Codon bias is a major factor explaining phage evolution in translationally biased hosts

The size and diversity of bacteriophage populations require methodologies to quantitatively study the landscape of phage differences. Statistical approaches are confronted with small genome sizes forbidding significant single-phage analysis, and comparative methods analyzing full phage genomes represent an alternative but they are of difficult interpretation due to lateral gene transfer, which creates a mosaic spectrum of related phage species. Based on a large-scale codon bias analysis of 116 DNA phages hosted by 11 translationally biased bacteria belonging to different phylogenetic families, we observe that phage genomes are almost always under codon selective pressure imposed by translationally biased hosts, and we propose a classification of phages with translationally biased hosts which is based on adaptation patterns. We introduce a computational method for comparing phages sharing homologous proteins, possibly accepted by different hosts. We observe that throughout phages, independently from the host, capsid genes appear to be the most affected by host translational bias. For coliphages, genes involved in virion morphogenesis, host interaction and ssDNA binding are also affected by adaptive pressure. Adaptation affects long and small phages in a significant way. We analyze in more detail the Microviridae phage space to illustrate the potentiality of the approach. The small number of directions in adaptation observed in phages grouped around phi X174 is discussed in the light of functional bias. The adaptation analysis of the set of Microviridae phages defined around phi MH2K shows that phage classification based on adaptation does not reflect bacterial phylogeny.