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.

Eukaryotic/DNA viral members and structure-function analysis of the SUKH superfamily While SUKH superfamily neighborhoods are very widespread in bacteria, they are largely absent in archaea. Although we uncovered potential extruded nuclease toxins in certain halophilic archaea such as H. borinquense (gi: 312291883, with a GH-E nuclease domain), which are delivered by means of a distinctive N-terminal metallopeptidase domain, we did not find any immunity proteins of the SUKH or SuFu superfamilies. Although the exact reason for this exclusion is unclear, it is conceivable that these immunity proteins are ineffective in the context of the distinct archaeal secretory systems. However, several eukaryotes possess one or more SUKH superfamily members. Phylogenetic analysis and phyletic patterns suggest that there are two major eukaryotic lineages of the SUKH superfamily that are nested within the radiation of the bacterial versions (Supplementary Data). They are respectively prototyped by the polyglutamylase subunit PGs2 (22) , and the vertebrate SCF ubiquitin E3 ligase subunit FBXO3 with yeast Smi1/Knr4 (21, 73) . The PGs2 version is found in basal eukaryotes such as Giardia and Spironucleus, animals and chlorophyte algae suggesting that it was likely to have been acquired prior to the last eukaryotic common ancestor (LECA) and subsequently lost in several lineages. The FBXO3 lineage is present in animals, fungi, plants, stramenopiles and ciliates. However, it does not group with the PGs2 lineage, instead grouping with other bacterial forms. Hence, it was probably acquired relatively early in eukaryotic evolution via an independent transfer from bacteria. In both plants and animals the FBXO3 version is fused to an N-terminal F-box domain and a distinctive C-terminal immunoglobulin superfamily domain (overlaps with the PFAM model DUF525), suggesting that it was recruited as an E3 subunit prior to the radiation of these eukaryotic groups. In addition to these versions, there appear to have been other sporadic transfers of SUKH superfamily members to eukaryotes. For example, land plants contain a version typified by the Arabidopsis protein At3g50340 (gi: 15229727) which seems to have been independently acquired by them from a bacterial source. Another sporadic transfer is seen in certain filamentous fungi, which acquired a version of the SUKH-4 group that has been independently fused to an N-terminal F-box domain (e.g. A. oryzae gi: 169782758). DNA viral versions show no specific relationship with eukaryotic forms; instead, they share specific sequence motifs with the SUKH-3 group, recover them as best hits in profile-profile comparisons, and group with them in the phylogenetic tree (Supplementary Data). Within viruses they are most widespread and abundant in herpesviruses, with the versions from adenoviruses, poxviruses and iridoviruses being nested within the herpesviral radiation of the family (Supplementary Data). Thus, they appear to have been acquired first by an ancestral herpesvirus, similar to that inserted in the amphioxus genome (46) , from a bacterial source and subsequently disseminated across diverse DNA viruses.