Intragenic variation of synonymous substitution rates is caused by nonrandom mutations at methylated CpG

Kazuhisa Tsunoyama, Matthew I. Bellgard, Takashi Gojobori*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

It has been observed that synonymous substitution rates vary among genes in various organisms, although the cause of the variation is unresolved. At the intragenic level, however, the variation of synonymous substitutions is somewhat controversial. By developing a rigorous statistical test and applying the test to 418 homologous gene pairs between mouse and rat, we found that more than 90% of gene pairs showed a statistical significance in intragenic variation of synonymous substitution rates. Moreover, by examining all conceivable possibilities for the cause of the variation, we successfully found that intragenic variation of synonymous substitutions in mammalian genes is caused mainly by a nonrandom mutation due to the methylation of CpG dinucleotides rather than by functional constraints.

Original languageEnglish (US)
Pages (from-to)456-464
Number of pages9
JournalJournal of Molecular Evolution
Volume53
Issue number4-5
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Intragenic variation
  • Methylation
  • Molecular evolution
  • Synonymous substitution rates

ASJC Scopus subject areas

  • Genetics
  • Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Genetics(clinical)
  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Agricultural and Biological Sciences(all)
  • Agricultural and Biological Sciences (miscellaneous)

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