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dc.contributor.authorNandi, Tannistha
dc.contributor.authorHolden, Mathew TG
dc.contributor.authorDidelot, Xavier
dc.contributor.authorMehershahi, Kurosh
dc.contributor.authorBoddey, Justin A
dc.contributor.authorBeacham, Ifor
dc.contributor.authorPeak, Ian
dc.contributor.authorHarting, John
dc.contributor.authorBaybayan, Primo
dc.contributor.authorGuo, Yan
dc.contributor.authorWang, Susana
dc.contributor.authorHow, Lee Chee
dc.contributor.authorSim, Bernice
dc.contributor.authorEssex-Lopresti, Angela
dc.contributor.authorSarkar-Tyson, Mitali
dc.contributor.authorNelson, Michelle
dc.contributor.authorSmither, Sophie
dc.contributor.authorOng, Catherine
dc.contributor.authorAw, Lay Tin
dc.contributor.authorHoon, Chua Hui
dc.contributor.authorMichell, Stephen
dc.contributor.authorStudholme, David J
dc.contributor.authorTitball, Richard
dc.contributor.authorChen, Swaine L
dc.contributor.authorParkhill, Julian
dc.contributor.authorTan, Patrick
dc.date.accessioned2017-05-03T12:19:19Z
dc.date.available2017-05-03T12:19:19Z
dc.date.issued2015
dc.identifier.issn1088-9051
dc.identifier.doi10.1101/gr.177543.114
dc.identifier.urihttp://hdl.handle.net/10072/96796
dc.description.abstractBurkholderia pseudomallei (Bp) is the causative agent of the infectious disease melioidosis. To investigate population diversity, recombination, and horizontal gene transfer in closely related Bp isolates, we performed whole-genome sequencing (WGS) on 106 clinical, animal, and environmental strains from a restricted Asian locale. Whole-genome phylogenies resolved multiple genomic clades of Bp, largely congruent with multilocus sequence typing (MLST). We discovered widespread recombination in the Bp core genome, involving hundreds of regions associated with multiple haplotypes. Highly recombinant regions exhibited functional enrichments that may contribute to virulence. We observed clade-specific patterns of recombination and accessory gene exchange, and provide evidence that this is likely due to ongoing recombination between clade members. Reciprocally, interclade exchanges were rarely observed, suggesting mechanisms restricting gene flow between clades. Interrogation of accessory elements revealed that each clade harbored a distinct complement of restriction-modification (RM) systems, predicted to cause clade-specific patterns of DNA methylation. Using methylome sequencing, we confirmed that representative strains from separate clades indeed exhibit distinct methylation profiles. Finally, using an E. coli system, we demonstrate that Bp RM systems can inhibit uptake of non-self DNA. Our data suggest that RM systems borne on mobile elements, besides preventing foreign DNA invasion, may also contribute to limiting exchanges of genetic material between individuals of the same species. Genomic clades may thus represent functional units of genetic isolation in Bp, modulating intraspecies genetic diversity.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherCold Spring Harbor Laboratory Press
dc.publisher.placeUnited States
dc.relation.ispartofpagefrom129
dc.relation.ispartofpageto141
dc.relation.ispartofissue1
dc.relation.ispartofjournalGenome Research
dc.relation.ispartofvolume25
dc.subject.fieldofresearchBiological sciences
dc.subject.fieldofresearchInfectious agents
dc.subject.fieldofresearchBiomedical and clinical sciences
dc.subject.fieldofresearchMedical bacteriology
dc.subject.fieldofresearchGenetics
dc.subject.fieldofresearchcode31
dc.subject.fieldofresearchcode310702
dc.subject.fieldofresearchcode32
dc.subject.fieldofresearchcode320701
dc.subject.fieldofresearchcode3105
dc.titleBurkholderia pseudomallei Sequencing Identifies Genomic Clades with Distinct Recombination, Accessory and Epigenetic Profiles
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by-nc/4.0/
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2015 Nandi et al.; Published by Cold Spring Harbor Laboratory Press. This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
gro.hasfulltextFull Text
gro.griffith.authorBeacham, Ifor R.
gro.griffith.authorPeak, Ian


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