Nucleotide composition and synonymous codon usage of open reading frames in Norovirus GII.4 variants

Abstract

Norovirus GII.4 variants, a genotype in genogroup II belonging to the genus Norovirus, is a single-strand positive sense RNA containing three open reading frames (ORF1, ORF2 and ORF3) and is the most important pathogen causing nonbacterial gastroenteritis outbreaks. By using bioinformatic softwares such as Codon W, SPSS and so on, a total of 292 strains of the viruses isolated from 1974 to 2016 were analyzed for nucleotide composition and synonymous codon usage in each ORF. The result shows that it is enriched for A over the other bases in nucleotide composition, G behind the other bases in the 3^rd site of all synonymous codons in the three ORFs. The patterns of nucleotide composition and codon bias of ORF2 are similar to those of ORF3 and different from those of ORF1. There are generally UpA motif and CpG motif in the codons with the lowest proportion. Correspondence analysis indicates that the codon usage may be changing over a certain time period for ORF1 in 2006 and 2012, ORF2 in 2012, and ORF3 in 2013. ENC (effective number of codons) plot and other analyses indicate that both natural selection and mutational pressure play partly roles in the ORFs, but natural selection is more important for ORF2 and ORF3. Besides, we also found all optimal codons in the ORFs. The study provides a basic understanding of the mechanism for norovirus GII.4 codon usage bias. Abbreviations ORF Open Reading Frame

ENC Effective Number of Codons

COA correspondence analysis

RSCU Relative Synonymous Codon Usage

CAI Codon Adaptation Index

CBI Codon Bias Index

Fop frequency of optimal codons

L_sym number of synonymous codons

L_aa length amino acids

GRAVY grand average of hydropathicity

Aroma aromaticity

Communicated by Ramaswamy H. Sarma