Behavior of restriction-modification systems as selfish mobile elements and their impact on genome evolution

Abstract

Restriction-modification (RM) systems are composed of genes that encode a restriction enzyme and a modification methylase. RM systems sometimes behave as discrete units of life, like viruses and transposons. RM complexes attack invading DNA that has not been properly modified and thus may serve as a tool of defense for bacterial cells. However, any threat to their maintenance, such as a challenge by a competing genetic element (an incompatible plasmid or an allelic homologous stretch of DNA, for example) can lead to cell death through restriction breakage in the genome. This post-segregational or post-disturbance cell killing may provide the RM complexes (and any DNA linked with them) with a competitive advantage. There is evidence that they have undergone extensive horizontal transfer between genomes, as inferred from their sequence homology, codon usage bias and GC content difference. They are often linked with mobile genetic elements such as plasmids, viruses, transposons and integrons. The comparison of closely related bacterial genomes also suggests that, at times, RM genes themselves behave as mobile elements and cause genome rearrangements. Indeed some bacterial genomes that survived post-disturbance attack by an RM gene complex in the laboratory have experienced genome rearrangements. The avoidance of some restriction sites by bacterial genomes may result from selection by past restriction attacks. Both bacteriophages and bacteria also appear to use homologous recombination to cope with the selfish behavior of RM systems. RM systems compete with each other in several ways. One is competition for recognition sequences in post-segregational killing. Another is super-infection exclusion, that is, the killing of the cell carrying an RM system when it is infected with another RM system of the same regulatory specificity but of a different sequence specificity. The capacity of RM systems to act as selfish, mobile genetic elements may underlie the structure and function of RM enzymes.

Diverse Functions of Restriction-Modification Systems in Addition to Cellular Defense

“…Despite their function in cellular defense, these gene complexes tend to propagate as selfish elements to promote their own survival and increase their relative frequency (28,41,88). For example, the failure to segregate R-M-encoding plasmids equally during cell division results in cell death for the progeny lacking these plasmids (28,89).…”

Genomics of DNA cytosine methylation in Escherichia coli reveals its role in stationary phase transcription

“…In bacteria, methylation is best studied as part of restriction-modification (R-M) systems that have long been considered as contributing to bacterial immune response against incoming DNA including phages 4 . However, recent research has suggested that R-M systems may be 'selfish' elements that protect themselves against removal, through post-segregational killing of newly born progeny by pre-existing and stable restriction enzyme molecules [5][6][7][8][9][10][11] .…”

Maintenance Forced by a Restriction-Modification System Can Be Modulated by a Region in Its Modification Enzyme Not Essential for Methyltransferase Activity

“…A third type of postsegregational killing systems consists of several type II restriction-modification (RM) systems (29,31,48). A type II RM system is typically composed of a gene encoding a DNA endonuclease (restriction enzyme), which cleaves double-stranded DNA at a specific recognition sequence, and a gene encoding a DNA methyltransferase (modification enzyme), which methylates the same recognition sequence to protect DNA from the cleavage.…”

“…Analyses of various prokaryotic genomes provide evidence that RM genes move between prokaryotic genomes (29,31). In fact, RM genes are often found on mobile genetic elements such as plasmids, viruses, transposons, and integrons (56).…”

“…Comparison of closely related bacterial genomes also suggests that RM genes themselves behave as mobile elements and cause genome rearrangements (2,7,50). Therefore, we proposed a hypothesis that several type II RM gene systems represent selfish genetic elements, the so-called selfish-gene hypothesis (29,31,48). Their attack on invading DNA is not exclusive to their selfish nature; the host genome and the RM systems have a common interest when they encounter such an invasion.…”