期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：16
页码：6700-6705
DOI：10.1073/pnas.0901855106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Natural selection operating in protein-coding genes is often studied by examining the ratio ({omega}) of the rates of nonsynonymous to synonymous nucleotide substitution. The branch-site method (BSM) based on a likelihood ratio test is one of such tests to detect positive selection for a predetermined branch of a phylogenetic tree. However, because the number of nucleotide substitutions involved is often very small, we conducted a computer simulation to examine the reliability of BSM in comparison with the small-sample method (SSM) based on Fisher's exact test. The results indicate that BSM often generates false positives compared with SSM when the number of nucleotide substitutions is {approx}80 or smaller. Because the {omega} value is also used for predicting positively selected sites, we examined the reliabilities of the site-prediction methods, using nucleotide sequence data for the dim-light and color vision genes in vertebrates. The results showed that the site-prediction methods have a low probability of identifying functional changes of amino acids experimentally determined and often falsely identify other sites where amino acid substitutions are unlikely to be important. This low rate of predictability occurs because most of the current statistical methods are designed to identify codon sites with high {omega} values, which may not have anything to do with functional changes. The codon sites showing functional changes generally do not show a high {omega} value. To understand adaptive evolution, some form of experimental confirmation is necessary.
