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False-positive results obtained from the branch-site test of positive selection.
- Source :
- Genes & Genetic Systems; 2008, Vol. 83 Issue 4, p331-338, 8p
- Publication Year :
- 2008
-
Abstract
- Natural selection operating at the amino acid sequence level can be detected by comparing the rates of synonymous (r<subscript>s</subscript>) and nonsynonymous (r<subscript>N</subscript>) nucleotide substitutions, where r<subscript>N</subscript>/r<subscript>s</subscript> (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 co 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 co 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 13417568
- Volume :
- 83
- Issue :
- 4
- Database :
- Supplemental Index
- Journal :
- Genes & Genetic Systems
- Publication Type :
- Academic Journal
- Accession number :
- 35172812
- Full Text :
- https://doi.org/10.1266/ggs.83.331