Combined Analysis of Variation in Core, Accessory and Regulatory Genome Regions Provides a Super-Resolution View into the Evolution of Bacterial Populations.
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.
Pathogen Research Group, Nottingham Trent University, Nottingham, United Kingdom.|Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom.
Alan
A
McNally
Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Yaara
Y
Oren
Department of Biology, National University Ireland, Maynooth, Ireland.
Darren
D
Kelly
College of Medicine, University of Swansea, Swansea, United Kingdom.
Ben
0000-0001-6376-5121
B
Pascoe
Pathogen Research Group, Nottingham Trent University, Nottingham, United Kingdom.
Steven
0000-0003-1529-6900
S
Dunn
Pathogen Research Group, Nottingham Trent University, Nottingham, United Kingdom.
Tristan
T
Sreecharan
Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland.
Minna
M
Vehkala
Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland.
Niko
N
Välimäki
Departments of Pathology and Microbiology, University College Cork, Cork, Ireland.
Michael B
MB
Prentice
Departments of Pathology and Microbiology, University College Cork, Cork, Ireland.
Amgad
A
Ashour
Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Oren
O
Avram
Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Tal
T
Pupko
Institute of Hygiene, Universitat Muenster, Muenster, Germany.
Ulrich
0000-0001-9949-1898
U
Dobrindt
Department of Biology and Wildlife Diseases, Faculty of Veterinary Hygiene and Ecology, and CEITEC VFU, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic.
Ivan
I
Literak
Centre for Infection Medicine, Institute of Microbiology and Epizootics, Freie Universitat, Berlin, Germany.
Sebastian
S
Guenther
Centre for Infection Medicine, Institute of Microbiology and Epizootics, Freie Universitat, Berlin, Germany.
Katharina
K
Schaufler
Centre for Infection Medicine, Institute of Microbiology and Epizootics, Freie Universitat, Berlin, Germany.|Robert Koch Institute, Berlin, Germany.
Lothar H
LH
Wieler
Centre for Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China.
Zong
Z
Zhiyong
College of Medicine, University of Swansea, Swansea, United Kingdom.
Samuel K
SK
Sheppard
Department of Biology, National University Ireland, Maynooth, Ireland.|Faculty of Life Sciences, The University of Manchester, Manchester, United Kingdom.
James O
0000-0003-1885-2503
JO
McInerney
Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland.|Department of Biostatistics, University of Oslo, Oslo, Norway.
Jukka
J
Corander
D004352:Drug Resistance, Microbial / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics* / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000235:genetics; D019143:Evolution, Molecular; D016680:Genome, Bacterial / Q000187:drug effects; D006801:Humans; D010802:Phylogeny; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D017422:Sequence Analysis, DNA