The Nonsynonymous/Synonymous Substitution Rate Ratio versus the Radical/ Conservative Replacement Rate Ratio in the Evolution of Mammalian Genes
Kousuke Hanada,* Shin-Han Shiu, and Wen-Hsiung Li*
*Department of Ecology and Evolution, University of Chicago; and Department of Plant Biology, Michigan State University There are 2 ways to infer selection pressures in the evolution of protein-coding genes, the nonsynonymous and synonymous substitution rate ratio (KA/KS) and the radical and conservative amino acid replacement rate ratio (KR/KC). Because the KR/KC ratio depends on the deﬁnition of radical and conservative changes in the classiﬁcation of amino acids, we develop an amino acid ...view middle of the document...
Introduction Selection pressure on protein-coding sequences is commonly estimated by the ratio of the nonsynonymous substitution rate (KA) to the synonymous substitution rate (KS) (Li and Gojobori 1983; Hughes and Nei 1988). If the KA/KS ratio is higher than 1, positive selection is assumed to have occurred during the evolution of the sequence. The ratio of the radical replacement rate (KR) to the conservative replacement rate (KC) has also been used to detect positive selection (Hughes et al. 1990). The KR/KC ratio is useful for examining selection pressure in distantly related proteincoding sequences because the KA/KS ratio cannot be accurately estimated in this case due to saturation of KS (Gojobori 1983; Smith JM and Smith NH 1996). Because there are 2 ways of inferring selection pressure on a sequence, an open question is whether these 2 approaches give the same conclusion or not. Zhang (2000) and Smith (2003) found that KA/KS is correlated with KR/KC based on the amino acid classiﬁcation that considers polarity and volume using 47 mammalian and 25 Drosophila genes. However, there are several types of amino acid classiﬁcations, and it is not known which classiﬁcation gives a KR/KC measure that best correlates with the KA/KS ratio. Therefore, we do not know the degree of correlation between the 2 ratios in general. In the present study, we searched for an amino acid classiﬁcation that gives the best correlation between the 2 ratios. This amino acid classiﬁcation is useful because the KR/KC ratio based on this classiﬁcation can identify genes undergoing similar selection pressures inferred by the KA/KS ratio between distant protein-coding sequences. Another issue is that it is likely that the 2 ratios are not completely correlated even if the amino acid classiﬁcation
Key words: positive selection, radical substitution, conservative substitution, classiﬁcation of amino acids, development. E-mail: email@example.com.
Mol. Biol. Evol. 24(10):2235–2241. 2007 doi:10.1093/molbev/msm152 Advance Access publication July 25, 2007 Ó The Author 2007. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: firstname.lastname@example.org
that gives the maximum correlation between the 2 ratios is used. To address the differences between the selection pressures inferred by KA/KS and KR/KC in the evolution of mammalian genes, we examined functions of genes that showed different selection pressures inferred by the 2 ratios using Gene Ontology (GO) categories and expression data of a representative mammal, the mouse.
Materials and Methods Construction of Orthologous Groups cDNA data of 5 mammalian species were retrieved from the Ensembl database (http://www.ensembl.org): Homo sapiens (NCBI35.may), Pan troglodytes (CHIMP1. may), Mus musculus (NCBIM33.may), Rattus norvegicus (RGSC3.4.may), and Canis familiaris (BROADD1.may). Reciprocal best hits...