Gojobori Jun, Tang Hua, Akey Joshua M, Wu Chung-I
Department of Biological Sciences, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):3907-12. doi: 10.1073/pnas.0605565104. Epub 2007 Feb 26.
The selective forces acting on amino acid substitutions may be different in the two phases of molecular evolution: polymorphism and fixation. Negative selection and genetic drift may dominate the first phase, whereas positive selection may become much more significant in the second phase. However, the conventional dichotomy of synonymous vs. nonsynonymous changes does not offer the resolution needed to study the dynamics of these two phases. Following previously published methods, we separated amino acid changes into 75 elementary types (1-bp substitution between their respective codons). The likelihood of each type of amino acid change becoming polymorphic (PI, which stands for "polymorphic index"), relative to synonymous changes, can then be calculated. Similarly, the likelihood of fixation (FI, for "fixation index"), conditional on common polymorphisms, is also calculated. Using Perlegen and HapMap data on human polymorphisms and the chimpanzee sequences as the outgroup, we compared the evolutionary dynamics of the 75 elementary changes in the two phases. We found a strong "L-shaped" negative correlation (P < 0.001) between FI and PI. Only those changes with low PIs show FI > 1, which is often a signature of adaptive evolution. These patterns suggest that negative and positive selection operate more effectively on the same set of amino acid changes and that approximately 10-13% of amino acid substitutions between humans and chimpanzee may be adaptive.
在分子进化的两个阶段——多态性阶段和固定阶段，作用于氨基酸替换的选择力可能有所不同。负选择和遗传漂变可能在第一阶段占主导，而正选择在第二阶段可能变得更为显著。然而，传统的同义突变与非同义突变的二分法并不能提供研究这两个阶段动态所需的分辨率。按照先前发表的方法，我们将氨基酸变化分为75种基本类型（其各自密码子之间的单碱基替换）。然后可以计算相对于同义变化，每种类型的氨基酸变化成为多态性的可能性（PI，代表“多态性指数”）。类似地，在常见多态性条件下的固定可能性（FI，即“固定指数”）也会被计算出来。利用人类多态性的Perlegen和HapMap数据以及黑猩猩序列作为外类群，我们比较了这两个阶段中75种基本变化的进化动态。我们发现FI和PI之间存在强烈的“L形”负相关（P < 0.001）。只有那些低PI的变化显示FI > 1，这通常是适应性进化的标志。这些模式表明，负选择和正选择在同一组氨基酸变化上更有效地发挥作用，并且人类与黑猩猩之间大约10 - 13%的氨基酸替换可能是适应性的。
