Molecular evolution of the hepatitis B virus genome

Abstract

The hepatitis B virus (HBV) has a circular DNA genome of about 3,200 base pairs. Economical use of the genome with overlapping reading frames may have led to severe constraints on nucleotide substitutions along the genome and to highly variable rates of substitution among nucleotide sites. Nucleotide sequences from 13 complete HBV genomes were compared to examine such variability of substitution rates among sites and to examine the phylogenetic relationships among the HBV variants. The maximum likelihood method was employed to fit models of DNA sequence evolution that can account for the complexity of the pattern of nucleotide substitution. Comparison of the models suggests that the rates of substitution are different in different genes and codon positions; for example, the third codon position changes at a rate over ten times higher than the second position. Furthermore, substantial variation of substitution rates was detected even after the effects of genes and codon positions were corrected; that is, rates are different at different sites of the same gene or at the same codon position. Such rates after the correction were also found to be positively correlated at adjacent sites, which indicated the existence of conserved and variable domains in the proteins encoded by the viral genome. A multiparameter model validates the earlier finding that the variation in nucleotide conservation is not random around the HBV genome. The test for the existence of a molecular clock suggests that substitution rates are more or less constant among lineages. The phylogenetic relationships among the viral variants were examined. Although the data do not seem to contain sufficient information to resolve the details of the phylogeny, it appears quite certain that the serotypes of the viral variants do not reflect their genetic relatedness.

Best‐fit Maximum‐likelihood Models for Phylogenetic Inference: Empirical Tests With Known Phylogenies

“…This result is not surprising, because our bacteriophage lineages are known to contain a large number of invariable sites due to a pronounced mutagen bias (Cunningham et al 1997), and is consistent with empirical studies that have found significant rate heterogeneity in most DNA sequences surveyed, ranging from viruses to mammals (Sullivan et al 1995;Yang et al 1995;Huelsenbeck 1997).…”

Phylogenetic Relationships Among the Phrynosomatid Sand Lizards Inferred from Mitochondrial DNA Sequences Generated by Heterogeneous Evolutionary Processes

“…The test statistic is assumed to be ;);: ^ distributed, with the degrees of freedom equal to the difference in the number of parameters between the two models. Theoretically, the use of the i'^ distribution is valid only when the likelihoods of the nested models are computed on the true topology (Yang et al, 1995a); however, Yang et al (1995b) have suggested that uncertainty about phylogeny is not a practical problem because differences between substitution models are most often greater than differences between topologies. Because it was impossible for us to know whether we were assessing the true topology, we compared the 16 nested models using several alternative topologies representing rival phylogenetic hypotheses (Fig.…”

A unique segment of the hepatitis B virus group A genotype identified in isolates from South Africa.

“…when isolates of known serotype are sequenced, no genetic relatedness is evident (Yang et al, 1995). Alignment, comparison and phylogenetic analysis of sequence data from various parts of the world show that HBV clusters into six genotypic groups, A to F (Norder et al, 1993).…”