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Burkholderia pseudomallei sequencing identifies genomic clades with distinct
recombination, accessory, and epigenetic profiles
#MMPMID25236617
Nandi T
; Holden MT
; Didelot X
; Mehershahi K
; Boddey JA
; Beacham I
; Peak I
; Harting J
; Baybayan P
; Guo Y
; Wang S
; How LC
; Sim B
; Essex-Lopresti A
; Sarkar-Tyson M
; Nelson M
; Smither S
; Ong C
; Aw LT
; Hoon CH
; Michell S
; Studholme DJ
; Titball R
; Chen SL
; Parkhill J
; Tan P
Genome Res
2015[Jan]; 25
(1
): 129-41
PMID25236617
show ga
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.
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