The characteristic of the synonymous codon usage and phylogenetic analysis of hepatitis B virus

Genes Genomics. 2020 Jul;42(7):805-815. doi: 10.1007/s13258-020-00932-w. Epub 2020 May 27.


Background: Hepatitis B virus (HBV) infection is a crucial medical issue worldwide. The dependence of HBV replication on host cell machineries and their co-evolutionary interactions prompt the codon usage pattern of viral genes to translation selection and mutation pressure.

Objective: The evolutionary characteristics of HBV and the natural selection effects of the human genome on the codon usage characteristics were analyzed to provide a basis for medication development for HBV infection.

Methods: The codon usage pattern of sequences from different HBV genotypes of our isolates and reference HBV genome sequences downloaded from the National Center for Biotechnology Information (NCBI) database were analyzed by computing the relative synonymous codon usage (RSCU), nucleotide content, codon adaptation index (CAI) and the effective number of codons (ENC).

Results: The highest ENC values were observed in the C genotypes, followed by the B genotypes. The ENC values indicated a weak codon usage bias (CUB) in HBV genome. The number of codons differentially used between the three genotypes was markedly higher than that of similarly used codons. High CAI values indicated a good adaptability of HBV to its host. The ENC plot indicated the occurrence of mutational pressure in the three genotypes. The mean Ka/Ks ratios in the three genotypes were lower than 1, which indicated a negative selection pressure. The CAI and GC3% plot indicated the existence of CUB in the HBV genome.

Conclusions: Nucleotide composition, mutation bias, negative selection and mutational pressure are key factors influencing the CUB and phylogenetic diversity in HBV genotypes. The data provided here could be useful for developing drugs for HBV infection.

Keywords: Codon usage pattern; Hepatitis B virus; Mutation pressure; Phylogenetic evolution; Translation selection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Codon Usage*
  • Evolution, Molecular
  • Female
  • Genes, Viral
  • Hepatitis B / genetics*
  • Hepatitis B virus / genetics*
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Phylogeny*
  • Sequence Analysis, DNA
  • Young Adult