Synonymous and nonsynonymous rate variation in nuclear genes of mammals

Ziheng Yang*, Rasmus Nielsen

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

491 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalJournal of Molecular Evolution
Volume46
Issue number4
Pages (from-to)409-418
Number of pages10
ISSN0022-2844
DOIs
Publication statusPublished - 23 Apr 1998
Externally publishedYes

Keywords

  • Codon substitution
  • Likelihood
  • Mammalian genes
  • Neutral theory
  • Nonsynonymous rates
  • Synonymous rates
  • Transition/transversion rate bias

Cite this