A novel immunity system for bacterial nucleic acid degrading toxins and its recruitment in various eukaryotic and DNA viral systems

Zhang, Dapeng; Iyer, Lakshminarayan M.; Aravind, L.

Implications for eukaryotic and viral functions. Our observations also suggest that the biochemical diversity generated within these bacterial toxin systems has been taken up and utilized for very different functions by eukaryotes and their viruses. Both the SUKH and the SuFu superfamily domains have been utilized as adaptors that regulate recognition of different substrates by protein modification systems such as ubiquitination and polyglutamylation. In a completely different context, the HINT domains derived from such bacterial toxin systems appear to have been used to release peptide messengers in animal signaling pathways, like the hedgehog pathway (70) . The nuclease domains ultimately derived from various toxins also appear to have been used for different functions by eukaryotes and their viruses. The EndoU nuclease domain, which ultimately emerged from these toxin systems, has been recruited by the nidoviruses for the replication of their negative-strand RNA genome, whereas a related domain was recruited by eukaryotes for processing of certain snRNAs. We also observed that a HNH/EndoVII fold nuclease found in the bacterial toxin typified by the N. gonorrhoea protein NGO1392 is found in several eukaryotic lineages such as animals, plants, stramenopiles and apicomplexans (Supplementary Data). Given its conservation and relatively lower divergence, it is unlikely that the nuclease functions as a toxin in eukaryotes. However, it is possible that it has been recruited as a DNA-repair enzyme, as has been previously observed in the case of certain nucleases of bacterial restriction-modification and phage replication systems (97) . In general terms, these observations suggest that the origin of key systems in eukaryotes, including those related to the emergence of certain lineages, such as animals (i.e. the hedgehog pathway), appear to have extensively benefited from the availability of 'pre-adaptations' in the form of components whose ultimate origins lay in these toxin systems.