The Codon Usage Bias and Mutational Landscape of Polymerase Overlapping Pre-Surface and Surface Genes of HBV

The Hepatitis B Virus (HBV) is a major health concern worldwide. Its genotypes show geographic distribution. Owing to its unique genomic organisation and nature of its replication cycle, this virus acquired the ability to persist inside the host for a long period of time, evolving under several selection pressures within a limited space of relaxed sites. This study explores the differences in codon usage, positional variability and the differential analysis of mutational landscape, of the pre-surface (PS) and surface (S) genes that overlap polymerase gene of HBV. It also explores the differences in variability of B/T cell epitope coding and non-coding regions in PS and S regions. Samples were collected from chronically infected patients in Saudi Arabia, who had not received anti-viral treatment. The DNA molecules of the HBV extracted from serum samples were amplified and then sequenced for PS and S region. The sequences were genotyped, and the variant frequency of synonymous and non-synonymous mutations in PS and S genes and their overlapping P gene regions were determined. The positional Shannon entropy were determined and compared within and between PS and S regions of HBV. The findings reveal higher variability in the PS region compared to that of the S region. Most of the synonymous mutations in the PS and S gene occur at position S3P1 causing a non-synonymous mutation in the overlapping Pol gene. The non-synonymous mutations in the S region are comparatively well tolerated by the P gene compared to the non-synonymous mutations occurring in the PS gene. A higher transversion was observed at the S1p2 codon site of both PS and S genes. The mutations in the PS and S genes and their overlapping Pol gene show positional and compositional pattern of distribution. There was a codon usage-bias observed between the PS and S regions. In the PS region codons with G or C at the third position in codon were favoured against A or T in the S region. There is probably no immune selective pressure to evolve the PS region, while the S region seems to evolve under that pressure.