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dc.contributor.authorChu, Nathaniel David
dc.contributor.authorClarke, Sean Aidan
dc.contributor.authorTimberlake, Sonia Crago
dc.contributor.authorPolz, Martin F
dc.contributor.authorGrossman, Alan Davis
dc.contributor.authorAlm, Eric J
dc.date.accessioned2017-06-26T17:31:55Z
dc.date.available2017-06-26T17:31:55Z
dc.date.issued2017-02
dc.date.submitted2016-11
dc.identifier.issn2150-7511
dc.identifier.urihttp://hdl.handle.net/1721.1/110261
dc.description.abstractBacteria 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.en_US
dc.description.sponsorshipUnited States. Department of Energy. Office of Biological and Environmental Research (Award no. DE-SC0008743)en_US
dc.language.isoen_US
dc.publisherAmerican Society for Microbiologyen_US
dc.relation.isversionofhttp://dx.doi.org/10.1128/mBio.02045-16en_US
dc.rightsCreative Commons Attribution 4.0 International Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourceAmerican Society for Microbiologyen_US
dc.titleA Mobile Element in mutS Drives Hypermutation in a Marine Vibrioen_US
dc.typeArticleen_US
dc.identifier.citationChu, Nathaniel D., Sean A. Clarke, Sonia Timberlake, Martin F. Polz, Alan D. Grossman, and Eric J. Alm. “A Mobile Element in mutS Drives Hypermutation in a Marine Vibrio.” Edited by Mary Ann Moran. mBio 8, no. 1 (February 7, 2017): e02045–16.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Institute for Medical Engineering & Science
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Civil and Environmental Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Center for Microbiome Informatics and Therapeutics
dc.contributor.mitauthorChu, Nathaniel David
dc.contributor.mitauthorClarke, Sean Aidan
dc.contributor.mitauthorTimberlake, Sonia Crago
dc.contributor.mitauthorPolz, Martin F
dc.contributor.mitauthorGrossman, Alan Davis
dc.contributor.mitauthorAlm, Eric J
dc.relation.journalmBioen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsChu, Nathaniel D.; Clarke, Sean A.; Timberlake, Sonia; Polz, Martin F.; Grossman, Alan D.; Alm, Eric J.en_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0002-7511-5238
dc.identifier.orcidhttps://orcid.org/0000-0001-9296-3733
dc.identifier.orcidhttps://orcid.org/0000-0002-8235-7227
dc.identifier.orcidhttps://orcid.org/0000-0001-8294-9364
mit.licensePUBLISHER_CCen_US


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