More single‐nucleotide mutations surround small insertions than small deletions in primates
More single‐nucleotide mutations surround small insertions than small deletions in primates
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DOI：
10.1002/humu.22085
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发表时间：
2012-07
期刊：
影响因子：
3.9
通讯作者：
Shengfeng Huang;Ting Yu;Zelin Chen;Shaochun Yuan;Shangwu Chen;A. Xu
中科院分区：
文献类型：
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作者：
Shengfeng Huang;Ting Yu;Zelin Chen;Shaochun Yuan;Shangwu Chen;A. Xu
早期的研究表明，单核苷酸突变率在接近插入和缺失时增加，但尚未完全理解自然选择如何塑造全基因组范围内的插入缺失模式及其附近的单核苷酸突变。在这项研究中，我们发现，在灵长类动物中，小插入周围的单核苷酸突变比小缺失更多。这种模式影响接近插入缺失的<150个碱基对（bp）序列，并且在不同的基因组特性下持续存在，例如外显子/内含子/基因间背景、重复/非重复序列、复制定时、重组率、插入缺失密度和鸟嘌呤-胞嘧啶（GC）含量。我们提出了两个不同的，但不是相互排斥的，假设的机制来解释的模式。一种机制是，偏好插入形成的序列环境也可能有利于核苷酸取代。另一种机制与indel杂合性倾向于增加附近核苷酸取代率的假设有关。这意味着如果插入在杂合子中花费更多时间，插入可能会积累更多周围的单核苷酸变化。总之，我们描述了一个特殊的全基因组的进化模式的indels和附近的单核苷酸变化。这种模式可能是由自然选择和偏见灵长类动物的基因组进化和表型变异。Mutat 33：1099 - 1106，2012.© 2012 Wiley Periodicals，Inc.
Early studies have shown that single‐nucleotide mutation rates increase close to insertions and deletions, but it is not fully understood how natural selection shapes genome‐wide patterns of indels and their nearby single‐nucleotide mutations. In this study, we find that, in primates, more single‐nucleotide mutations surround small insertions than small deletions. This pattern affects <150 base pair (bp) sequences close to indels and persists under different genomic properties, such as exon/intron/intergenic contexts, repeated/nonrepeated sequences, replication timing, recombination rates, indel density, and guanine–cytosine (GC) content. We propose two different, but not mutually exclusive, hypothetical mechanisms to explain the pattern. One mechanism is that the sequence context preferring insertion formation may also favor nucleotide substitutions. Another mechanism is related to a hypothesis in which indel heterozygosity tends to increase nearby nucleotide substitution rates. It means that if insertions spend more time in heterozygotes, insertions may accumulate more surrounding single‐nucleotide changes. In conclusion, we characterize a special genome‐wide evolutionary pattern for indels and nearby single‐nucleotide changes. This pattern may be driven by natural selection and bias primates' genome evolution and phenotypic variations. Hum Mutat 33:1099–1106, 2012. © 2012 Wiley Periodicals, Inc.