Categorizing Host-Dependent RNA Viruses by Principal Component Analysis of Their Codon Usage Preferences

ABSTRACT Viruses have to exploit host transcription and translation mechanisms to replicate in a hostile host cellular environment, and therefore, it is likely that the infected host may impose pressure on viral evolution. In this study, we investigated differences in codon usage preferences among the highly mutable single strain RNA viruses which infect vertebrate or invertebrate hosts, respectively. We incorporate principal component analysis (PCA) and k-mean methods to clustering viruses infected with different type of hosts. The relative synonymous codon usage (RSCU) indices of all genes in 32 RNA viruses were calculated, and the correlation of the RSCU indices among different viruses was analyzed by the PCA. Our results show a positive correlation in codon usage preferences among viruses that target the same host category. Results of k-means clustering analysis further confirmed the statistical significance of this study, demonstrating that viruses infecting vertebrate hosts have different codon usage preferences to those of invertebrate viruses. Based on the analysis of the effective number of codons (ENC) in relation to the GC-content at the synonymous third codon position (GC3s), we further identified that mutational pressure was the dominant evolution driving force in making the different codon usage preferences. This study suggests a new and effective way to characterize host-dependent RNA viruses based on the codon usage pattern

Clustering of classical swine fever virus isolates by codon pair bias

<p>Abstract</p> <p>Background</p> <p>The genetic code consists of non-random usage of synonymous codons for the same amino acids, termed codon bias or codon usage. Codon juxtaposition is also non-random, referred to as codon context bias or codon pair bias. The codon and codon pair bias vary among different organisms, as well as with viruses. Reasons for these differences are not completely understood. For classical swine fever virus (CSFV), it was suggested that the synonymous codon usage does not significantly influence virulence, but the relationship between variations in codon pair usage and CSFV virulence is unknown. Virulence can be related to the fitness of a virus: Differences in codon pair usage influence genome translation efficiency, which may in turn relate to the fitness of a virus. Accordingly, the potential of the codon pair bias for clustering CSFV isolates into classes of different virulence was investigated.</p> <p>Results</p> <p>The complete genomic sequences encoding the viral polyprotein of 52 different CSFV isolates were analyzed. This included 49 sequences from the GenBank database (NCBI) and three newly sequenced genomes. The codon usage did not differ among isolates of different virulence or genotype. In contrast, a clustering of isolates based on their codon pair bias was observed, clearly discriminating highly virulent isolates and vaccine strains on one side from moderately virulent strains on the other side. However, phylogenetic trees based on the codon pair bias and on the primary nucleotide sequence resulted in a very similar genotype distribution.</p> <p>Conclusion</p> <p>Clustering of CSFV genomes based on their codon pair bias correlate with the genotype rather than with the virulence of the isolates.</p