Reliabilities of identifying positive selection by the branch-site and the site-prediction methods Export

@article{citeulike:4269813, abstract = {10.1073/pnas.0901855106 Natural selection operating in protein-coding genes is often studied by examining the ratio (\"{I}‰) 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 \^{a}‰ˆ80 or smaller. Because the \"{I}‰ 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 \"{I}‰ values, which may not have anything to do with functional changes. The codon sites showing functional changes generally do not show a high \"{I}‰ value. To understand adaptive evolution, some form of experimental confirmation is necessary.}, author = {Nozawa, Masafumi and Suzuki, Yoshiyuki and Nei, Masatoshi}, citeulike-article-id = {4269813}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0901855106}, citeulike-linkout-1 = {http://www.pnas.org/content/0901855106v1//.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/0901855106v1//.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/19339501}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=19339501}, day = {21}, doi = {10.1073/pnas.0901855106}, journal = {Proceedings of the National Academy of Sciences}, keywords = {adaptation, amino-acid, likelihood, methods, protein, selection, substitution-models, vertebrates}, month = {April}, number = {16}, pages = {6700--6705}, posted-at = {2009-04-24 09:15:52}, priority = {2}, title = {Reliabilities of identifying positive selection by the branch-site and the site-prediction methods}, url = {http://dx.doi.org/10.1073/pnas.0901855106}, volume = {106}, year = {2009} }

TY - JOUR ID - citeulike:4269813 L3 - citeulike-article-id:4269813 N2 - 10.1073/pnas.0901855106 Natural selection operating in protein-coding genes is often studied by examining the ratio (ω) 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 ≈80 or smaller. Because the ω 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 ω values, which may not have anything to do with functional changes. The codon sites showing functional changes generally do not show a high ω value. To understand adaptive evolution, some form of experimental confirmation is necessary. IS - 16 JF - Proceedings of the National Academy of Sciences EP - 6705 TI - Reliabilities of identifying positive selection by the branch-site and the site-prediction methods VL - 106 SP - 6700 KW - adaptation KW - amino-acid KW - likelihood KW - methods KW - protein KW - selection KW - substitution-models KW - vertebrates AU - Nozawa, Masafumi AU - Suzuki, Yoshiyuki AU - Nei, Masatoshi PY - 2009/04/21/ UR - http://dx.doi.org/10.1073/pnas.0901855106 ER -