Eukaryotic Association Module in Phage WO Genomes from Wolbachia

Viruses are trifurcated into eukaryotic, archaeal and bacterial categories. This domain-specific ecology underscores why eukaryotic viruses typically co-opt eukaryotic genes and bacteriophages commonly harbor bacterial genes. However, the presence of bacteriophages in obligate intracellular bacteria of eukaryotes may promote DNA transfers between eukaryotes and bacteriophages. Here we report the metagenomic analysis of purified bacteriophage WO particles of Wolbachia and uncover a eukaryotic association module. It encodes domains, such as the black widow latrotoxin C-terminal domain, that are uninterrupted in bacteriophage genomes, enriched with eukaryotic protease cleavage sites, and combined with additional domains to forge one of the largest bacteriophage genes to date (14,256 bp). These domains have never before been reported in packaged bacteriophages, to our knowledge, and their phylogeny, distribution and sequence diversity imply lateral transfers between animal and bacteriophage genomes. Finally, the WO genome sequences and identification of attachment sites will potentially advance genetic manipulation of Wolbachia.