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2017 ; 6
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Rapid evolution of the human mutation spectrum
#MMPMID28440220
Harris K
; Pritchard JK
Elife
2017[Apr]; 6
(ä): ä PMID28440220
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DNA is a remarkably precise medium for copying and storing biological
information. This high fidelity results from the action of hundreds of genes
involved in replication, proofreading, and damage repair. Evolutionary theory
suggests that in such a system, selection has limited ability to remove genetic
variants that change mutation rates by small amounts or in specific sequence
contexts. Consistent with this, using SNV variation as a proxy for mutational
input, we report here that mutational spectra differ substantially among species,
human continental groups and even some closely related populations. Close
examination of one signal, an increased TCC?TTC mutation rate in Europeans,
indicates a burst of mutations from about 15,000 to 2000 years ago, perhaps due
to the appearance, drift, and ultimate elimination of a genetic modifier of
mutation rate. Our results suggest that mutation rates can evolve markedly over
short evolutionary timescales and suggest the possibility of mapping mutational
modifiers.