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Genome Res. 2015 Jan;25(1):129-41. doi: 10.1101/gr.177543.114. Epub 2014 Sep 18.

Burkholderia pseudomallei sequencing identifies genomic clades with distinct recombination, accessory, and epigenetic profiles.

Author information

1
Genome Institute of Singapore, Singapore, 138672, Republic of Singapore;
2
The Wellcome Trust Sanger Institute, Cambridge, CB10 1SA, United Kingdom;
3
Department of Infectious Disease Epidemiology, Imperial College London, W2 1PG, United Kingdom;
4
Department of Medicine, National University of Singapore, Singapore, 119074 Republic of Singapore;
5
Institute for Glycomics, Griffith University (Gold Coast Campus), Southport, Queensland, QLD 4222, Australia;
6
Pacific Biosciences, Menlo Park, California 94025, USA;
7
Defence Science and Technology Laboratory, Porton Down, Salisbury, SP4 0JQ, United Kingdom;
8
Defense Medical and Environmental Research Institute, DSO National Laboratories, Singapore, 117510, Republic of Singapore;
9
Biosciences, University of Exeter, Exeter, EX4 4QD, United Kingdom;
10
Biosciences, University of Exeter, Exeter, EX4 4QD, United Kingdom; Faculty of Infectious and Tropical Diseases, Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, WC1E 7HT, United Kingdom;
11
Genome Institute of Singapore, Singapore, 138672, Republic of Singapore; Department of Medicine, National University of Singapore, Singapore, 119074 Republic of Singapore;
12
Genome Institute of Singapore, Singapore, 138672, Republic of Singapore; Duke-NUS Graduate Medical School Singapore, Singapore, 169857, Republic of Singapore; Cancer Science Institute of Singapore, National University of Singapore, 117599, Republic of Singapore tanbop@gis.a-star.edu.sg.

Abstract

Burkholderia 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.

PMID:
25236617
PMCID:
PMC4317168
DOI:
10.1101/gr.177543.114
[Indexed for MEDLINE]
Free PMC Article

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