Ratios of radical to conservative amino acid replacement are affected by mutational and compositional factors and may not be indicative of positive Darwinian selection
Ratios of radical to conservative amino acid replacement are affected by mutational and compositional factors and may not be indicative of positive Darwinian selection
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DOI：
10.1093/oxfordjournals.molbev.a004161
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发表时间：
2002-07-01
影响因子：
10.7
通讯作者：
Graur, D
中科院分区：
文献类型：
--
作者：
Dagan, T;Talmor, Y;Graur, D
自由基与保守氨基酸替换的比率经常被用来推断积极的达尔文选择。这种方法是基于一种假设，即自由基替代比保守替代更有可能改善蛋白质的功能。因此，正选择在蛋白质的进化中起着重要的作用。在中立的情况下，激进与保守的比率会超过预期。在这里，我们研究了与选择无关的因素，即过渡-翻转比、密码子使用、遗传密码和氨基酸组成，影响激进-保守替代比的可能性。所有被研究的因素都被发现影响激进-保守替代比率。特别是氨基酸组成和过渡-翻转比被证明具有最深远的影响。因为所研究的因素中没有一个与选择（积极的或消极的）有任何关系，而且因为所有这些因素（单独或组合）都影响了一个被认为是积极选择的指标，我们得出结论，基于激进-保守替代比率的选择推断应该被怀疑。
The ratio of radical to conservative amino acid replacements is frequently used to infer positive Darwinian selection. This method is based on the assumption that radical replacements are more likely than conservative replacements to improve the function of a protein. Therefore, if positive selection plays a major role in the evolution of a protein. one would expect the radical-conservative ratio to exceed the expectation under neutrality. Here, we investigate the possibility that factors unrelated to selection, i.e., transition-transversion ratio, codon usage, genetic code, and amino acid composition, influence the radical-conservative replacement ratio. All factors that have been studied were found to affect the radical-conservative replacement ratio. In particular, amino acid composition and transition-transversion ratio are shown to have the most profound effects. Because none of the Studied factors had anything to do with selection (positive or otherwise) and also because all of them (singly or in combination) affected a measure that was supposed to be indicative of positive selection, we conclude that selectional inferences based on radical-conservative replacement ratios should be treated with Suspicion.