The human genome contains over 100 million SNPs, most of which are C/T (G/A) variations. The type and sequence context of these SNPs are not random, suggesting that they are caused by distinct mutational processes. Deciphering the mutational signatures is a crucial step to discovering the molecular processes responsible for DNA variations across human populations, and potentially for causing genetic diseases. Our analyses of the 1000 Genomes Project SNPs and germline de novo mutations suggest that at least four mutational processes are responsible for human genetic variations. One process is European-specific and no longer active. The remaining three processes are currently active in all human populations. Two of the active processes co-occur and leave a single joint mutational signature in human nuclear DNA. The third active process is specific to mitochondrial DNA, and inflicts C-to-T mutations at mostly non-CG sites. We found neither evidence of APOBEC-induced cytosine deamination in the human germline, nor de novo mutation enrichment within certain regions of the human genome.

中文翻译：

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人类DNA进化中突变过程的特征

人类基因组包含超过1亿个SNP，其中大多数是C / T（G / A）变异。这些SNP的类型和序列背景不是随机的，表明它们是由独特的突变过程引起的。解密突变特征是发现导致人类群体DNA变异并可能导致遗传疾病的分子过程的关键步骤。我们对1000个基因组计划SNP和种系从头突变的分析表明，至少四个突变过程是人类遗传变异的原因。一种过程是欧洲特定的，不再有效。其余三个过程目前在所有人口中都活跃。两个活跃过程同时发生并在人类核DNA中留下单个联合突变特征。第三个活跃过程是针对线粒体DNA的，并在大多数非CG位点造成C-to-T突变。我们没有发现人类种系中APOBEC诱导的胞嘧啶脱氨的证据，也没有发现人类基因组某些区域的从头突变富集。