Bacterial PprI-DdrO system evolved from ImmA-ImmR system in the prophage

Organisms have evolved various response systems to cope with DNA damage, such as the PprI-DdrO system and the ImmA-ImmR system, which mediate the transcription of DNA damage response genes or facilitate the transfer of DNA elements upon sensing DNA damage. The two systems are functionally analogous, and their metalloproteases and regulators are each classified into the same respective protein families, indicating an evolutionary relationship between them. In this article, we analyzed the homology and evolutionary relationship between the ImmA-ImmR and PprI-DdrO. Significant similarities among these proteins were observed through sequence and structure alignments, and the functional association of these protein pairs was confirmed by in silico and biochemical experiments. Furthermore, we revealed a series of protein pairs resembling PprI-DdrO across various species, including ImmA-ImmR from Deinococcus phage elements. Through phylogenetic analysis, we found that these ImmA-ImmR systems share the same major clade with PprI-DdrO. These results revealed a significant association between the PprI-DdrO and ImmA-ImmR systems, inferring that the PprI-DdrO system originated from the ImmA-ImmR system within prophage elements.