False-positive results obtained from the branch-site test of positive selection
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- Suzuki Yoshiyuki
- Institute of Molecular Evolutionary Genetics and Department of Biology, The Pennsylvania State University Center for Information Biology and DNA Data Bank of Japan, National Institute of Genetics
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Description
Natural selection operating at the amino acid sequence level can be detected by comparing the rates of synonymous (rS) and nonsynonymous (rN) nucleotide substitutions, where rN/rS (ω) > 1 and ω < 1 suggest positive and negative selection, respectively. The branch-site test has been developed for detecting positive selection operating at a group of amino acid sites for a pre-specified (foreground) branch of a phylogenetic tree by taking into account the heterogeneity of ω among sites and branches. Here the performance of the branch-site test was examined by computer simulation, with special reference to the false-positive rate when the divergence of the sequences analyzed was small. The false-positive rate was found to inflate when the assumptions made on the ω values for the foreground and other (background) branches in the branch-site test were violated. In addition, under a similar condition, false-positive results were often obtained even when Bonferroni correction was conducted and the false-discovery rate was controlled in a large-scale analysis. False-positive results were also obtained even when the number of nonsynonymous substitutions for the foreground branch was smaller than the minimum value required for detecting positive selection. The existence of a codon site with a possibility of occurrence of multiple nonsynonymous substitutions for the foreground branch often caused the branch-site test to falsely identify positive selection. In the re-analysis of orthologous trios of protein-coding genes from humans, chimpanzees, and macaques, most of the genes previously identified to be positively selected for the human or chimpanzee branch by the branch-site test contained such a codon site, suggesting a possibility that a significant fraction of these genes are false-positives.<br>
Journal
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- Genes & Genetic Systems
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Genes & Genetic Systems 83 (4), 331-338, 2008
The Genetics Society of Japan
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Details 詳細情報について
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- CRID
- 1390282680450360704
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- NII Article ID
- 10024396599
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- NII Book ID
- AA11077421
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- ISSN
- 18805779
- 13417568
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- NDL BIB ID
- 9663691
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- CiNii Articles
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- Abstract License Flag
- Disallowed