Created on 31st October 2016
DNA is a remarkably precise medium for copying and storing biological information, with a mutation rate in humans of about 1e-8 per base pair per generation. This extraordinary fidelity results from the combined action of hundreds of genes involved in DNA replication and proofreading, and repair of spontaneous damage. Recent studies of cancer have shown that mutation of specific genes often leads to characteristic mutational "signatures"--i.e., increased mutation rates within particular sequence contexts. We therefore hypothesized that more subtle variation in replication or repair genes within natural populations might also lead to differences in mutational signatures. As a proxy for mutational input, we examined SNV variation across human and other great ape populations. Remarkably we found that mutational spectra differ substantially among species, human continental groups and even, in some cases, between closely-related populations. Closer examination of one such signal, an increased rate of TCC->TTC mutations reported previously 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.Show more
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