Construction Of Hepatitis B Virus Phylogenetic Relationship And Divergence Of Base Substitution

Part1Resolving Ambiguity in the Phylogenetic Relationship of Genotypes A, B, and C of Hepatitis B VirusHepatitis B virus (HBV) is an important infectious agent that causes widespread concern because billions of people are infected by at least8different HBV genotypes worldwide. The phylogenetic relationship of the HBV genotypes supplies important clues to the evolution and historical prevalence of HBV. Reconstruction of the phylogenetic relationship between HBV genotypes, however, is difficult. Specifically, the phylogenetic relationships among genotypes A, B, and C are not clear from previous studies because of the confounding effects of genotype recombination. To reveal the phylogenetic relationships, a phylogenetic tree was constructed in this study to represent majority of evolutionary relationships of the HBV genotypes.In the present study, the phylogenetic relationship of the HBV genotypes was reconstructed using consensus phylogeny of phylogenetic trees of HBV genome segments when the confounding effect of recombination was eliminated. The reconstructed phylogenetic tree captured the major phylogenetic relationship of HBV genotypes with high confidence. The reconstructed phylogenetic relationship revealed that genotypes B and C had a closer phylogenetic relationship than genotypes A and B or A and C. The finding showed a correlation between the geographic prevalence and phylogenetic relationship of the HBV genotypes.HBV genotypes B and C carried by many Asians may have a historical European origin based on their geographic prevalence and phylogenetic relationship. The serial phylogenetic methods proposed in this study provide an effective approach for reconstructing reliable phylogenetic relationships for viruses with possible genetic recombination. Part2Identifying Divergence of Genetic Substitution among Hepatitis B Virus LineagesGenetic substitution is a fundamental force that drives the evolution of all kinds of organisms, including the hepatitis B virus (HBV). Accumulation of genetic substitutions over time increases genetic divergence among individual sequences and leads to new genetic lineages. Because genetic variants have an important impact on both the biologic features of HBV and the clinical outcomes of HBV infection, it is important to understand the biology of HBV by examining the genetic substitution patterns. Using3287full-length HBV sequences, the substitution patterns of HBV genetic sites were compared among different HBV lineages. Twenty genome sites were identified in which pattern of historical genetic substitutions was significantly different in different HBV lineages. The results suggest that the evolution of the identified sites was promoted by "driver" mutations at some specific sites that determined the lineages based on the nucleotide. The findings of the20sites indicated the potential existence of more evolution-divergent sites in the HBV genome because the number of HBV sequences was limited in the present study and the evolutionary driving force of the "driver" mutations was probably weak for most of the HBV genome sites. Genetic substitutions in critical genome regions frequently affect clinical outcomes of HBV infection, such as the development of antiviral drug resistance and the progression to hepatocellular carcinoma. Therefore, the findings of the present substitution study will benefit not only HBV evolution research, but also efforts to explore the relationships between clinical outcome and genetic differences in HBV.