1. GenomegaMap: within-species genome-widedN/dSestimation from over 10,000 genomes
- Author
-
Wilson, DJ, Crook, DW, Peto, TEA, Walker, AS, Hoosdally, SJ, Gibertoni Cruz, AL, Carter, J, Grazian, C, Earle, SG, Kouchaki, S, Lachapelle, A, Yang, Y, Clifton, DA, Fowler, PW, Iqbal, Z, Hunt, M, Knaggs, J, Smith, EG, Rathod, P, Jarrett, L, Matias, D, Cirillo, DM, Borroni, E, Battaglia, S, Ghodousi, A, Spitaleri, A, Cabibbe, A, Tahseen, S, Nilgiriwala, K, Shah, S, Rodrigues, C, Kambli, P, Surve, U, Khot, R, Niemann, S, Kohl, TA, Merker, M, Hoffmann, H, Todt, K, Plesnik, S, Ismail, N, Omar, SV, Joseph, L, Thwaites, G, Thuong, TNT, Ngoc, NH, Srinivasan, V, Walker, TM, Moore, D, Coronel, J, Solano, W, Gao, GF, He, G, Zhao, Y, Liu, C, Ma, A, Zhu, B, Laurenson, I, Claxton, P, Koch, A, Wilkinson, R, Lalvani, A, Posey, J, Gardy, J, Werngren, J, Paton, N, Jou, R, Wu, M-H, Lin, W-H, Ferrazoli, L, De Oliveira, RS, Arandjelovic, I, Chaiprasert, A, Comas, I, Roig, CJ, Drobniewski, FA, Farhat, MR, Gao, Q, Hee, ROT, Sintchenko, V, Supply, P, Van Soolingen, D, University of Oxford, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), D.J.W. is a Sir Henry Dale Fellow, jointly funded by the Wellcome Trust and the Royal Society (grant no. 101237/Z/13/B) and is a Big Data Institute Robertson Fellow. The CRyPTIC Consortium was supported by grants from the Bill and Melinda Gates Foundation (OPP1133541) and a Wellcome Trust/Newton Fund-MRC Collaborative Award (200205/Z/15/Z). F.A.D. was supported by the Imperial Biomedical Research Centre., Members of the CRyPTIC Consortium : Derrick W. Crook, Timothy E.A. Peto, A. Sarah Walker, Sarah J. Hoosdally, Ana L. Gibertoni Cruz, Joshua Carter, Clara Grazian, Sarah G. Earle, Samaneh Kouchaki, Alexander Lachapelle, Yang Yang, David A. Clifton, and Philip W. Fowler, University of Oxford, Zamin Iqbal, Martin Hunt, and Jeffrey Knaggs, European Bioinformatics Institute, E. Grace Smith, Priti Rathod, Lisa Jarrett, and Daniela Matias, Public Health England, Birmingham, Daniela M. Cirillo, Emanuele Borroni, Simone Battaglia, Arash Ghodousi, Andrea Spitaleri, and Andrea Cabibbe, Emerging Bacterial Pathogens Unit, IRCCS San Raffaele Scientific Institute, Milan, Sabira Tahseen, National Tuberculosis Control Program Pakistan, Islamabad, Kayzad Nilgiriwala and Sanchi Shah, The Foundation for Medical Research, Mumbai, Camilla Rodrigues, Priti Kambli, Utkarsha Surve, and Rukhsar Khot, P.D. Hinduja National Hospital and Medical Research Centre, Mumbai, Stefan Niemann, Thomas A. Kohl, and Matthias Merker, Research Center Borstel, Harald Hoffmann, Katharina Todt, and Sara Plesnik, Institute of Microbiology & Laboratory Medicine, IML Red, Gauting, Nazir Ismail, Shaheed Vally Omar, and Lavania Joseph, National Institute for Communicable Diseases, Johannesburg, Guy Thwaites, Thuong Nguyen Thuy Thuong, Nhung Hoang Ngoc, Vijay Srinivasan, and Timothy M. Walker, Oxford University Clinical Research Unit, Ho Chi Minh City, David Moore, Jorge Coronel and Walter Solano, London School of Hygiene and Tropical Medicine and Universidad Peruana Cayetano Heredá, Lima, George F. Gao, Guangxue He, Yanlin Zhao, and Chunfa Liu, China CDC, Beijing, Aijing Ma, Shenzhen Third People’s Hospital, Shenzhen, Baoli Zhu, Institute of Microbiology, CAS, Beijing, Ian Laurenson and Pauline Claxton, Scottish Mycobacteria Reference Laboratory, Edinburgh, Anastasia Koch, Robert Wilkinson, University of Cape Town, Ajit Lalvani, Imperial College London, James Posey, CDC Atlanta, Jennifer Gardy, University of British Columbia, Jim Werngren, Public Health Agency of Sweden, Nicholas Paton, National University of Singapore, Ruwen Jou, Mei-Hua Wu, Wan-Hsuan Lin, CDC Taiwan, Lucilaine Ferrazoli, Rosangela Siqueira de Oliveira, Institute Adolfo Lutz, São Paulo. Authors contributing to the CRyPTIC Consortium are (in alphabetical order): Irena Arandjelovic (Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia), Angkana Chaiprasert (Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand), Iñaki Comas (Instituto de Biomedicina de Valencia [IBV-CSIC], Calle