Revising the human mutation rate: implications for understanding human evolution

@article{Scally2012RevisingTH,
  title={Revising the human mutation rate: implications for understanding human evolution},
  author={Aylwyn Scally and Richard Durbin},
  journal={Nature Reviews Genetics},
  year={2012},
  volume={13},
  pages={745-753}
}
It is now possible to make direct measurements of the mutation rate in modern humans using next-generation sequencing. These measurements reveal a value that is approximately half of that previously derived from fossil calibration, and this has implications for our understanding of demographic events in human evolution and other aspects of population genetics. Here, we discuss the implications of a lower-than-expected mutation rate in relation to the timescale of human evolution. 
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TLDR
It is proposed that the generation-time effect as it is usually understood cannot explain the observed rate variation, but instead that selection for decreased somatic mutation rates can be explained.
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TLDR
A revised model of stem cell state transitions during spermatogenesis is suggested, in which ‘dark’ gonial stem cells play a more active role than hitherto envisaged, with a long cycle time undetected in experimental observations, arguing that the mutation rate and its evolution depend intimately on the structure of the germline in humans and other primates.
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  • A. Scally
  • Biology, Medicine
    Philosophical Transactions of the Royal Society B: Biological Sciences
  • 2016
TLDR
A revised model of stem-cell state transitions during spermatogenesis is suggested, in which ‘dark’ gonial stem cells play a more active role than hitherto envisaged, with a long cycle time undetected in experimental observations, arguing that the mutation rate and its evolution depend intimately on the structure of the germline in humans and other primates.
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TLDR
Current debates that have been influenced by improvements in the ability to sequence DNA are reviewed and some of the analytical challenges that need to be overcome in order to fully exploit the rich historical information that is contained in the entirety of the human genome are discussed.
Determinants of mutation rate variation in the human germline.
TLDR
It is now feasible to count de novo mutations in transmissions from parents to offspring, and this direct approach yields a mutation rate that is twofold lower than previous estimates, calling into question the authors' understanding of the chronology of human evolution and raising the possibility that mutation rates have evolved relatively rapidly.
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