We have proposed that hepatitis C virus should be classified into eleven genetic groups (types) which further divide into more than 80 genotypes (subtypes). However, only eight genetic groups (1-6, 10 and 11) have been defined on the basis of the full-length sequence. Hence, the entire nucleotide sequences of three HCV isolates in genetic groups 7-9 have now been determined. Phylogenetic analysis over the full-length sequences of these three isolates, along with 30 more in the other eight genetic groups, indicated that genetic groups 6-9 and 11 have bifurcated from a common branch and groups 3 and 10 from another. In the former branch groups 7 and 11, and groups 8 and 9, are closely related. Consequently, HCV can be classified into either eleven (1-11) or six groups (1; 2; 3 and 10; 4; 5; 6-9 and 11), allowing a clear separation of group and genotype similarity within the NS5b region or a subregion of 1093 nt. When pairwise comparison of 1093 nt in the NS5b sequence was performed on 106 HCV isolates of 36 genotypes in eleven genetic groups, they were classified into either eleven (1-11) or six (1; 2; 3 and 10; 4; 5; 6-9 and 11) genetic groups. However, group and genotype similarities were not clearly separable in either classification. The overlapping range was smaller using the classification into eleven genetic groups as compared to six genetic groups (2.7 vs 4-7%). These results indicate that HCV might not have evolved in the two-tiered fashion, at least in a strict sense.


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