A Mobile Element in mutS Drives Hypermutation in a Marine Vibrio.
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. 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.



DNA mutations are a double-edged sword. Most mutations are harmful; they can scramble precise genetic sequences honed over thousands of generations. However, in rare cases, mutations also produce beneficial new traits that allow populations to adapt to changing environments. Recent evidence suggests that some bacteria balance this trade-off by altering their mutation rates to suit their environment. To date, however, we know of few mechanisms that allow bacteria to change their mutation rates. We describe one such mechanism, driven by the action of a mobile element, in the marine bacterium Vibrio splendidus 12B01. We also found similar mobile genetic sequences in the mutS genes of many different bacteria, including clinical and agricultural pathogens. These mobile elements might play an as yet unknown role in the evolution of these important bacteria.
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.
Nathaniel D
ND
Chu
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Sean A
SA
Clarke
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Sonia
S
Timberlake
Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Martin F
MF
Polz
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Alan D
AD
Grossman
Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA ejalm@mit.edu.|Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Eric J
EJ
Alm
D059001:Aquatic Organisms / Q000235:genetics*; D020071:Interspersed Repetitive Sequences; D051719:MutS DNA Mismatch-Binding Protein / Q000235:genetics*; D016254:Mutagenesis, Insertional; D059645:Mutation Rate; D011995:Recombination, Genetic; D014733:Vibrio / Q000235:genetics*
D051719:MutS DNA Mismatch-Binding Protein