TY - JOUR

T1 - Synonymous and nonsynonymous rate variation in nuclear genes of mammals

AU - Yang, Ziheng

AU - Nielsen, Rasmus

PY - 1998/4/23

Y1 - 1998/4/23

N2 - A maximum likelihood approach was used to estimate the synonymous and nonsynonymous substitution rates in 48 nuclear genes from primates, artiodactyls, and rodents. A codon-substitution model was assumed, which accounts for the genetic code structure, transition/transversion bias, and base frequency biases at codon positions. Likelihood ratio tests were applied to test the constancy of nonsynonymous to synonymous rate ratios among branches (evolutionary lineages). It is found that at 22 of the 48 nuclear loci examined, the nonsynonymous/synonymous rate ratio varies significantly across branches of the tree. The result provides strong evidence against a strictly neutral model of molecular evolution. Our likelihood estimates of synonymous and nonsynonymous rates differ considerably from previous results obtained from approximate pairwise sequence comparisons. The differences between the methods are explored by detailed analyses of data from several genes. Transition/transversion rate bias and codon frequency biases are found to have significant effects on the estimation of synonymous and nonsynonymous rates, and approximate methods do not adequately account for those factors. The likelihood approach is preferable, even for pairwise sequence comparison, because more realistic models about the mutation and substitution processes can be incorporated in the analysis.

AB - A maximum likelihood approach was used to estimate the synonymous and nonsynonymous substitution rates in 48 nuclear genes from primates, artiodactyls, and rodents. A codon-substitution model was assumed, which accounts for the genetic code structure, transition/transversion bias, and base frequency biases at codon positions. Likelihood ratio tests were applied to test the constancy of nonsynonymous to synonymous rate ratios among branches (evolutionary lineages). It is found that at 22 of the 48 nuclear loci examined, the nonsynonymous/synonymous rate ratio varies significantly across branches of the tree. The result provides strong evidence against a strictly neutral model of molecular evolution. Our likelihood estimates of synonymous and nonsynonymous rates differ considerably from previous results obtained from approximate pairwise sequence comparisons. The differences between the methods are explored by detailed analyses of data from several genes. Transition/transversion rate bias and codon frequency biases are found to have significant effects on the estimation of synonymous and nonsynonymous rates, and approximate methods do not adequately account for those factors. The likelihood approach is preferable, even for pairwise sequence comparison, because more realistic models about the mutation and substitution processes can be incorporated in the analysis.

KW - Codon substitution

KW - Likelihood

KW - Mammalian genes

KW - Neutral theory

KW - Nonsynonymous rates

KW - Synonymous rates

KW - Transition/transversion rate bias

UR - http://www.scopus.com/inward/record.url?scp=0031960185&partnerID=8YFLogxK

U2 - 10.1007/PL00006320

DO - 10.1007/PL00006320

M3 - Journal article

C2 - 9541535

AN - SCOPUS:0031960185

VL - 46

SP - 409

EP - 418

JO - Journal of Molecular Evolution

JF - Journal of Molecular Evolution

SN - 0022-2844

IS - 4

ER -