A family of phase-variable restriction enzymes with differing specificities generated by high-frequency gene rearrangements

Kevin Dybvig, Ramakrishnan Sitaraman, C. Todd French

Research output: Contribution to journalArticlepeer-review

105 Scopus citations

Abstract

The hsd genes of Mycoplasma pulmonis encode restriction and modification enzymes exhibiting a high degree of sequence similarity to the type I enzymes of enteric bacteria. The S subunits of type I systems dictate the DNA sequence specificity of the holoenzyme and are required for both the restriction and the modification reactions. The M. pulmonis chromosome has two hsd loci, both of which contain two hsdS genes each and are complex, site-specific DNA inversion systems. Embedded within the coding region of each hsdS gene are a minimum of three sites at which DNA inversions occur to generate extensive amino acid sequence variations in the predicted S subunits. We show that the polymorphic hsdS genes produced by gene rearrangement encode a family of functional S subunits with differing DNA sequence specificities. In addition to creating polymorphisms in hsdS sequences, DNA inversions regulate the phase-variable production of restriction activity because the other genes required for restriction activity (hsdR and hsdM) are expressed only from loci that are oriented appropriately in the chromosome relative to the hsd promoter. These data cast doubt on the prevailing paradigms that restriction systems are either selfish or function to confer protection from invasion by foreign DNA.

Original languageEnglish (US)
Pages (from-to)13923-13928
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number23
DOIs
StatePublished - Nov 10 1998
Externally publishedYes

Keywords

  • Antigenic variation
  • DNA inversion
  • Mycoplasma virus
  • Mycoplasmas
  • Phase variation

ASJC Scopus subject areas

  • General

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