Evaluation of the effect of CpG hypermutability on human codon substitution

Kazuharu Misawa, Reiko F. Kikuno

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Understanding the cause underlying the changes in amino acid composition of proteins is essential for understanding protein evolution and function. Accurate models of DNA and protein evolution are essential for studying molecular evolution. Although many models have been developed, most models assume that each site evolves independently and that substitutions are time reversible. In mammals and other organisms, CpG hypermutability is one of the major causes of nucleotide mutations because CpG dinucleotides are often methylated at C, and the methyl-C mutation spontaneously deaminates to yield T about 3 times more rapidly than other types of point mutations. In this study, we evaluate the effect of CpG hypermutability on codon substitution by comparing thousands of coding regions in the human and chimpanzee genomes and by inferring ancestral sequences by using mouse as the outgroup. We found that 14% of synonymous and nonsynonymous substitutions on human genes were caused by CpG hypermutability. Based on these results, we developed a model that incorporates CpG hypermutability as well as the transition/transversion ratio and changes in the chemical properties of amino acids.

Original languageEnglish
Pages (from-to)18-22
Number of pages5
JournalGene
Volume431
Issue number1-2
DOIs
Publication statusPublished - 2009 Feb 15

Keywords

  • Context-dependent mutation
  • CpG hypermutability
  • Gain and loss of amino acids
  • Rates of molecular evolution

ASJC Scopus subject areas

  • Genetics

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