title: Population Genomics of Mycobacterium tuberculosis in Ethiopia Contradicts the Virgin Soil Hypothesis for Human Tuberculosis in Sub-Saharan Africa.
abstract: Colonial medical reports claimed that tuberculosis (TB) was largely unknown in Africa prior to European contact, providing a "virgin soil" for spread of TB in highly susceptible populations previously unexposed to the disease [1, 2]. This is in direct contrast to recent phylogenetic models which support an African origin for TB [3-6]. To address this apparent contradiction, we performed a broad genomic sampling of Mycobacterium tuberculosis in Ethiopia. All members of the M. tuberculosis complex (MTBC) arose from clonal expansion of a single common ancestor [7] with a proposed origin in East Africa [3, 4, 8]. Consistent with this proposal, MTBC lineage 7 is almost exclusively found in that region [9-11]. Although a detailed medical history of Ethiopia supports the view that TB was rare until the 20(th) century [12], over the last century Ethiopia has become a high-burden TB country [13]. Our results provide further support for an African origin for TB, with some genotypes already present on the continent well before European contact. Phylogenetic analyses reveal a pattern of serial introductions of multiple genotypes into Ethiopia in association with human migration and trade. In place of a "virgin soil" fostering the spread of TB in a previously naive population, we propose that increased TB mortality in Africa was driven by the introduction of European strains of M. tuberculosis alongside expansion of selected indigenous strains having biological characteristics that carry a fitness benefit in the urbanized settings of post-colonial Africa.
authors.affiliation: Genomics and Health Unit, FISABIO Public Health, Valencia 46020, Spain; CIBER (Centros de Investigación Biomédica en Red) in Epidemiology and Public Health, Instituto de Salud Carlos III, Madrid 28029, Spain. Electronic address: inaki.comas@uv.es.
authors.forename: Iñaki
authors.initials: I
authors.lastname: Comas
authors.affiliation: Armauer Hansen Research Institute, PO Box 1005, Addis Ababa, Ethiopia.
authors.forename: Elena
authors.initials: E
authors.lastname: Hailu
authors.affiliation: Armauer Hansen Research Institute, PO Box 1005, Addis Ababa, Ethiopia.
authors.forename: Teklu
authors.initials: T
authors.lastname: Kiros
authors.affiliation: Armauer Hansen Research Institute, PO Box 1005, Addis Ababa, Ethiopia.
authors.forename: Shiferaw
authors.initials: S
authors.lastname: Bekele
authors.affiliation: Armauer Hansen Research Institute, PO Box 1005, Addis Ababa, Ethiopia.
authors.forename: Wondale
authors.initials: W
authors.lastname: Mekonnen
authors.affiliation: Armauer Hansen Research Institute, PO Box 1005, Addis Ababa, Ethiopia.
authors.forename: Balako
authors.initials: B
authors.lastname: Gumi
authors.affiliation: Armauer Hansen Research Institute, PO Box 1005, Addis Ababa, Ethiopia; Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel 4002, and University of Basel, Basel 4003, Switzerland.
authors.forename: Rea
authors.initials: R
authors.lastname: Tschopp
authors.affiliation: Aklilu Lemma Institute of Pathobiology, Addis Ababa University, PO Box 1176, Addis Ababa, Ethiopia.
authors.forename: Gobena
authors.initials: G
authors.lastname: Ameni
authors.affiliation: Bovine TB Research Group, Animal and Plant Health Agency, Surrey KT15 3NB, UK.
authors.forename: R Glyn
authors.initials: RG
authors.lastname: Hewinson
authors.affiliation: Center for Molecular Bacteriology and Infection, Department of Medicine, Flowers Building, South Kensington, Imperial College London, London SW7 2AZ, UK.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Robertson
authors.affiliation: Genomics and Health Unit, FISABIO Public Health, Valencia 46020, Spain.
authors.forename: Galo A
authors.initials: GA
authors.lastname: Goig
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel 4002, and University of Basel, Basel 4003, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Stucki
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel 4002, and University of Basel, Basel 4003, Switzerland.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Gagneux
authors.affiliation: Armauer Hansen Research Institute, PO Box 1005, Addis Ababa, Ethiopia.
authors.forename: Abraham
authors.initials: A
authors.lastname: Aseffa
authors.affiliation: The Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Douglas
authors.initials: D
authors.lastname: Young
authors.affiliation: Bovine TB Research Group, Animal and Plant Health Agency, Surrey KT15 3NB, UK. Electronic address: stefan.berg@apha.gsi.gov.uk.
authors.forename: Stefan
authors.initials: S
authors.lastname: Berg
mesh_terms: D005002:Ethiopia / Q000453:epidemiology; D006801:Humans; D056186:Metagenomics; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D010802:Phylogeny; D058974:Phylogeography; D014376:Tuberculosis / Q000453:epidemiology / Q000382:microbiology*