Single-stranded genomic architecture constrains optimal codon usage

Abstract

Viral codon usage is shaped by the conflicting forces of mutational pressure and selection to match host patterns for optimal expression. We examined whether genomic architecture (single- or double-stranded DNA) influences the degree to which bacteriophage codon usage differ from their primary bacterial hosts and each other. While both correlated equally with their hosts' genomic nucleotide content, the coat genes of ssDNA phages were less well adapted than those of dsDNA phages to their hosts' codon usage profiles due to their preference for codons ending in thymine. No specific biases were detected in dsDNA phage genomes. In all nine of ten cases of codon redundancy in which a specific codon was overrepresented, ssDNA phages favored the NNT codon. A cytosine to thymine biased mutational pressure working in conjunction with strong selection against non-synonymous mutations appears be shaping codon usage bias in ssDNA viral genomes.

Figure 1. Correlation between host and phage genomic GC content. Grey squares indicate dsDNA phages, open squares ssDNA. Best-fit linear regression lines are solid for dsDNA (r² = 0.84) and dashed for ssDNA (r² = 0.82). There was no significant difference between the correlations (p = 0.72).

Figure 2. Mean coat gene CAI with 95% confidence intervals of ssDNA (n = 11), dsDNA (n = 34) coliphages.

Figure 3. GC1,2/GC3 correlation for ssDNA (open squares) and dsDNA (gray squares) coliphage coat genes. Solid line indicates perfect correlation. Points above the line indicate genes deficient in GC3, points below denote genes enriched in GC3.

Figure 4. Mean RSCU values and 95% confidence intervals for individual codons with statistically significant differences in usage between ssDNA (open squares) and dsDNA (gray squares) coliphage coat or tail genes.

Figure 5. RSCU values and 95% confidence intervals for ssDNA phage coat gene codons that exhibited an NNT codon preference. Preferred NNT codons indicated by bold triangles, NNV codons indicated by squares.