RT Journal
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
JF Genome Research 
JO Genome Research 
YR 2015 
FD January 01 
VO 25 
IS 1 
SP 129 
OP 141 
DO 10.1101/gr.177543.114 
UL http://genome.cshlp.org/content/25/1/129.abstract 
AB 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.