A detailed comparative analysis on the overall codon usage pattern in herpesviruses

Herpesviruses infect a wide range of organisms including humans. Some of these viruses are potential gene transfer vectors for gene therapy. However no study has been reported on total codon usage of herpesvirus. In this study, the patterns of synonymous codon usage in herpesviruses have been studied through multivariate statistical methods on 4875 ORFs from the available 49 completely sequenced herpesvirus genomes. A general trend of weakly biased codon usage was observed among herpesviruses, but few among them showed some degree of strong bias. The principal determinants behind such notable variations within the patterns seemed to be the overall GC content and GC content at the 3rd base position of the viral genes. These determinants strongly correlated with the first major axis of correspondence analysis on relative synonymous codon usage (RSCU). This is an indication of mutational bias that dominates over translational selection in herpesvirus. Among the other determining factors, gene length also has some degree of influence on the codon usage pattern. The comparative analysis of the preferred and optimal codons among the clades revealed that different codons were preferred in different clades, though six codons CUG, CAC, CAG, AAC, GUG, and GAC were found to be more frequent in most of the herpesviral genes. Codon adaptation index (CAI) was used to predict highly expressed genes among herpesviruses, and to identify translationally optimal codons. Cluster analysis reveals that the majority of the members of a clade have similar codon usage and nucleotide composition, but with some notable exception. Additionally phylogenetic analysis indicates that codon usage of the viruses cannot be explicitly tied to their species evolution.