Fabrizio MenardoSebastien GagneuxLiliana K. RutaihwaMichaela ZwyerSonia BorrellIñaki ComasEmilyn Costa ConceiçãoMireia CoscollaHelen CoxMoses JolobaHorng Yunn DouJulia FeldmannLukas FennerJanet FyfeQian GaoDarío García de ViedmaAlberto L. Garcia-BasteiroSebastian M. GygliJerry HellaHellen HizaLevan JugheliLujeko KamwelaMidori Kato-MaedaQingyun LiuSerej D. LeyChloe LoiseauSurakameth MahasirimongkolBijaya MallaPrasit PalittapongarnpimNiaina RakotosamimananaVoahangy RasolofoMiriam ReinhardKlaus ReitherMohamed SasamaloRafael Silva DuarteChristophe SolaPhilip SuffysKarla Valeria Batista LimaDorothy Yeboah-ManuChristian BeiselDaniela BritesUniversité Paris CitéInstituto de Investigación Sanitaria Gregorio MarañónUniversite Paris-SaclayInstituto de Salud Global de BarcelonaCentro de Investigación Biomédica en Red de Enfermedades RespiratoriasInstitut Pasteur de MadagascarPapua New Guinea Institute of Medical ResearchMakerere UniversityIfakara Health InstituteCSIC - Instituto de Biomedicina de Valencia (IBV)UCSF School of MedicineFundacao Oswaldo CruzETH ZürichInstituto Nacional de Infectologia Evandro Chagas (INI)Universitat BaselSwiss Tropical and Public Health Institute (Swiss TPH)Universidade do Estado do ParaUniversity of BernUniversity of GhanaMahidol UniversityNational Health Research Institutes TaiwanFudan UniversityInstituto Evandro ChagasThailand National Science and Technology Development AgencyVictorian Infectious Diseases Reference LaboratoryUniversitat de ValènciaUniversity of Cape TownUniversidade Federal do Rio de JaneiroCentro de Investigação em Saúde de Manhiça2022-08-042022-08-042021-01-01F1000Research. Vol.10, (2021)1759796X204614022-s2.0-85101966101https://repository.li.mahidol.ac.th/handle/20.500.14594/76403Background: Lineage 1 (L1) and 3 (L3) are two lineages of the Mycobacterium tuberculosis complex (MTBC) causing tuberculosis (TB) in humans. L1 and L3 are prevalent around the rim of the Indian Ocean, the region that accounts for most of the world's new TB cases. Despite their relevance for this region, L1 and L3 remain understudied. Methods: We analyzed 2,938 L1 and 2,030 L3 whole genome sequences originating from 69 countries. We reconstructed the evolutionary history of these two lineages and identified genes under positive selection. Results: We found a strongly asymmetric pattern of migration from South Asia toward neighboring regions, highlighting the historical role of South Asia in the dispersion of L1 and L3. Moreover, we found that several genes were under positive selection, including genes involved in virulence and resistance to antibiotics For L1 we identified signatures of local adaptation at the esxH locus, a gene coding for a secreted effector that targets the human endosomal sorting complex, and is included in several vaccine candidates. Conclusions: Our study highlights the importance of genetic diversity in the MTBC, and sheds new light on two of the most important MTBC lineages affecting humans.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyImmunology and MicrobiologyPharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.12688/f1000research.28318.1