Analysis of Compositional Biasness in the Y-domain of Hepatitis E Viruses

Hepatitis E virus (HEV) of the family Hepeviridae is a positive-sense, single-stranded RNA virus. The HEV genome constitutes three open-reading frames (ORFs): ORF1 ORF2 and ORF3. The 5’ most non-structural ORF1 consists of multiple functional domains responsible for the replication of HEV. The ORFI Y-domain region (YDR) codon usage analysis has not been explored. Thus, we aimed to analyze the codon usage features to characterize YDR role in the molecular evolution of HEV. The nucleotide composition analysis indicated that YDR genome was richly endowed with C and U nucleotides. Relative synonymous codon usage (RSCU) analysis results revealed biasness towards U- and C-ended codons over A- and G- ended codons among genotypes 3 and 4. However, C- and U-ended codons were preferred across genotype 1 sequences. Thus, our data indicates that codon bias of genotype 1 of HEV YDR was significantly different from those of genotypes 3 and 4 which suggested U/C richness. Our findings further emphasised that both mutational and selection forces constrained the codon usage in YDR. To the best of our knowledge, our study is the first attempt to delineate the genotype-specific codon usage patterns of YDR genomes. The findings are envisaged to augment our understanding of factors in the evolution of HEV.