Combined Analysis of Variation in Core, Accessory and Regulatory Genome Regions Provides a Super-Resolution View into the Evolution of Bacterial Populations

• Published in: PLoS genetics 2016-09, Vol.12 (9), p.e1006280
• Main Authors: McNally, Alan, Oren, Yaara, Kelly, Darren, Pascoe, Ben, Dunn, Steven, Sreecharan, Tristan, Vehkala, Minna, Välimäki, Niko, Prentice, Michael B, Ashour, Amgad, Avram, Oren, Pupko, Tal, Dobrindt, Ulrich, Literak, Ivan, Guenther, Sebastian, Schaufler, Katharina, Wieler, Lothar H, Zhiyong, Zong, Sheppard, Samuel K, McInerney, James O, Corander, Jukka
• Format: Article
• Language: English
• Subjects: Biology; Biology and Life Sciences; Computer and Information Sciences; Datasets; Drug resistance; Drug Resistance, Microbial - genetics; E coli; Escherichia coli; Escherichia coli - genetics; Escherichia coli - pathogenicity; Escherichia coli Infections - drug therapy; Escherichia coli Infections - genetics; Evolution; Evolution, Molecular; Funding; Gene loci; Genetic aspects; Genetic variation; Genome, Bacterial - drug effects; Genomes; Genomics; Humans; Immunology; Infections; Life sciences; Mathematics; Medicine; Microbial colonies; Observations; Phylogenetics; Phylogeny; Population; Regulatory Sequences, Nucleic Acid - genetics; Research and Analysis Methods; Sequence Analysis, DNA; University colleges
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1006280

The use of whole-genome phylogenetic analysis has revolutionized our understanding of the evolution and spread of many important bacterial pathogens due to the high resolution view it provides. However, the majority of such analyses do not consider the potential role of accessory genes when inferring evolutionary trajectories. Moreover, the recently discovered importance of the switching of gene regulatory elements suggests that an exhaustive analysis, combining information from core and accessory genes with regulatory elements could provide unparalleled detail of the evolution of a bacterial population. Here we demonstrate this principle by applying it to a worldwide multi-host sample of the important pathogenic E. coli lineage ST131. Our approach reveals the existence of multiple circulating subtypes of the major drug-resistant clade of ST131 and provides the first ever population level evidence of core genome substitutions in gene regulatory regions associated with the acquisition and maintenance of different accessory genome elements.