Jaime Roig, Valencia, Spain, FISABIO Public Health, Valencia, Spain, CIBER in Epidemiology and Public Health, Madrid, Spain), Francis A. Drobniewski (Imperial College, London, UK), Maha R. Farhat (Harvard Medical School, Boston, USA), Qian Gao (Shanghai Medical College, Fudan University, Shanghai, China), Rick Ong Twee Hee (Saw Swee Hock School of Public Health, National University of Singapore, Singapore), Vitali Sintchenko (Centre for Infectious Diseases and Microbiology—Public Health, University of Sydney, Sydney, Australia), Philip Supply (Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019—UMR 8204—CIIL—Centre d’Infection et d’Immunité de Lille, F-59000 Lille, France), and Dick van Soolingen (National Institute for Public Health and the Environment [RIVM], Bilthoven, The Netherlands)., Supply, Philip, Consortium, CRyPTIC, University of Oxford [Oxford], Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Royal Society (UK), Bill & Melinda Gates Foundation, Newton Fund, Comas, Iñaki [0000-0001-5504-9408], and Comas, Iñaki
- Subjects
Natural selection ,[SDV]Life Sciences [q-bio] ,Population genetics ,adaptation ,Computational biology ,Biology ,AcademicSubjects/SCI01180 ,0601 Biochemistry and Cell Biology ,Genome ,Coalescent theory ,DEAD-box RNA Helicases ,Big data ,03 medical and health sciences ,0603 Evolutionary Biology ,big data ,Parent-dependent mutation ,Genetics ,dN/dS ,Adaptation ,Selection, Genetic ,Molecular Biology ,Allele frequency ,Ecology, Evolution, Behavior and Systematics ,Silent Mutation ,Selection (genetic algorithm) ,030304 developmental biology ,Evolutionary Biology ,0604 Genetics ,0303 health sciences ,Models, Genetic ,Phylogenetic tree ,030306 microbiology ,AcademicSubjects/SCI01130 ,natural selection ,Mycobacterium tuberculosis ,Recombination ,Resources ,recombination ,3. Good health ,[SDV] Life Sciences [q-bio] ,Genetic Techniques ,Mutation (genetic algorithm) ,parent-dependent mutation ,Genome, Bacterial - Abstract
11 págs, 4 figuras y fórmulas matemáticas. Material suplementario en: http://dx.doi.org/10.1093/molbev/msaa069, The dN/dS ratio provides evidence of adaptation or functional constraint in protein-coding genes by quantifying the relative excess or deficit of amino acid-replacing versus silent nucleotide variation. Inexpensive sequencing promises a better understanding of parameters, such as dN/dS, but analyzing very large data sets poses a major statistical challenge. Here, I introduce genomegaMap for estimating within-species genome-wide variation in dN/dS, and I apply it to 3,979 genes across 10,209 tuberculosis genomes to characterize the selection pressures shaping this global pathogen. GenomegaMap is a phylogeny-free method that addresses two major problems with existing approaches: 1) It is fast no matter how large the sample size and 2) it is robust to recombination, which causes phylogenetic methods to report artefactual signals of adaptation. GenomegaMap uses population genetics theory to approximate the distribution of allele frequencies under general, parent-dependent mutation models. Coalescent simulations show that substitution parameters are well estimated even when genomegaMap's simplifying assumption of independence among sites is violated. I demonstrate the ability of genomegaMap to detect genuine signatures of selection at antimicrobial resistance-conferring substitutions in Mycobacterium tuberculosis and describe a novel signature of selection in the cold-shock DEAD-box protein A gene deaD/csdA. The genomegaMap approach helps accelerate the exploitation of big data for gaining new insights into evolution within species., D.J.W. is a Sir Henry Dale Fellow, jointly funded by the Wellcome Trust and the Royal Society (grant no. 101237/Z/13/B) and is a Big Data Institute Robertson Fellow. The CRyPTIC Consortium was supported by grants from the Bill and Melinda Gates Foundation (OPP1133541) and a Wellcome Trust/Newton Fund-MRC Collaborative Award (200205/Z/15/Z). F.A.D. was supported by the Imperial Biomedical Research Centre
- Published
- 2019