title: Turkish and Japanese Mycobacterium tuberculosis sublineages share a remote common ancestor.
abstract: Two geographically distant M. tuberculosis sublineages, Tur from Turkey and T3-Osaka from Japan, exhibit partially identical genotypic signatures (identical 12-loci MIRU-VNTR profiles, distinct spoligotyping patterns). We investigated T3-Osaka and Tur sublineages characteristics and potential genetic relatedness, first using MIRU-VNTR locus analysis on 21 and 25 samples of each sublineage respectively, and second comparing Whole Genome Sequences of 8 new samples to public data from 45 samples uncovering human tuberculosis diversity. We then tried to date their Most Recent Common Ancestor (MRCA) using three calibrations of SNP accumulation rate (long-term=0.03SNP/genome/year, derived from a tuberculosis ancestor of around 70,000years old; intermediate=0.2SNP/genome/year derived from a Peruvian mummy; short-term=0.5SNP/genome/year). To disentangle between these scenarios, we confronted the corresponding divergence times with major human history events and knowledge on human genetic divergence. We identified relatively high intrasublineage diversity for both T3-Osaka and Tur. We definitively proved their monophyly; the corresponding super-sublineage (referred to as "T3-Osa-Tur") shares a common ancestor with T3-Ethiopia and Ural sublineages but is only remotely related to other Euro-American sublineages such as X, LAM, Haarlem and S. The evolutionary scenario based on long-term evolution rate being valid until T3-Osa-Tur MRCA was not supported by Japanese fossil data. The evolutionary scenario relying on short-term evolution rate since T3-Osa-Tur MRCA was contradicted by human history and potential traces of past epidemics. T3-Osaka and Tur sublineages were found likely to have diverged between 800y and 2000years ago, potentially at the time of Mongol Empire. Altogether, this study definitively proves a strong genetic link between Turkish and Japanese tuberculosis. It provides a first hypothesis for calibrating TB Euro-American lineage molecular clock; additional studies are needed to reliably date events corresponding to intermediate depths in tuberculosis phylogeny.
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ Paris-Sud, Université Paris-Saclay, 91198, Gif-sur-Yvette cedex, France. Electronic address: guislaine.refregier@u-psud.fr.
authors.forename: Guislaine
authors.initials: G
authors.lastname: Refrégier
authors.affiliation: Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas, Venezuela.
authors.forename: Edgar
authors.initials: E
authors.lastname: Abadia
authors.affiliation: Department of Clinical Research and Development, Osaka Prefectural Hospital Organization, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Habikino-city, Japan.
authors.forename: Tomoshige
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Department of Clinical Research and Development, Osaka Prefectural Hospital Organization, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Habikino-city, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ano
authors.affiliation: Department of Clinical Research and Development, Osaka Prefectural Hospital Organization, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Habikino-city, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Takashima
authors.affiliation: Department of Clinical Research and Development, Osaka Prefectural Hospital Organization, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Habikino-city, Japan.
authors.forename: Izuo
authors.initials: I
authors.lastname: Tsuyuguchi
authors.affiliation: Şişli Etfal Research and Training Hopital, Istanbul, Turkey.
authors.forename: Elif
authors.initials: E
authors.lastname: Aktas
authors.affiliation: Faculty of Medicine, Bülent Ecevit University, Zonguldak, Turkey.
authors.forename: Füsun
authors.initials: F
authors.lastname: Cömert
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ Paris-Sud, Université Paris-Saclay, 91198, Gif-sur-Yvette cedex, France.
authors.forename: Michel Kireopori
authors.initials: MK
authors.lastname: Gomgnimbou
authors.affiliation: National Center of Parasitic and Infectious Diseases, Sofia, Bulgaria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Panaiotov
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK.
authors.forename: Jody
authors.initials: J
authors.lastname: Phelan
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK.
authors.forename: Francesc
authors.initials: F
authors.lastname: Coll
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK; Infection and Immunity Unit, UCT Lung Institute, University of Cape Town, Old Main Building, Groote Schuur Hospital, Cape Town,South Africa.
authors.forename: Ruth
authors.initials: R
authors.lastname: McNerney
authors.affiliation: Pathogen Genomics Group, Biological, Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia.
authors.forename: Arnab
authors.initials: A
authors.lastname: Pain
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK.
authors.forename: Taane G
authors.initials: TG
authors.lastname: Clark
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ Paris-Sud, Université Paris-Saclay, 91198, Gif-sur-Yvette cedex, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Sola
mesh_terms: D004269:DNA, Bacterial / Q000032:analysis / Q000235:genetics; D058872:Epidemics / Q000266:history / Q000706:statistics & numerical data; D019143:Evolution, Molecular; D005838:Genotype; D049669:History, 16th Century; D049670:History, 17th Century; D049671:History, 18th Century; D049690:History, Ancient; D049691:History, Medieval; D006801:Humans; D007564:Japan; D018598:Minisatellite Repeats / Q000235:genetics; D017720:Molecular Epidemiology; D058889:Molecular Typing; D009169:Mycobacterium tuberculosis / Q000145:classification* / Q000235:genetics*; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014376:Tuberculosis / Q000453:epidemiology* / Q000266:history / Q000382:microbiology*; D014421:Turkey
chemical_list: D004269:DNA, Bacterial
keywords: Molecular clock; Pathogen evolution; Phylogenetics; Phylogeography