Hanada Kousuke, Gojobori Takashi, Li Wen-Hsiung
Department of Ecology and Evolution, University of Chicago 1101 East 57th Street, Chicago, IL, 60637, USA.
Gene. 2006 Dec 30;385:83-8. doi: 10.1016/j.gene.2006.06.029. Epub 2006 Aug 24.
To detect positive selection in protein-coding sequence evolution, the ratio of the nonsynonymous to synonymous substitution rate (K(A)/K(S)) is commonly used. When this ratio is higher than 1, positive selection on nonsynonymous changes is considered to have occurred. However, the question of what kinds of amino acid change are likely to be involved in positive selection has not been well studied, though intuitively it seems that radical changes frequently occur in positively selected changes. To address this question, we examined chemically radical and conservative replacements in the evolution of hepatitis C virus (HCV) protein sequences. In the envelope region, 34 positively and 440 negatively selected sites were identified by the K(A)/K(S) ratio. Radical and conservative changes were compared between the two types of selected sites using two methods. First, the numbers of radical and conservative replacements were counted at the positively and negatively selected sites according to three kinds of chemical classifications. In all three classifications, the resulting ratios of the two numbers were not statistically different for the two types of selected sites (P>0.05). Second, the distribution of chemical changes was compared between the two types of selected sites using two kinds of chemical distances. The distributions of the two chemical distances were not statistically different for the two types of selected sites (P>0.05). These results indicate that the ratio of chemically radical and conservative changes is similar for positively and negatively selected sites in the envelope protein of HCV or, in other words, there is no correlation between radical change and positive selection in the evolution of this protein.
为了检测蛋白质编码序列进化中的正选择，通常使用非同义替换率与同义替换率的比值（K(A)/K(S)）。当这个比值高于1时，就认为发生了对非同义变化的正选择。然而，关于哪些类型的氨基酸变化可能参与正选择的问题尚未得到充分研究，尽管直观上似乎在正选择的变化中经常发生剧烈变化。为了解决这个问题，我们研究了丙型肝炎病毒（HCV）蛋白质序列进化中的化学上的剧烈和保守替换。在包膜区域，通过K(A)/K(S)比值鉴定出34个正选择位点和440个负选择位点。使用两种方法比较了两种类型选择位点之间的剧烈和保守变化。首先，根据三种化学分类，统计正选择和负选择位点上的剧烈和保守替换的数量。在所有三种分类中，两种类型选择位点的这两个数量的所得比值在统计学上没有差异（P>0.05）。其次，使用两种化学距离比较了两种类型选择位点之间的化学变化分布。两种类型选择位点的两种化学距离分布在统计学上没有差异（P>0.05）。这些结果表明，在HCV包膜蛋白中，正选择和负选择位点的化学上的剧烈和保守变化的比值相似，或者换句话说，在该蛋白质的进化中，剧烈变化与正选择之间没有相关性。
