A space-time process model for the evolution of DNA sequences

Genetics. 1995 Feb;139(2):993-1005. doi: 10.1093/genetics/139.2.993.


We describe a model for the evolution of DNA sequences by nucleotide substitution, whereby nucleotide sites in the sequence evolve over time, whereas the rates of substitution are variable and correlated over sites. The temporal process used to describe substitutions between nucleotides is a continuous-time Markov process, with the four nucleotides as the states. The spatial process used to describe variation and dependence of substitution rates over sites is based on a serially correlated gamma distribution, i.e., an auto-gamma model assuming Markov-dependence of rates at adjacent sites. To achieve computational efficiency, we use several equal-probability categories to approximate the gamma distribution, and the result is an auto-discrete-gamma model for rates over sites. Correlation of rates at sites then is modeled by the Markov chain transition of rates at adjacent sites from one rate category to another, the states of the chain being the rate categories. Two versions of nonparametric models, which place no restrictions on the distributional forms of rates for sites, also are considered, assuming either independence or Markov dependence. The models are applied to data of a segment of mitochondrial genome from nine primate species. Model parameters are estimated by the maximum likelihood method, and models are compared by the likelihood ratio test. Tremendous variation of rates among sites in the sequence is revealed by the analyses, and when rate differences for different codon positions are appropriately accounted for in the models, substitution rates at adjacent sites are found to be strongly (positively) correlated. Robustness of the results to uncertainty of the phylogenetic tree linking the species is examined.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Evolution*
  • Codon / genetics
  • DNA, Mitochondrial / genetics*
  • Genetic Variation / physiology*
  • Likelihood Functions
  • Markov Chains
  • Models, Genetic*
  • Primates / genetics


  • Codon
  • DNA, Mitochondrial