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-to-TTC mutation rate in Europeans, indicates a burst of mutations from about 15,000 to 2,000 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.
- Kelley Harris
- Jonathan K Pritchard
- Jonathan K Pritchard
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Gilean McVean, Oxford University, United Kingdom
© 2017, Harris & Pritchard
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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