Compositional Biasness in the Open Reading Frame 4 of Hepatitis E Viruses

The open reading frame 4 (ORF4) constitutes an important component of the genome of the Hepatitis E virus (HEV) Genotype 1 (GT 1). The codon usage is involved in establishing a host-pathogen relationship, therefore, in this context, different factors influencing the codon usage patterns were analyzed in the ORF4 coding sequences of HEV. The overall nucleotide composition showed C as the most-represented nucleotide and A as the least in the ORF4 coding sequences. Relative synonymous codon usage (RSCU) revealed biasness towards C and G-ended codons over U and A-ended codons. GC content was significantly higher in ORF4 coding genes. The comparative codon frequency analysis among HEV-hosts showed both similarities and differences in preferred codon usage signifying that ORF4 codon usage patterns were a mixture of coincidence and antagonism. Further, our results emphasized the influence of both selection forces, i.e., mutational pressure and natural selection, on the codon usage patterns of ORF4, from virus and host respectively. The present study highlighted the influence of compositional constraints, codon usage biasness, in conjunction with the selective forces in shaping the ORF4 codon usage patterns. These findings are expected to increase our understanding of factors involved in viral evolution, and fitness towards hosts and the environment.