A codon-based model of nucleotide substitution for protein-coding DNA sequences

Mol Biol Evol. 1994 Sep;11(5):725-36. doi: 10.1093/oxfordjournals.molbev.a040153.


A codon-based model for the evolution of protein-coding DNA sequences is presented for use in phylogenetic estimation. A Markov process is used to describe substitutions between codons. Transition/transversion rate bias and codon usage bias are allowed in the model, and selective restraints at the protein level are accommodated using physicochemical distances between the amino acids coded for by the codons. Analyses of two data sets suggest that the new codon-based model can provide a better fit to data than can nucleotide-based models and can produce more reliable estimates of certain biologically important measures such as the transition/transversion rate ratio and the synonymous/nonsynonymous substitution rate ratio.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemical Phenomena
  • Chemistry, Physical
  • Codon / genetics*
  • DNA / genetics*
  • Genes*
  • Globins / genetics
  • Glucose-1-Phosphate Adenylyltransferase
  • Likelihood Functions
  • Mammals / classification
  • Mammals / genetics
  • Markov Chains
  • Models, Genetic*
  • Nucleotidyltransferases / genetics
  • Phylogeny*
  • Point Mutation*
  • Proteins / genetics*


  • Codon
  • Proteins
  • Globins
  • DNA
  • Nucleotidyltransferases
  • Glucose-1-Phosphate Adenylyltransferase