Cold Spring Harbor Laboratory Press, Genome Research, 1(25), p. 129-141, 2014
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Burkholderia pseudomallei (Bp) is the causative agent of melioidosis, a serious infectious disease of human and animals. 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 phylogeny resolved multiple genomic clades of Bp largely congruent with multi-locus 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 which may contribute to virulence. We observed striking clade-specific patterns of recombination and accessory gene exchange, and provide evidence that this is likely due to ongoing recombination between clade members. Reciprocally, inter-clade 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 whole-genome methylome sequencing, we confirmed that representative strains from separate clades indeed exhibit distinct methylation profiles. Finally, using an E. coli experimental system, we demonstrate that Bp RM systems can inhibit uptake of non-self DNA. Our data suggests that RM systems on mobile elements, besides preventing invasion of foreign DNA, may also contribute to limit the exchange of genes and gene variants between individuals of the same species. Genomic clades may thus represent functional units of genetic isolation in Bp, modulating intra-species genetic diversity.