Gu Xun
Department of Genetics, Development and Cell Biology Center for Bioinformatics and Biological Statistics, Iowa State University, 536 Science II Hall, Ames, IA 50011, USA.
Genetica. 2007 May;130(1):93-7. doi: 10.1007/s10709-006-0022-5. Epub 2006 Nov 1.
In this study, I take a new approach to modeling the evolutionary constraint of protein sequence, introducing the stabilizing selection of protein function into the nearly-neutral theory. In other words, protein function under stabilizing selection generates the evolutionary conservation at the sequence level. With the help of random mutational effects of nucleotides on protein function, I have derived the distribution of selection coefficient among sites, called the S-distribution whose parameters have clear biological interpretations. Moreover, I have studied the inverse relationship between the evolutionary rate and the effective population size, showing that the number of molecular phenotypes of protein function, i.e., independent components in the fitness of the organism, may play a key role for the molecular clock under the nearly-neutral theory. These results are helpful for having a better understanding of the underlying evolutionary mechanism of protein sequences, as well as human disease-related mutations.
在本研究中，我采用了一种新方法来对蛋白质序列的进化约束进行建模，即将蛋白质功能的稳定选择引入近中性理论。换句话说，稳定选择下的蛋白质功能在序列水平上产生了进化保守性。借助核苷酸对蛋白质功能的随机突变效应，我推导出了位点间选择系数的分布，称为S分布，其参数具有明确的生物学解释。此外，我研究了进化速率与有效种群大小之间的反比关系，表明蛋白质功能的分子表型数量，即生物体适应性中的独立成分，在近中性理论下可能对分子钟起着关键作用。这些结果有助于更好地理解蛋白质序列的潜在进化机制以及与人类疾病相关的突变。
