The variability of the hepatitis B virus genome: statistical analysis and biological implications

A statistical analysis of the nucleotide sequence variability in 14published hepatitis B virus (HBV) genomes was carried out using parametricand nonparametric methods. A parametric statistical model revealed that thedifferent regions of the genome differed significantly in theirvariability. The conclusion was supported by a nonparametric kernel-densitymodel of the HBV genome. Genes S, C, and P, region X, the precore region,and the pre-S2/pre-S1 regions were ranked in order of increasingvariability. In many instances, conserved regions of the genome identifiedwith sequences of known function in HBV biology. However, othercharacterized regions (such as pre-S) showed much variability despite theinvolvement of their encoded peptides in specific functions. Pointmutations that may result in the formation of stop codons and amino acidchanges may affect the clinical picture of HBV infection and may bereflected in atypical serological patterns.