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

TLDR

Restriction‑modification systems are thought to protect against horizontal gene transfer and stabilize mobile genetic elements, yet their distribution relative to HGT mechanisms and vectors remains poorly understood. The study aims to provide testable approaches to evaluate how restriction‑modification systems interact with mobile genetic elements. Analysis of 2,261 prokaryotic genomes shows that restriction‑modification system frequency is strongly linked to mobile genetic elements, CRISPR‑Cas, integrons, and transformation, is scarce in plasmids and phages, saturates at two per small genome, and that solitary R‑M genes are mainly transferred by large MGEs while complete systems are more often moved autonomously or in small MGEs.

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.