Viral adaption of staphylococcal phage: A genome-based analysis of the selective preference based on codon usage Bias

Given the high therapeutic value of the staphylococcal phage, the genome co-evolution of the phage and the host has gained great attention. Though the genome-wide AT richness in staphylococcal phages has been well-studied with nucleotide usage bias, here we proved that host factor, lifestyle and taxonomy are also important factors in understanding the phage nucleotide usages bias using information entropy formula. Such correlation is especially prominent when it comes to the synonymous codon usages of staphylococcal phages, despite the overall scattered codon usage pattern represented by principal component analysis. This strong relationship is explained by nucleotide skew which testified that the usage biases of nucleotide at different codon positions are acting on synonymous codons. Therefore, our study reveals a hidden relationship of genome evolution with host limitation and phagic phenotype, providing new insight into phage genome evolution at genetic level.