TY  - JOUR
A1  - Nandi, Tannistha
A1  - Holden, Matthew T.G.
A1  - Didelot, Xavier
A1  - Mehershahi, Kurosh
A1  - Boddey, Justin A.
A1  - Beacham, Ifor
A1  - Peak, Ian
A1  - Harting, John
A1  - Baybayan, Primo
A1  - Guo, Yan
A1  - Wang, Susana
A1  - How, Lee Chee
A1  - Sim, Bernice
A1  - Essex-Lopresti, Angela
A1  - Sarkar-Tyson, Mitali
A1  - Nelson, Michelle
A1  - Smither, Sophie
A1  - Ong, Catherine
A1  - Aw, Lay Tin
A1  - Hoon, Chua Hui
A1  - Michell, Stephen
A1  - Studholme, David J.
A1  - Titball, Richard
A1  - Chen, Swaine L.
A1  - Parkhill, Julian
A1  - Tan, Patrick
T1  - Burkholderia pseudomallei sequencing identifies genomic clades with distinct recombination, accessory, and epigenetic profiles
Y1  - 2015/01/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 129 
EP  - 141 
DO  - 10.1101/gr.177543.114 
VL  - 25 
IS  - 1 
UR  - http://genome.cshlp.org/content/25/1/129.abstract 
N2  - 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. 
ER  -