Evolutionary distance estimation under heterogeneous substitution pattern among lineages

Koichiro Tamura, Sudhir Kumar

Research output: Contribution to journalArticlepeer-review

228 Scopus citations


Most of the sophisticated methods to estimate evolutionary divergence between DNA sequences assume that the two sequences have evolved with the same pattern of nucleotide substitution after their divergence from their most recent common ancestor (homogeneity assumption). If this assumption is violated, the evolutionary distance estimated will be biased, which may result in biased estimates of divergence times and substitution rates, and may lead to erroneous branching patterns in the inferred phylogenies. Here we present a simple modification for existing distance estimation methods to relax the assumption of the substitution pattern homogeneity among lineages when analyzing DNA and protein sequences. Results from computer simulations and empirical data analyses for human and mouse genes are presented to demonstrate that the proposed modification reduces the estimation bias considerably and that the modified method performs much better than the LogDet methods, which do not require the homogeneity assumption in estimating the number of substitutions per site. We also discuss the relationship of the substitution and mutation rate estimates when the substitution pattern is not the same in the lineages leading to the two sequences compared.

Original languageEnglish (US)
Pages (from-to)1727-1736
Number of pages10
JournalMolecular biology and evolution
Issue number10
StatePublished - Oct 1 2002


  • Base composition
  • Computer simulation
  • LogDet
  • Mutation rate
  • Substitution rate

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics


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