crAss-like viruses are a putative family of bacteriophages recently discovered. The eponym of the clade, crAssphage, is an enteric bacteriophage estimated to be present in at least half of the human population and it constitutes up to 90% of the sequences in some human fecal viral metagenomic datasets. We focused on the evolutionary dynamics of the genes encoded on the crAssphage genome. By investigating the conservation of the genes, a consistent variation in the evolutionary rates across the different functional groups was found. Gene duplications in crAss-like genomes were detected. By exploring the differences among the functional categories of the genes, we confirmed that the genes encoding capsid proteins were the most ubiquitous, despite their overall low sequence conservation. It was possible to identify a core of proteins whose evolutionary trees strongly correlate with each other, suggesting their genetic interaction. This group includes the capsid proteins, which are thus established as extremely suitable for rebuilding the phylogenetic tree of this viral clade. A negative correlation between the ubiquity and the conservation of viral protein sequences was shown. Together, this study provides an in-depth picture of the evolution of different genes in crAss-like viruses.
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