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Mol.Evol

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Mol.Evol
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 classification that maximizes the correlation between KA/KS and KR/KC. An analysis of
3,375 orthologous gene groups among 5 mammalian species shows that our classification gives a significantly higher correlation coefficient between the 2 ratios than those of existing classifications. However, there are many orthologous gene groups with a low KA/KS but a high KR/KC ratio. Examining the functions of these genes, we found an overrepresentation of functional categories related to development. To determine if the overrepresentation is stage specific, we examined the expression patterns of these genes at different developmental stages of the mouse.
Interestingly, these genes are highly expressed in the early middle stage of development (blastocyst to amnion). It is commonly thought that developmental genes tend to be conservative in evolution, but some molecular changes in developmental stages should have contributed to morphological divergence in adult mammals. Therefore, we propose that the relaxed pressures indicated by the KR/KC ratio but not by KA/KS in the early middle stage of development may be important for the morphological divergence of mammals at the adult stage, whereas purifying selection detected by
KA/KS occurs in the early middle developmental stage.



Cited: Gojobori J, Tang H, Akey JM, Wu CI. 2007. Adaptive evolution in humans revealed by the negative correlation between the Gojobori T. 1983. Codon substitution in evolution and the ‘‘saturation’’ of synonymous changes. Genetics. 105:1011–1027. Grantham R. 1974. Amino acid difference formula to help explain protein evolution Hanada K, Gojobori T, Li WH. 2006. Radical amino acid change versus positive selection in the evolution of viral envelope Hill DP, Blake JA, Richardson JE, Ringwald M. 2002. Extension and integration of the gene ontology (GO): combining GO Hughes AL, Nei M. 1988. Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection Hughes AL, Ota T, Nei M. 1990. Positive Darwinian selection promotes charge profile diversity in the antigen-binding cleft Li WH, Gojobori T. 1983. Rapid evolution of goat and sheep globin genes following gene duplication Miyata T, Miyazawa S, Yasunaga T. 1979. Two types of amino acid substitutions in protein evolution Richardson MK. 1999. Vertebrate evolution: the developmental origins of adult variation Saitou N, Nei M. 1987. The neighbor-joining method: a new method for reconstructing phylogenetic trees Slack JM, Holland PW, Graham CF. 1993. The zootype and the phylotypic stage Smith JM, Smith NH. 1996. Synonymous nucleotide divergence: what is ‘‘saturation’’? Genetics Smith NG. 2003. Are radical and conservative substitution rates useful statistics in molecular evolution? J Mol Evol. Tang H, Wyckoff GJ, Lu J, Wu CI. 2004. A universal evolutionary index for amino acid changes Thompson JD, Higgins DG, Gibson TJ. 1994. Clustal W: improving the sensitivity of progressive multiple sequence Yang Z, Kumar S, Nei M. 1995. A new method of inference of ancestral nucleotide and amino acid sequences Zhang J. 2000. Rates of conservative and radical nonsynonymous nucleotide substitutions in mammalian nuclear genes Zhang J, Rosenberg HF, Nei M. 1998. Positive Darwinian selection after gene duplication in primate ribonuclease genes. Takashi Gojobori, Associate Editor Accepted July 16, 2007

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