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Authors: Nandi, Tannistha and Holden, Mathew T G and Didelot, Xavier and Mehershahi, Kurosh and Boddey, Justin A and Beacham, Ifor and Peak, Ian and Harting, John and Baybayan, Primo and Guo, Yan and Wang, Susana and How, Lee Chee and Sim, Bernice and Essex-Lopresti, Angela and Sarkar-Tyson, Mitali and Nelson, Michelle and Smither, Sophie and Ong, Catherine and Aw, Lay Tin and Hoon, Chua Hui and Michell, Stephen and Studholme, David J and Titball, Richard and Chen, Swaine L and Parkhill, Julian and Tan, Patrick

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. © 2015 Nandi et al.; Published by Cold Spring Harbor Laboratory Press.

Journal: Genome research
DOI: 10.1101/gr.177543.114
Year: 2015

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