Relationships within and between genotypes of hepatitis B virus at points across the genome: footprints of recombination in certain isolates

Hepatitis B virus (HBV) was partitioned into type, subtype and isolate cate gories and the average evolutionary distances within and between categories was plotted at each of 54 points along the genome. The graphs showed alter nating variable and conserved domains within and between HBV subtypes and r evealed that some specimens assigned to different groups are more similar a cross several contiguous intervals than specimens belonging to the same gro up. Isolates were screened individually to determine their conformation to type and mosaic structure was identified in 14/65 specimens. Two entire cla des (six specimens) of genotype B had a B/C sequence switch in the core gen e region, whereas six genotype D specimens showed D/A switching in one or m ore regions of the genome. Genotype E was not separate from genotype D in t he X and C subgenomic regions. The nature and distribution of polymorphic s ites in mosaic regions was mapped at both the nucleotide and protein levels and the position of the variant fragments was related to mutational hot sp ots and linear epitopes of HBV. Mosaic structure was demonstrated statistic ally in 11 isolates using bootstrap resampling and recombination, rather th an random change, appeared to be the mechanism responsible. The sequence be tween and including the two DR regions was represented in all putative reco mbinants. The distribution of genetic distances over subgenomic regions sho wed that substitution rates are not constant among the lineages of HBV in t he preS regions. Genotype F is the most diverse group. Only genotypes A, C and F partition consistently into subtypes.