Daniel J. WilsonDerrick W. CrookTimothy E.A. PetoA. Sarah WalkerSarah J. HoosdallyAna L. Gibertoni CruzJoshua CarterClara GrazianSarah G. EarleSamaneh KouchakiAlexander LachapelleYang YangDavid A. CliftonPhilip W. FowlerZamin IqbalMartin HuntJeffrey KnaggsE. Grace SmithPriti RathodLisa JarrettDaniela MatiasDaniela M. CirilloEmanuele BorroniSimone BattagliaArash GhodousiAndrea SpitaleriAndrea CabibbeSabira TahseenKayzad NilgiriwalaSanchi ShahCamilla RodriguesPriti KambliUtkarsha SurveRukhsar KhotStefan NiemannThomas A. KohlMatthias MerkerHarald HoffmannKatharina TodtSara PlesnikNazir IsmailShaheed Vally OmarLavania JosephGuy ThwaitesThuong Nguyen Thuy ThuongNhung Hoang NgocVijay SrinivasanTimothy M. WalkerDavid MooreJorge CoronelWalter SolanoGeorge F. GaoGuangxue HeYanlin ZhaoChunfa LiuAijing MaBaoli ZhuIan LaurensonPauline ClaxtonAnastasia KochRobert WilkinsonAjit LalvaniJames PoseyJennifer GardyJim WerngrenNicholas PatonRuwen JouMei Hua WuWan Hsuan LinLucilaine FerrazoliRosangela Siqueira de OliveiraIrena ArandjelovicAngkana ChaiprasertInaki ComasFrancis A. DrobniewskiMaha R. FarhatQian GaoRick Ong Twee HeeVitali SintchenkoPhilip SupplyDick van SoolingenSiriraj HospitalPublic Health Agency of SwedenOxford University Clinical Research UnitSecond Affiliated Hospital of Southern University of Science and TechnologyPublic Health EnglandUniversité de LilleCentro de Investigación Biomédica en Red de Epidemiología y Salud PúblicaForschungszentrum Borstel - Zentrum für Medizin und BiowissenschaftenBelgrade University School of MedicineThe Foundation for Medical Research IndiaCSIC - Instituto de Biomedicina de Valencia (IBV)National Institute for Communicable DiseasesLondon School of Hygiene & Tropical MedicineInstituto Adolfo LutzUniversity of OxfordNational Institute for Public Health and the EnvironmentEuropean Bioinformatics InstituteThe University of SydneyIRCCS Ospedale San RaffaeleAsklepios Fachkliniken München-GautingP.D. Hinduja National Hospital and Medical Research CentreCenters for Disease Control and PreventionInstitute of Microbiology Chinese Academy of SciencesNational University of SingaporeImperial College LondonThe University of British ColumbiaFudan UniversityNuffield Department of MedicineHarvard Medical SchoolUniversity of Cape TownUniversidad Peruana Cayetano HeredaCDC TaiwanFISABIO-Public HealthNational Tuberculosis Control Program PakistanScottish Mycobacteria Reference LaboratoryChina CDC2022-08-042022-08-042021-01-01Molecular Biology and Evolution. Vol.37, No.8 (2021), 2450-246015371719073740382-s2.0-85089203677https://repository.li.mahidol.ac.th/handle/20.500.14594/75819The 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.Mahidol UniversityAgricultural and Biological SciencesBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1093/MOLBEV/MSAA069