title: Long-range dispersal movedFrancisella tularensisinto Western Europe from the East.
abstract: For many infections transmitting to humans from reservoirs in nature, disease dispersal patterns over space and time are largely unknown. Here, a reversed genomics approach helped us understand disease dispersal and yielded insight into evolution and biological properties ofFrancisella tularensis, the bacterium causing tularemia. We whole-genome sequenced 67 strains and characterized by single-nucleotide polymorphism assays 138 strains, collected from individuals infected 1947-2012 across Western Europe. We used the data for phylogenetic, population genetic and geographical network analyses. All strains (n=205) belonged to a monophyletic population of recent ancestry not found outside Western Europe. Most strains (n=195) throughout the study area were assigned to a star-like phylogenetic pattern indicating that colonization of Western Europe occurred via clonal expansion. In the East of the study area, strains were more diverse, consistent with a founder population spreading from east to west. The relationship of genetic and geographic distance within theF. tularensispopulation was complex and indicated multiple long-distance dispersal events. Mutation rate estimates based on year of isolation indicated null rates; in outbreak hotspots only, there was a rate of 0.4 mutations/genome/year. Patterns of nucleotide substitution showed marked AT mutational bias suggestive of genetic drift. These results demonstrate that tularemia has moved from east to west in Europe and thatF. tularensishas a biology characterized by long-range geographical dispersal events and mostly slow, but variable, replication rates. The results indicate that mutation-driven evolution, a resting survival phase, genetic drift and long-distance geographical dispersal events have interacted to generate genetic diversity within this species.
authors.affiliation: 1​Department of Clinical Microbiology and the Laboratory for Molecular Infection Medicine Sweden, Umeå University, Umeå, Sweden.|2​Division of CBRN Security and Defence, Swedish Defense Research Agency, Umeå, Sweden.
authors.forename: Chinmay
authors.initials: C
authors.lastname: Dwibedi
authors.affiliation: 3​Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff AZ, USA.
authors.forename: Dawn
authors.initials: D
authors.lastname: Birdsell
authors.affiliation: 2​Division of CBRN Security and Defence, Swedish Defense Research Agency, Umeå, Sweden.
authors.forename: Adrian
authors.initials: A
authors.lastname: Lärkeryd
authors.affiliation: 2​Division of CBRN Security and Defence, Swedish Defense Research Agency, Umeå, Sweden.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Myrtennäs
authors.affiliation: 2​Division of CBRN Security and Defence, Swedish Defense Research Agency, Umeå, Sweden.
authors.forename: Caroline
authors.initials: C
authors.lastname: Öhrman
authors.affiliation: 2​Division of CBRN Security and Defence, Swedish Defense Research Agency, Umeå, Sweden.
authors.forename: Elin
authors.initials: E
authors.lastname: Nilsson
authors.affiliation: 2​Division of CBRN Security and Defence, Swedish Defense Research Agency, Umeå, Sweden.
authors.forename: Edvin
authors.initials: E
authors.lastname: Karlsson
authors.affiliation: 3​Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff AZ, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Hochhalter
authors.affiliation: 3​Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff AZ, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Rivera
authors.affiliation: 3​Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff AZ, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Maltinsky
authors.affiliation: 3​Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff AZ, USA.
authors.forename: Brittany
authors.initials: B
authors.lastname: Bayer
authors.affiliation: 3​Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff AZ, USA.|4​Translational Genomics Research Institute North, Flagstaff AZ, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Keim
authors.affiliation: 5​Bundeswehr Institute of Microbiology, Munich, Germany.
authors.forename: Holger C
authors.initials: HC
authors.lastname: Scholz
authors.affiliation: 6​Institute of Bacterial Infections and Zoonoses Friedrich-Loeffler, Institut Federal Research Institute for Animal Health, Jena, Germany.
authors.forename: Herbert
authors.initials: H
authors.lastname: Tomaso
authors.affiliation: 7​Biology Division, Spietz Laboratory, Federal Office for Civil Protection, Spietz, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Wittwer
authors.affiliation: 7​Biology Division, Spietz Laboratory, Federal Office for Civil Protection, Spietz, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Beuret
authors.affiliation: 7​Biology Division, Spietz Laboratory, Federal Office for Civil Protection, Spietz, Switzerland.
authors.forename: Nadia
authors.initials: N
authors.lastname: Schuerch
authors.affiliation: 8​Institute of Veterinary Bacteriology, University of Bern, Bern, Switzerland.
authors.forename: Paola
authors.initials: P
authors.lastname: Pilo
authors.affiliation: 9​Laboratory of Molecular Biology and Microbiology, Instituto Tecnológico Agrario de Castilla y León, Valladolid, Spain.|10​Departamento de Ingeniería Agrícola y Forestal, Universidad de Valladolid, Palencia, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Hernández Pérez
authors.affiliation: 11​Department of Biotechnology and Food science, Universidad de Burgos, Burgos, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Rodriguez-Lazaro
authors.affiliation: 12​Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Escudero
authors.affiliation: 12​Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Anda
authors.affiliation: 2​Division of CBRN Security and Defence, Swedish Defense Research Agency, Umeå, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Forsman
authors.affiliation: 3​Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff AZ, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Wagner
authors.affiliation: 2​Division of CBRN Security and Defence, Swedish Defense Research Agency, Umeå, Sweden.
authors.forename: Pär
authors.initials: P
authors.lastname: Larsson
authors.affiliation: 1​Department of Clinical Microbiology and the Laboratory for Molecular Infection Medicine Sweden, Umeå University, Umeå, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Johansson
mesh_terms: D004269:DNA, Bacterial / Q000235:genetics; D005060:Europe; D019143:Evolution, Molecular; D005604:Francisella tularensis / Q000145:classification* / Q000502:physiology*; D005828:Genetics, Population; D006801:Humans; D009154:Mutation; D010802:Phylogeny; D014406:Tularemia / Q000382:microbiology
chemical_list: D004269:DNA, Bacterial
keywords: Francisella tularensis; disease transmission; epidemiology; genetic variation; human; population genetics