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

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Abstract

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.

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Authors and Affiliations

  1. DNA Research Center, National Institute of Genetics, 411, Mishima, Japan

    Yasuo Ina & Takashi Gojobori

  2. Second Department of Internal Medicine, Nagoya City University Medical School, 467, Nagoya, Japan

    Masashi Mizokami & Kenichi Ohba

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  1. Yasuo Ina
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  2. Masashi Mizokami
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  3. Kenichi Ohba
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  4. Takashi Gojobori
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Correspondence to: T. Gojobori

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Ina, Y., Mizokami, M., Ohba, K. et al. Reduction of synonymous substitutions in the core protein gene of hepatitis C virus. J Mol Evol 38, 50–56 (1994). https://doi.org/10.1007/BF00175495

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  • DOI: https://doi.org/10.1007/BF00175495

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