Reduction of synonymous substitutions in the core protein gene of hepatitis C virus.
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 x 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 x 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.
Ina
Y
Y
DNA Research Center, National Institute of Genetics, Mishima, Japan.
Mizokami
M
M
Ohba
K
K
Gojobori
T
T
D005075:Biological Evolution; D014644:Genetic Variation; D016174:Hepacivirus / Q000145:classification / Q000235:genetics*; D008969:Molecular Sequence Data; D010802:Phylogeny; D014758:Viral Core Proteins / Q000235:genetics*
D014758:Viral Core Proteins