Synonymous codon selection in the hepatitis B virus translation initiation region

Abstract Hepatitis B virus (HBV) infection is a major health problem worldwide. This virus and its hosts are often fated to continual co-evolutionary interactions. Codon usage analysis has significance for studies of co-evolution between viruses, their hosts, and mRNA translation. Adaptation of the overall codon usage pattern of HBV to that of humans is estimated using the synonymous codon usage value (RSCU), and the synonymous codon usage biases for the translation initiation region (TIR) of HBV are analyzed by calculation of the usage fluctuation of each synonymous codon along the TIR (the first 50 codon sites of the whole coding sequence of HBV). With respect to synonymous codon usage, our results demonstrated that HBV had no significant tendency to select over-represented codons, but had a significant tendency to select certain under-represented codons in the viral genome. Within the three common HBV hosts, 14 of 59 codons had a similar usage pattern, suggesting that mutation pressure from this DNA virus played an important role in the formation of virus synonymous codon usage. In addition, there was no obvious trend for the codons with relatively low energy to be highly selected in the TIR of HBV, suggesting that the synonymous codon usage patterns for the TIR might not be affected by the nucleotide sequence secondary structure; however, synonymous codon usage in the TIR of HBV was influenced by the overall codon usage patterns of the hosts to some degree. Our results suggest that mutation pressure from HBV plays an important role in the formation of synonymous codon usage of the viral genome, while translation selection from the hosts contributes to virus translational fine-tuning.