Evidence for recent, population-specific evolution of the human mutation rate
Evidence for recent, population-specific evolution of the human mutation rate
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DOI：
10.1073/pnas.1418652112
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发表时间：
2015-03-17
影响因子：
11.1
通讯作者：
Harris, Kelley
中科院分区：
文献类型：
--
作者：
Harris, Kelley
随着人类离开非洲，他们适应了新的环境挑战，包括暴露在诱变的太阳辐射下的变化。温带地区的人类获得了对紫外线相对透明的浅色皮肤，一些证据表明，他们的DNA损伤反应途径也经历了局部适应。这就提出了一种可能性，即不同的种群经历了影响基因组完整性的不同选择压力。在这里，我提供的证据表明，在欧洲人群中，一种特定突变类型的发生率最近有所增加，自欧洲人开始与亚洲人分化以来，在4万至8万年间，频率上升了50%。对1000个基因组数据中非洲、亚洲和欧洲特有的snp的比较表明，欧洲特有的变异丰富于过渡5'- tcc -3' -> 5‘- ttc -3’。虽然尚不清楚紫外线是否在改变欧洲突变谱中发挥了因果作用，但已知5'- tcc -3' -> 5‘- ttc -3’是黑色素瘤皮肤癌中最常见的体细胞突变，也是体外紫外线最常诱导的突变。不管因果关系如何，这一变化表明，即使从现代人类起源以来，DNA复制的保真度也没有保持稳定，在我们最近的进化史上可能发生了多次变化。
As humans dispersed out of Africa they adapted to new environmental challenges, including changes in exposure to mutagenic solar radiation. Humans in temperate latitudes have acquired light skin that is relatively transparent to UV light, and some evidence suggests that their DNA damage response pathways have also experienced local adaptation. This raises the possibility that different populations have experienced different selective pressures affecting genome integrity. Here, I present evidence that the rate of a particular mutation type has recently increased in the European population, rising in frequency by 50% during the 40,000-80,000 y since Europeans began diverging from Asians. A comparison of SNPs private to Africa, Asia, and Europe in the 1000 Genomes data reveals that private European variation is enriched for the transition 5'-TCC-3' -> 5'-TTC-3'. Although it is not clear whether UV played a causal role in changing the European mutational spectrum, 5'-TCC-3' -> 5'-TTC-3' is known to be the most common somatic mutation present in melanoma skin cancers, as well as the mutation most frequently induced in vitro by UV. Regardless of its causality, this change indicates that DNA replication fidelity has not remained stable even since the origin of modern humans and might have changed numerous times during our recent evolutionary history.