Reduction of synonymous substitutions in the core protein gene of hepatitis C virus

Yasuo Ina*, Masashi Mizokami, Kenichi Ohba, Takashi Gojobori

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

68 Scopus citations


Molecular evolutionary analyses were carried out to elucidate the phylogenetic relationships, the evolutionary rate, and the divergence times of hepatitis C viruses. Using the nucleotide sequences of the viruses isolated from various locations in the world, we constructed phylogenetic trees. The trees showed that strains isolated from a single location were not necessarily clustered as a group. This suggests that the viruses may be transferred with blood on a worldwide scale. We estimated the evolutionary rates at synonymous and nonsynonymous sites for all genes in the viral genome. We then found that the rate (1.35 × 10−3 per site per year) at synonymous sites for the C gene was much smaller than those for the other genes (e.g., 6.29 × 10−3 per site per year for the E gene). This indicates that a special type of functional constraint on synonymous substitutions may exist in the C gene. Because we found an open reading frame (ORF) with the C gene region, the possibility exists that synonymous substitutions for the C gene are constrained by the overlapping ORF whose reading frame is different from that of the C gene. Applying the evolutionary rates to the trees, we also suggest that major groups of hepatitis C viruses diverged from their common ancestor several hundred years ago.

Original languageEnglish (US)
Pages (from-to)50-56
Number of pages7
JournalJournal of Molecular Evolution
Issue number1
StatePublished - Jan 1994
Externally publishedYes


  • Evolutionary rate
  • Functional constraints
  • Hepatitis C virus
  • Reduction of nucleotide substitutions
  • Synonymous substitutions

ASJC Scopus subject areas

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


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