Local adaptation in populations of Mycobacterium tuberculosis endemic to the Indian Ocean Rim

This work was supported by the Swiss National Science Foundation (grants 310030_188888, CRSII5_177163, IZRJZ3_164171 and IZLSZ3_170834) and the European Research Council (309540‑EVODRTB and 883582-ECOEVODRTB)Swiss Tropical and Public Health Institute. Department of Medical Parasitology and Infection Biology. Basel, Switzerland / University of Basel. Basel, Switzerland.Swiss Tropical and Public Health Institute. Department of Medical Parasitology and Infection Biology. Basel, Switzerland / University of Basel. Basel, Switzerland.Swiss Tropical and Public Health Institute. Department of Medical Parasitology and Infection Biology. Basel, Switzerland / University of Basel. Basel, Switzerland.Swiss Tropical and Public Health Institute. Department of Medical Parasitology and Infection Biology. Basel, Switzerland / University of Basel. Basel, Switzerland.Institute of Biomedicine of Valencia. Valencia, Spain.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Laboratório de Micobactérias. Rio de Janeiro, RJ, Brazil / Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Programa de Pós-graduação em Pesquisa Clínica e Doenças Infecciosas. Rio de Janeiro, RJ, Brazil.University of Valencia- joint Unit. I2SysBio,Valencia, Spain.University of Cape Town. Wellcome Centre for Infectious Diseases Research in Africa. Institute of Infectious Diseases and Molecular Medicine. Cape Town, South Africa.Makerere University. Department of Medical Microbiology. Kampala, Uganda.National Health Research Institutes. National Institute of Infectious Diseases and Vaccinology. Zhunan, Taiwan.Swiss Tropical and Public Health Institute. Department of Medical Parasitology and Infection Biology. Basel, Switzerland / University of Basel. Basel, Switzerland.Swiss Tropical and Public Health Institute. Department of Medical Parasitology and Infection Biology. Basel, Switzerland / University of Basel. Basel, Switzerland / University of Bern. Institute for Social and Preventive Medicine. Switzerland.Victorian Infectious Diseases Reference Laboratory. Victoria, Australia.Fudan University. School of Basic Medical Science. Institutes of Biomedical Sciences and Institute of Medical Microbiology. The Key Laboratory of Medical Molecular Virology of Ministries of Education and Health. Shanghai, China.Instituto de Investigación Sanitaria Gregorio Marañón. Hospital General Universitario Gregorio Marañón. Madrid, Spain / CIBER Enfermedades Respiratorias. Spain.Universitat de Barcelona. Hospital Clínic. Barcelona Institute for Global Health. Barcelona, Spain / Centro de Investigação em Saúde de Manhiça. Maputo, Mozambique.Swiss Tropical and Public Health Institute. Department of Medical Parasitology and Infection Biology. Basel, Switzerland / University of Basel. Basel, Switzerland.Swiss Tropical and Public Health Institute. Department of Medical Parasitology and Infection Biology. Basel, Switzerland / University of Basel. Basel, Switzerland / United Republic of Tanzania. Ifakara Health Institute, Bagamoyo, Bagamoyo District Hospital. Bagamoyo, Tanzania.Swiss Tropical and Public Health Institute. Department of Medical Parasitology and Infection Biology. Basel, Switzerland / University of Basel. Basel, Switzerland.Swiss Tropical and Public Health Institute. Department of Medical Parasitology and Infection Biology. Basel, Switzerland / University of Basel. Basel, Switzerland.Swiss Tropical and Public Health Institute. Department of Medical Parasitology and Infection Biology. Basel, Switzerland / University of Basel. Basel, Switzerland / United Republic of Tanzania. Ifakara Health Institute. Bagamoyo District Hospital. Bagamoyo, Tanzania.University of California. School of Medicine. San Francisco, USA.Fudan University. School of Basic Medical Science. Institutes of Biomedical Sciences and Institute of Medical Microbiology. The Key Laboratory of Medical Molecular Virology of Ministries of Education and Health. Shanghai, China.Swiss Tropical and Public Health Institute. Department of Medical Parasitology and Infection Biology. Basel, Switzerland / University of Basel. Basel, Switzerland / Papua New Guinea Institute of Medical Research. Goroka, Papua New Guinea.Swiss Tropical and Public Health Institute. Department of Medical Parasitology and Infection Biology. Basel, Switzerland / University of Basel. Basel, Switzerland.Mahidol University. Faculty of Science. Department of Microbiology. Pornchai Matangkasombut Center for Microbial Genomics / National Science and Technology Development Agency. Bangkok, Thailand.Swiss Tropical and Public Health Institute. Department of Medical Parasitology and Infection Biology. Basel, Switzerland / University of Basel. Basel, Switzerland.Mahidol University. Faculty of Science. Department of Microbiology. Pornchai Matangkasombut Center for Microbial Genomics / National Science and Technology Development Agency. Bangkok, Thailand.Institut Pasteur de Madagascar. Mycobacteriology Unit. Antananarivo, Madagascar.Institut Pasteur de Madagascar. Mycobacteriology Unit. Antananarivo, Madagascar.Swiss Tropical and Public Health Institute. Department of Medical Parasitology and Infection Biology. Basel, Switzerland / University of Basel. Basel, Switzerland.University of Basel. Basel, Switzerland / Swiss Tropical and Public Health Institute. Department of Medicine. Basel, Switzerland.Swiss Tropical and Public Health Institute. Department of Medical Parasitology and Infection Biology. Basel, Switzerland / University of Basel. Basel, Switzerland / United Republic of Tanzania. Ifakara Health Institute. Bagamoyo District Hospital. Bagamoyo, Tanzania.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Laboratório de Micobactérias. Rio de Janeiro, RJ, Brazil.Université Paris-Saclay. Paris, France / Paris Diderot University. Sorbonne Paris Cité. Paris, France.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada a Micobactérias. Rio de Janeiro, RJ, Brazil.Universidade do Estado do Pará. Centro de Ciências Biológicas e da Saúde. Programa de Pós-graduação em Biologia Parasitária na Amazônia. Belém, PA, Brazil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.University of Ghana. Noguchi Memorial Institute for Medical Research. Accra, Ghana.ETH Zürich. Department of Biosystems Science and Engineering. Basel, Switzerland.Swiss Tropical and Public Health Institute. Department of Medical Parasitology and Infection Biology. Basel, Switzerland / University of Basel. Basel, Switzerland.Swiss Tropical and Public Health Institute. Department of Medical Parasitology and Infection Biology. Basel, Switzerland / University of Basel. Basel, Switzerland.Lineage 1 (L1) and 3 (L3) are two lineages of the Mycobacterium tuberculosis complex (MTBC), causing tuberculosis (TB) in humans. L1 and L3 are endemic to 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. Here we analyzed 2,938 L1 and 2,030 L3 whole genome sequences originating from 69 countries. We show that South Asia played a central role in the dispersion of these two lineages to neighboring regions. Moreover, we found that L1 exhibits 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. 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