Estimation of DNA sequence context-dependent mutation rates using primate genomic sequences

Wei Zhang, Gerard G. Bouffard, Susan S. Wallace, Jeffrey P. Bond*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

It is understood that DNA and amino acid substitution rates are highly sequence context-dependent, e.g., C→T substitutions in vertebrates may occur much more frequently at CpG sites and that cysteine substitution rates may depend on support of the context for participation in a disulfide bond. Furthermore, many applications rely on quantitative models of nucleotide or amino acid substitution, including phylogenetic inference and identification of amino acid sequence positions involved in functional specificity. We describe quantification of the context dependence of nucleotide substitution rates using baboon, chimpanzee, and human genomic sequence data generated by the NISC Comparative Sequencing Program. Relative mutation rates are reported for the 96 classes of mutations of the form 5′αβγ3′ → 5′αδγ3′, where α, β, γ, and δ are nucleotides and β ≠ δ, based on maximum likelihood calculations. Our results confirm that C→T substitutions are enhanced at CpG sites compared with other transitions, relatively independent of the identity of the preceding nucleotide. While, as expected, transitions generally occur more frequently than transversions, we find that the most frequent transversions involve the C at CpG sites (CpG transversions) and that their rate is comparable to the rate of transitions at non-CpG sites. A four-class model of the rates of context-dependent evolution of primate DNA sequences, CpG transitions > non-CpG transitions ≈ CpG transversions > non-CpG transversions, captures qualitative features of the mutation spectrum. We find that despite qualitative similarity of mutation rates among different genomic regions, there are statistically significant differences.

Original languageEnglish (US)
Pages (from-to)207-214
Number of pages8
JournalJournal of Molecular Evolution
Volume65
Issue number3
DOIs
StatePublished - Oct 1 2007

Keywords

  • CpG dinucleotide
  • Genomics
  • Maximum likelihood
  • Molecular evolution
  • Mutation
  • Substitution
  • Transition mutation
  • Transversion mutation

ASJC Scopus subject areas

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

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