Genome-wide analysis of codon usage pattern in herpesviruses and its relation to evolution.

The preferential use of a specific codon, out of a group of synonymous codons encoding the same amino acid, in a gene transcript results from the bias in codon choice. Various evolutionary forces namely mutation pressure and natural selection influence the pattern of codon usage i.e. distinct for each gene/genome. We investigated the pattern of codon usage of eight human herpesvirus genomes and compared them with two other herpesvirus genomes namely murine herpesvirus 68 and bovine herpesvirus type 1.1 to elucidate its compositional features, pattern of codon usage across the genomes and report the differences of codon usage pattern of human herpesviruses from that of other two other viruses. We also identified the similarity of the codon usage of human herpesviruses with its host (human). The genes were found to be CG rich in HHV2, HHV3, HHV4, HHV6, HHV7 and BH genomes while TA rich in HHV1, HHV5, HHV8 and MH genomes. The codon usage bias (CUB) of genes was low. A highly significant correlation was found among compositional contents depicting the role of mutational pressure along with natural selection in framing CUB. Several more frequently used codons as well as less frequently used codons were identified to be similar between each human virus and its host (human), while murine herpesvirus 68 and bovine herpesvirus type 1.1 genomes did not possess similar adaptation strategy as human herpesviruses to human (host), thus we could conclude that viral CUB might have been shaped as per their host's nature for better surveillance. Neutrality plot revealed mutational pressure mostly influenced the CUB of HHV1, HHV8 and MH viruses, while natural selection had a major impact in the CUB of HHV2, HHV3, HHV4, HHV5, HHV6, HHV7 and BH genomes.