Evaluation of the effect of CpG hypermutability on human codon substitution
Evaluation of the effect of CpG hypermutability on human codon substitution
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DOI：
10.1016/j.gene.2008.11.006
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发表时间：
2009-02-15
期刊：
影响因子：
3.5
通讯作者：
Kikuno, Reiko F.
中科院分区：
文献类型：
--
作者：
Misawa, Kazuharu;Kikuno, Reiko F.
了解蛋白质氨基酸组成变化的原因对于理解蛋白质的进化和功能至关重要。精确的DNA和蛋白质进化模型对于研究分子进化至关重要。虽然已经开发了许多模型，但大多数模型都假设每个位点独立进化，并且替换是时间可逆的。在哺乳动物和其他生物中，CpG高易变性是核苷酸突变的主要原因之一，因为CpG二核苷酸通常在C位点甲基化，甲基C突变自发脱氨产生T的速度比其他类型的点突变快3倍。在这项研究中，我们通过比较人类和黑猩猩基因组中的数千个编码区，并以小鼠为外群推断祖先序列，来评估CpG超突变对密码子替换的影响。我们发现14%的人类基因的同义和非同义替换是由CpG超突变引起的。基于这些结果，我们开发了一个包含CpG超易变性、转换/翻转比和氨基酸化学性质变化的模型。(C) 2008 Elsevier B.V.版权所有
Understanding the cause underlying the changes in amino acid composition of proteins is essential for understanding protein evolution and function. Accurate models of DNA and protein evolution are essential for studying molecular evolution. Although many models have been developed, most models assume that each site evolves independently and that substitutions are time reversible. In mammals and other organisms, CpG hypermutability is one of the major causes of nucleotide mutations because CpG dinucleotides are often methylated at C, and the methyl-C mutation spontaneously deaminates to yield T about 3 times more rapidly than other types of point mutations. In this study, we evaluate the effect of CpG hypermutability on codon substitution by comparing thousands of coding regions in the human and chimpanzee genomes and by inferring ancestral sequences by using mouse as the outgroup. We found that 14% of synonymous and nonsynonymous substitutions on human genes were caused by CpG hypermutability. Based on these results, we developed a model that incorporates CpG hypermutability as well as the transition/transversion ratio and changes in the chemical properties of amino acids. (C) 2008 Elsevier B.V. All rights reserved.