Restriction-Modification Systems as Mobile Epigenetic Elements

Transfer of mobile genetic elements between prokaryotes is limited by restriction-modification systems. Restriction-modification systems consist of a modification enzyme that epigenetically methylates a specific DNA sequence, and a restriction endonuclease (restriction enzyme) that cuts DNA lacking this epigenetic mark. These elements were discovered because they attack mobile genetic elements. However, recent studies have revealed that they are themselves mobile. In some cases, the mobility of restriction-modification systems is through symbiosis with other forms of mobile elements. In other cases, movement is unlinked to other mobile elements. The systems may insert into the genome with long and variable target duplication, or into the intergenic region of an operon. Insertion of restriction-modification systems induces other genome rearrangements such as amplification and inversion. Even a domain within a protein can be the unit of mobility: some restriction-modification system subunits that recognize a target DNA sequence contain mobile amino acid sequences that can apparently move between different domains of a protein through recombination of DNA sequences encoding them. This mobility extends the biological significance of restriction-modification systems beyond defense: the systems define, and sometimes even force, epigenetic order on a genome. The multilevel conflicts involving these mobile epigenetic elements may drive prokaryotic evolution.