Rapid evolution of the human mutation spectrum
Rapid evolution of the human mutation spectrum
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DOI：
10.7554/elife.24284
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发表时间：
2017-04-25
期刊：
影响因子：
7.7
通讯作者：
Pritchard, Jonathan K.
中科院分区：
文献类型：
--
作者：
Harris, Kelly;Pritchard, Jonathan K.
DNA 是一种非常精确的复制和存储生物信息的介质。这种高保真度是数百个参与复制、校对和损伤修复的基因作用的结果。进化理论表明，在这样的系统中，选择去除少量或在特定序列背景下改变突变率的遗传变异的能力有限。与此一致的是，使用 SNV 变异作为突变输入的代理，我们在此报告，物种、人类大陆群体甚至一些密切相关的种群之间的突变谱存在很大差异。仔细检查一个信号，即欧洲人 TCC -> TTC 突变率的增加，表明大约 15,000 至 2000 年前发生了突变的爆发，可能是由于突变率遗传修饰剂的出现、漂移和最终消除。我们的结果表明，突变率可以在较短的进化时间尺度内显着进化，并表明绘制突变修饰符的可能性。
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.