The interplay of restriction-modification systems with mobile genetic elements and their prokaryotic hosts

Abstract

The roles of restriction-modification (R-M) systems in providing immunity against horizontal gene transfer (HGT) and in stabilizing mobile genetic elements (MGEs) have been much debated. However, few studies have precisely addressed the distribution of these systems in light of HGT, its mechanisms and its vectors. We analyzed the distribution of R-M systems in 2261 prokaryote genomes and found their frequency to be strongly dependent on the presence of MGEs, CRISPR-Cas systems, integrons and natural transformation. Yet R-M systems are rare in plasmids, in prophages and nearly absent from other phages. Their abundance depends on genome size for small genomes where it relates with HGT but saturates at two occurrences per genome. Chromosomal R-M systems might evolve under cycles of purifying and relaxed selection, where sequence conservation depends on the biochemical activity and complexity of the system and total gene loss is frequent. Surprisingly, analysis of 43 pan-genomes suggests that solitary R-M genes rarely arise from the degradation of R-M systems. Solitary genes are transferred by large MGEs, whereas complete systems are more frequently transferred autonomously or in small MGEs. Our results suggest means of testing the roles for R-M systems and their associations with MGEs.

Regulation of genetic flux between bacteria by restriction–modification systems

“…If MGEs targeting bacteria with larger genomes are more abundant, they might lead to strong selection for R-M systems in their bacterial hosts. This might explain why we found more R-M systems in larger genomes (4). It might also explain the positive association between the frequencies of HR and HGT and the abundance of R-M systems (Fig.…”

“…Restriction-modification (R-M) systems are some of the best known and the most widespread bacterial defense systems (4). They encode a methyltransferase (MTase) function that modifies particular DNA sequences in function of the presence of target recognition sites and a restriction endonuclease (REase) function that cleaves them when they are unmethylated (5).…”

Evolutionary Ecology of Prokaryotic Immune Mechanisms

“…Consistent with this idea, RM and CRISPR-Cas systems frequently cooccur (33), and their combination results in increased levels of immunity (110) and more rapid spacer acquisition (111). Moreover, immune mechanisms may even interact synergistically.…”

“…Type IV systems are very different from the others, as they cleave only DNA sequences that have been modified (methylated, hydroxymethylated, or glucosyl-hydroxymethylated) and appear to have evolved independently. Based on the sequence homology, codon usage, and GC content of RM systems, it has been hypothesized that high levels of horizontal gene transfer (HGT) have contributed to the evolution and spread of RM systems (31)(32)(33). The effectiveness of RM systems in host protection against phage infection has been demonstrated in various studies reporting 10-to 10 8 -fold protection against phage infection (reviewed in reference 34).…”

Two novel temperate bacteriophages co-existing in Aeromonas sp. ARM81 – characterization of their genomes, proteomes and DNA methyltransferases

“…Many phage-resistance strategies depend on the use of horizontally acquired 'selfish' elements (plasmids and prophages) that can provide efficient barriers to phage infection (Seed, 2015). Interestingly, orphan MTases were found to be much more abundant in temperate compared with virulent phages, which suggests that such MTases have a rather adaptive role in lysogeny, than protection of their DNA against the restriction endonuclease cleavage (Oliveira et al, 2014).…”