Occurrence, evolution, and functions of DNA phosphorothioate epigenetics in bacteria

Significance Phosphorothioate (PT) modification of the DNA sugar-phosphate backbone is an important microbial epigenetic modification governed by DndABCDE, which together with DndFGH, constitutes a restriction-modification system. We show that up to 45% of 1,349 identified bacterial dnd systems exhibit the form of solitary dndABCDE without the restriction counterparts of dndFGH . The combination of epigenomics, transcriptome analysis, and metabolomics suggests that in addition to providing a genetic barrier against invasive DNA, PT modification is a versatile player involved in the epigenetic control of gene expression and the maintenance of cellular redox homeostasis. This finding provides evolutionary and functional insights into this unusual epigenetic modification. Our results imply that PT systems might evolve similar to other epigenetic modification systems with multiple cellular functions.