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

Area of Science:

• Molecular Biology
• Genomics
• Biochemistry

Background:

• Phosphorothioate (PT) DNA modification involves replacing a nonbridging oxygen with sulfur in the DNA backbone.
• PT modification, catalyzed by DndABCDE proteins and recognized by DndFGH enzymes, forms a bacterial restriction-modification (R-M) system.

Purpose of the Study:

• To investigate the prevalence and diverse functions of bacterial dnd systems beyond their known R-M roles.
• To explore the non-R-M functions of solitary PT modification in bacterial physiology.

Main Methods:

• Genomic survey to identify dnd system distribution across bacterial phyla.
• Phylogenetic analysis of PT R-M pairs to understand their evolutionary history.
• Epigenomic, transcriptomic, and metabolomic analyses to assess the physiological impact of PT modification.

Main Results:

• Identified 1,349 bacterial dnd systems, with nearly half lacking restriction enzyme counterparts.
• Phylogenetic analysis indicated coevolution of methyltransferase and restriction enzyme components, with evidence of horizontal gene transfer.
• Solitary PT modification impacts cellular redox state and epigenetic regulation, altering gene expression and metabolic pathways in Pseudomonas fluorescens.

Conclusions:

• PT DNA modification exhibits versatility beyond its established role in bacterial R-M systems.
• Solitary PT modification plays a significant role in maintaining cellular redox homeostasis and epigenetic control.
• The widespread distribution of dnd systems suggests diverse, yet to be fully understood, biological functions.