Ancestral divergence, genome diversification, and phylogeographic variation in subpopulations of sorbitol-negative, beta-glucuronidase-negative enterohemorrhagic Escherichia coli O157

The O157:H7 lineage of enterohemorrhagic Escherichia coli is a geographical ly disseminated complex of highly related genotypes that share common ances try. The common clone that is found worldwide carries several markers of ev ents in its evolution, including markers for acquisition of virulence genes and loss of physiological characteristics, such as sorbitol fermentation a bility and beta -glucuronidase production. Populations of variants that are distinct with respect to motility and the sorbitol and beta -glucuronidase markers appear to have diverged at several points along the inferred, evol utionary pathway. In addition to these variants, distinct subpopulations of the contemporary non-sorbitol-fermenting, beta -glucuronidase-negative O15 7:H7 clone were recently detected among bovine and human clinical isolates in the United Stares by using high-resolution genome comparison. In order t o determine if these recently described subpopulations were derived from a regional or ancestral divergence event, we used, octamer-based genome scann ing, marker sorting, and DNA sequence analysis to examine their phylogeneti c relationship to populations of non-sorbitol-fermenting, beta -glucuronida se negative O157:H7 and O157:H- strains from Australia. The inferred phylog eny is consistent with the hypothesis that subpopulations on each continent resulted from geographic spread of an ancestral divergence event and subse quent expansion of distinct subpopulations. Marker sorting and DNA sequence analyses identified sets of monophyletic markers consistent with the patte rn of divergence and demonstrated that phylogeographic variation occurred t hrough emergence of regional subclones and concentration of regional polymo rphisms among distinct subpopulations. DNA sequence analysis of representat ive polyphyletic markers showed that genome diversity accrued through rando m drift and bacteriophage-mediated events.