Pervasive multinucleotide mutational events in eukaryotes.
Pervasive multinucleotide mutational events in eukaryotes.
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DOI：
10.1016/j.cub.2011.05.013
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发表时间：
2011-06-21
期刊：
影响因子：
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通讯作者：
Hahn MW
中科院分区：
文献类型：
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作者：
Schrider DR;Hourmozdi JN;Hahn MW
突变过程的许多方面都是非随机的，从转换相对于颠换的优势到CpG二核苷酸的较高突变率。然而，人们仍然经常假设单核苷酸突变是相互独立的，每一个都是由单独的突变事件引起的。发生多个，紧密间隔的替代似乎违反了独立的假设，往往被解释为适应性自然选择，平衡选择，或补偿进化的行动的证据。在这里，我们提供的证据表明，一个频繁的，广泛的多核苷酸突变过程中活跃在整个真核生物。来自突变累积实验、亲子三人组和人类多态性的基因组数据都表明，在DNA的短片段内同时发生核苷酸替换。无论物种如何，这种多核苷酸突变（MNM）始终占核苷酸取代总数的约3%。这些结果意味着，以前的适应性解释的多个，紧密间隔的取代可能是不必要的，MNM解释序列数据时必须考虑。
Many aspects of mutational processes are nonrandom, from the preponderance of transitions relative to transversions to the higher rate of mutation at CpG dinucleotides. However, it is still often assumed that single-nucleotide mutations are independent of one another, each being caused by separate mutational events. The occurrence of multiple, closely spaced substitutions appears to violate assumptions of independence and is often interpreted as evidence for the action of adaptive natural selection, balancing selection, or compensatory evolution. Here we provide evidence of a frequent, widespread multinucleotide mutational process active throughout eukaryotes. Genomic data from mutation-accumulation experiments, parent-offspring trios, and human polymorphisms all show that simultaneous nucleotide substitutions occur within short stretches of DNA. Regardless of species, such multinucleotide mutations (MNMs) consistently comprise ~3% of the total number of nucleotide substitutions. These results imply that previous adaptive interpretations of multiple, closely spaced substitutions may have been unwarranted and that MNMs must be considered when interpreting sequence data.