1 SCIENTIFIC REPORTS | (2018) 8:5855 | DOI:10.1038/s41598-018-24034-6 www.nature.com/scientificreports Changing patterns of human migrations shaped the global population structure of Mycobacterium tuberculosis in France Maxime Barbier 1,2 , Oana Dumitrescu 3,4 , Catherine Pichat 4 , Gérard Carret 4 , Anne-Sophie Ronnaux-Baron 5 , Ghislaine Blasquez 5 , Christine Godin-Benhaim 6 , Sandrine Boisset 7,8 , Anne Carricajo 9 , Véronique Jacomo 10 , Isabelle Fredenucci 4 , Michèle Pérouse de Montclos 4 , Charlotte Genestet 3 , Jean-Pierre Flandrois 4,11 , Florence Ader 3,12 , Philip Supply 13 , Gérard Lina 3,4 , Thierry Wirth 1,2 & Jean-Philippe Rasigade 1,2,3,4 Mycobacterium tuberculosis (Mtb) exhibits a structured phylogeographic distribution worldwide linked with human migrations. We sought to infer how the interactions between distinct human populations shape the global population structure of Mtb on a regional scale. We applied the recently described timescaled haplotypic density (THD) technique on 638 minisatellite-based Mtb genotypes from French tuberculosis patients. THD with a long-term (200 y) timescale indicated that Mtb population in France had been mostly infuenced by interactions with Eastern and Southern Europe and, to a lesser extent, Northern and Middle Africa, consistent with historical migrations favored by geographic proximity or commercial exchanges with former French colonies. Restricting the timescale to 20 y, THD identifed a sustained infuence of Northern Africa, but not Europe where tuberculosis incidence decreased sharply. Evolving interactions between human populations, thus, measurably infuence the local population structure of Mtb. Relevant information on such interactions can be inferred using THD from Mtb genotypes. Tuberculosis, one of the oldest diseases known to humanity, is an ongoing public health threat in many low-income countries and a re-emerging disease in several higher-income countries 1–3 . Te causative agent of tuberculosis, Mycobacterium tuberculosis (Mtb), is thought to have co-evolved with modern humans since their expansion out of Africa ~60,000 y ago 4,5 , a situation also encountered in other bacterial pathogens such as Helicobacter pylori 6–8 . Te dispersal of human populations was accompanied with a genetic diversifcation of Mtb into distinct lineages whose current distribution exhibits variable degrees of geographic specifcity 9,10 . Based 1 Institut de Systématique, Evolution, Biodiversité, UMR-CNRS 7205, Muséum National d’Histoire Naturelle, Université Pierre et Marie Curie, Ecole Pratique des Hautes Etudes, Sorbonne Universités, Paris, France. 2 Laboratoire Biologie Intégrative des Populations, Ecole Pratique des Hautes Etudes, PSL Research University, Paris, France. 3 Centre International de Recherche en Infectiologie, CIRI, University of Lyon, Lyon, France. 4 Institut des Agents Infectieux, Hospices Civils de Lyon, Lyon, France. 5 Comité Départemental d’Hygiène Sociale, CLAT69, Lyon, France. 6 Agence Régionale de Santé Auvergne-Rhône-Alpes, Lyon, France. 7 Laboratoire de Bactériologie, Institut de Biologie et de Pathologie, CHU de Grenoble, Grenoble, France. 8 Laboratoire TIMC-IMAG, UMR 5525 CNRS-UJF, UFR de Médecine, Université Grenoble Alpes, Grenoble, France. 9 Laboratoire des Agents Infectieux et d’Hygiène, CHU de Saint-Etienne, Saint-Etienne, France. 10 Laboratoire Biomnis, Lyon, France. 11 Laboratoire de Biométrie et Biologie Evolutive, UMR CNRS 5558, University of Lyon, Lyon, France. 12 Service des Maladies Infectieuses et Tropicales, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France. 13 INSERM U1019, CNRS-UMR 8204, Center for Infection and Immunity of Lille, Institut Pasteur de Lille, Université de Lille, Lille, France. Correspondence and requests for materials should be addressed to J.-P.R. (email: jean-philippe.rasigade@univ-lyon1.fr) Received: 16 August 2017 Accepted: 21 March 2018 Published: xx xx xxxx OPEN