Eukaryotic Association Module in Phage WO Genomes from Wolbachia

Abstract

Viruses are trifurcated into eukaryotic, archaeal and bacterial categories. This domain-specific ecology underscores why eukaryotic genes are typically co-opted by eukaryotic viruses and bacterial genes are commonly found in bacteriophages. However, the presence of bacteriophages in symbiotic bacteria that obligately reside in eukaryotes may promote eukayotic DNA transfers to bacteriophages. By sequencing full genomes from purified bacteriophage WO particles of Wolbachia, we discover a novel eukaryotic association module with various animal proteins domains, such as the black widow latrotoxin-CTD, that are uninterrupted in intact bacteriophage genomes, enriched with eukaryotic protease cleavage sites, and combined with additional domains to forge some of the largest bacteriophage genes (up to 14,256 bp). These various protein domain families are central to eukaryotic functions and have never before been reported in packaged bacteriophages, and their phylogeny, distribution and sequence diversity implies lateral transfer from animal to bacteriophage genomes. We suggest that the evolution of these eukaryotic protein domains in bacteriophage WO parallels the evolution of eukaryotic genes in canonical eukaryotic viruses, namely those commandeered for viral life cycle adaptations. Analogous selective pressures and evolutionary outcomes may occur in bacteriophage WO as a result of its \"two-fold cell challenge\" to persist in and traverse cells of obligate intracellular bacteria that strictly reside in animal cells. Finally, the full WO genome sequences and identification of attachment sites will advance eventual genetic manipulation of Wolbachia for disease control strategies.