Differences in the rare variant spectrum among human populations
Differences in the rare variant spectrum among human populations
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DOI：
10.1371/journal.pgen.1006581
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发表时间：
2017-02-01
期刊：
影响因子：
4.5
通讯作者：
Reich, David
中科院分区：
文献类型：
--
作者：
Mathieson, Iain;Reich, David
在基因组和人群中，突变发生的频率非常不同，导致分离多态的谱系不同。在这里，我们调查了代表世界上所有主要人口的人类基因组样本中罕见变异谱的变异。我们发现了至少两个明显的变异特征。其一，与先前报道的特征一致，其特征是西亚和南亚人的TCC和GT；TTC突变率增加，可能与甲基化鸟嘌呤脱氨基造成的损害的发生率或修复效率的差异有关。我们描述了这个特征的地理范围，并表明它可以在古人类的基因组中检测到，但不是古人类。第二个签名是某些美洲原住民的私人签名，集中在CpG遗址。我们表明，这种特征不是由CpG突变率的差异驱动的，而是这样一个事实的结果，即高度可变的CpG位点在人类群体中更有可能经历多个独立的突变，并且这些突变的谱对最近的人口学高度敏感。这两种影响都极大地影响了人类种群中稀有变异的光谱，在使用突变时钟来推断人口统计学时，应该考虑到这两种影响。
Mutations occur at vastly different rates across the genome, and populations, leading to differences in the spectrum of segregating polymorphisms. Here, we investigate variation in the rare variant spectrum in a sample of human genomes representing all major world populations. We find at least two distinct signatures of variation. One, consistent with a previously reported signature is characterized by an increased rate of TCC>TTC mutations in people from Western Eurasia and South Asia, likely related to differences in the rate, or efficiency of repair, of damage due to deamination of methylated guanine. We describe the geographic extent of this signature and show that it is detectable in the genomes of ancient, but not archaic humans. The second signature is private to certain Native American populations, and is concentrated at CpG sites. We show that this signature is not driven by differences in the CpG mutation rate, but is a result of the fact that highly mutable CpG sites are more likely to undergo multiple independent mutations across human populations, and the spectrum of such mutations is highly sensitive to recent demography. Both of these effects dramatically affect the spectrum of rare variants across human populations, and should be taken into account when using mutational clocks to make inference about demography.