Abstract
BackgroundHepatitis 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.ObjectiveThe 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.MethodsThe 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).ResultsThe 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.ConclusionsNucleotide 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.
Highlights
Hepatitis B virus (HBV) infection, the main causal factor for liver diseases such hepatitis, cirrhosis and liver cancer, is a significant global health concern worldwide (Benhenda et al 2013; Binh et al 2019; Bonvicino et al 2014; Kim et al 2007, 2017; Sarkar and Chakravarty 2015; Shih et al 2018)
Neighbor-Joining phylogenetic tree analysis showed that there were few substitutions in the sequences. They could be distinctly clustered to the reference sequences obtained from the National Center for Biotechnology Information (NCBI) database (Fig. 1)
There was a significant difference in HBV sequences from different genotypes despite their high identity (Fig. 1)
Summary
Hepatitis B virus (HBV) infection, the main causal factor for liver diseases such hepatitis, cirrhosis and liver cancer, is a significant global health concern worldwide (Benhenda et al 2013; Binh et al 2019; Bonvicino et al 2014; Kim et al 2007, 2017; Sarkar and Chakravarty 2015; Shih et al 2018). The HBV genome evolution depends on the complex interaction between viral and host factors, which determines the persistence and progression of HBV infection. Phylogenetic studies of HBV genome have revealed at least ten HBV genotypes, designated A–J (Tian and Jia 2016). 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. The ENC values indicated a weak codon usage bias (CUB) in 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
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