Analysis of nucleotide sequence variations in herpes simplex virus types 1and 2, and varicella-zoster virus

To analyze the difference in the degree of divergence between genes from id entical herpesvirus species, we examined the nucleotide sequence of genes f rom the herpes simplex virus type I (HSV-1) strains VR-3 and 17 encoding th ymidine kinase (TK), deoxyribonuclease (DNase), protein kinase (PK; UL13) a nd virion-associated host shutoff(vhs) protein (UL41). The frequency of nuc leotide substitutions per 1 kb in TK gene was 2.5 to 4.3 times higher than those in the other three genes. To prove that the polymorphism of HSV-1 TK gene is common characteristic of herpesvirus TK genes, we compared the dive rsity of TK genes among eight HSV-1, six herpes simplex virus type 2 (HSV-2 ) and seven varicella-zoster virus (VZV) strains. The average frequency of nucleotide substitutions per 1 kb in the TK gene of HSV-1 strains was 4-fol d higher than that in the TK gene of HSV-1, strains. The VZV TK gene was hi ghly conserved and only two nucleotide changes were evident in VZV strains. However, the rate of nonsynonymous substitutions in total nucleotide subst itutions was similar among the TK genes of the three viruses. This result i ndicated that the mutational rates differed, but there were no significant differences in selective pressure. We conclude that HSV-1 TK gene is highly diverged and analysis of variations in the gene is a useful approach for u nderstanding the molecular evolution of HSV-1 in a short period.