COMPLETE NUCLEOTIDE-SEQUENCES OF 6 HEPATITIS-B VIRAL GENOMES ENCODINGTHE SURFACE-ANTIGEN SUBTYPES AYW4, ADW4Q(-), AND ADRQ(-) AND THEIR PHYLOGENETIC CLASSIFICATION

The complete nucleotide sequences of six hepatitis B viral (HBV) genom es were determined by dideoxy chain termination sequencing of ten over lapping nucleotide fragments obtained by the polymerase chain reaction . Four of the genomes belonged to the two genomic groups E and F of HB V which have been previously identified by us on the basis of sequence divergences within the S gene. Genomic group E encodes the HBsAg subt ype ayw4, group F adw4q(-). The other two genomes were of Pacific orig in within group C and encoded adrq(-). The relationship of these compl ete human HBV genomes to 21 that have been previously published, toget her with one chimpanzee virus and four rodent hepadnaviral genomes, wa s investigated by constructing a phylogenetic tree utilizing a combina tion of distance matrix and approximate parsimonious methods. Thereby, the previously demonstrated segregation of human HBV strains into six genomic groups was confirmed. Both of the representatives of the grou ps E and F were found to differ by 8.1-13.6% and by 12.8-15.5% from th e genomes of the other genomic groups and by 1.5 and 3.7% from each ot her. Since they differed by more than 8% from the genomes in the other groups, the limit originally used to define HBV genomic groups, their status as new genomic groups was confirmed. The two Pacific group C s trains were found to differ by 2.7% from each other and by 4.1 to 5.4% from other group C genomes, suggesting that they diverged early from the other group C genomes. According to both the overall similarity an d the phylogenetic dendrogram the F strains formed the most divergent cluster of HBV genomes favoring the concept that they represented the original HBV strains of the New World. The next split in the dendrogra m segregated the A, D, E and the chimpanzee strains from the Asian B a nd C strains. Information on the nucleotide sequences and their encode d products of HBV strains of different genomic groups will provide a b asis to understand biological variations of the HBV infection in diffe rent parts of the world.