = 30 yr. Overall rates per basepair are scaled to be 0.5×10–9 bp–1 yr–1 when tgen = 30 yr.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4920338&req=5

RSTB20150137F1: Models of human mutation rate slowdown with changing life-history parameters. Dotted line: simple scaling of mutation rate with generation time; dashed line: including a paternal age effect but with fixed age of puberty; solid line: including a paternal age effect and with age of puberty scaling with generation time, assuming tpub = 14 yr when tgen = 30 yr. Overall rates per basepair are scaled to be 0.5×10–9 bp–1 yr–1 when tgen = 30 yr.
Mentions: One possible explanation for the discrepancy between mutation rate estimates is that rates themselves may have changed during hominoid evolution. Since they are observed to differ between species across large evolutionary distances, a slowdown on this scale is not implausible a priori [11,12]. Indeed, great apes have evolved in several ways over this time, notably increasing in body mass [13]. This itself leads to an explanation for the putative slowdown based on a change in generation time (defined as the average time from zygote to zygote along a genetic lineage), since life-history parameters such as generation time scale with body mass across a wide range of mammal species [14,15]. Consider a simplistic model where the per-generation mutation rate μgen is constant and the mutation rate per year μ scales inversely with generation time: μ = μgen/tgen. Then an increase in generation time by a factor of almost two could account for the necessary reduction in yearly rate from approximately 1 × 10–9 bp–1 yr–1 in the past to 0.5 × 10–9 bp–1 yr–1 today (figure 1).Figure 1.

Bottom Line: 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.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'.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK aos21@cam.ac.uk.

No MeSH data available.


Related in: MedlinePlus