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Title: A Mobile Element in mutS Drives Hypermutation in a Marine Vibrio

Journal Article · · mBio
 [1];  [2];  [2];  [3];  [4];  [5];
  1. Microbiology Graduate Program, Microbiology Graduate Program, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA, Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
  2. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
  3. Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
  4. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
  5. Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA, Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

Bacteria face a trade-off between genetic fidelity, which reduces deleterious mistakes in the genome, and genetic innovation, which allows organisms to adapt. Evidence suggests that many bacteria balance this trade-off by modulating their mutation rates, but few mechanisms have been described for such modulation. Following experimental evolution and whole-genome resequencing of the marine bacterium Vibrio splendidus 12B01, we discovered one such mechanism, which allows this bacterium to switch to an elevated mutation rate. This switch is driven by the excision of a mobile element residing in mutS, which encodes a DNA mismatch repair protein. When integrated within the bacterial genome, the mobile element provides independent promoter and translation start sequences for mutS—different from the bacterium’s original mutS promoter region—which allow the bacterium to make a functional mutS gene product. Excision of this mobile element rejoins the mutS gene with host promoter and translation start sequences but leaves a 2-bp deletion in the mutS sequence, resulting in a frameshift and a hypermutator phenotype. We further identified hundreds of clinical and environmental bacteria across Betaproteobacteria and Gammaproteobacteria that possess putative mobile elements within the same amino acid motif in mutS. In a subset of these bacteria, we detected excision of the element but not a frameshift mutation; the mobile elements leave an intact mutS coding sequence after excision. Finally, our findings reveal a novel mechanism by which one bacterium alters its mutation rate and hint at a possible evolutionary role for mobile elements within mutS in other bacteria.

Research Organization:
Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)
Sponsoring Organization:
USDOE Office of Science (SC)
Grant/Contract Number:
SC0008743
OSTI ID:
1617746
Alternate ID(s):
OSTI ID: 1366724
Journal Information:
mBio, Journal Name: mBio Vol. 8 Journal Issue: 1; ISSN 2161-2129
Publisher:
American Society for MicrobiologyCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 15 works
Citation information provided by
Web of Science

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