Roberto AmatoOlivo MiottoCharles J. WoodrowJacob Almagro-GarciaIpsita SinhaSusana CampinoDaniel MeadEleanor DruryMihir KekreMandy SandersAlfred Amambua-NgwaChanaki AmaratungaLucas Amenga-EtegoVoahangy AndrianaranjakaTobias ApinjohElizabeth AshleySarah AuburnGordon A. AwandareVito BarakaAlyssa BarryMaciej F. BoniSteffen BorrmannTeun BousemaOralee BranchPeter C. BullKesinee ChotivanichDavid J. ConwayAlister CraigNicholas P. DayAbdoulaye DjimdéChristiane DolecekArjen M. DondorpChris DrakeleyPatrick DuffyDiego F. EcheverryThomas G. EgwangRick M. FairhurstAbul FaizCaterina I. FanelloTran Tinh HienAbraham HodgsonMallika ImwongDeus IshengomaPharath LimChanthap LonJutta MarfurtKevin MarshMayfong MayxayPascal MichonVictor MobegiOlugbenga A. MokuoluJacqui MontgomeryIvo MuellerMyat Phone KyawPaul N. NewtonFrancois NostenRintis NoviyantiAlexis NzilaHarold OchollaAbraham OduroMarie OnyambokoJean Bosco OuedraogoAung Pyae P. PhyoChristopher PloweRic N. PriceSasithon PukrittayakameeMilijaona RandrianarivelojosiaPascal RingwaldLastenia RuizDavid SaundersAlex ShayoPeter SibaShannon Takala-HarrisonThuy Nhien N. ThanhVandana ThathyFederica VerraJason WendlerWellcome Trust Sanger InstituteWellcome Trust Centre for Human GeneticsMahidol UniversityNuffield Department of Clinical MedicineMedical Research Council Laboratories GambiaNational Institute of Allergy and Infectious DiseasesNavrongo Health Research CenterInstitut Pasteur de MadagascarUniversity of BueaMenzies School of Health ResearchUniversity of GhanaNational Institute for Medical Research TangaUniversiteit AntwerpenWalter and Eliza Hall Institute of Medical ResearchUniversity of MelbourneUniversity of OxfordKenya Medical Research InstituteUniversität TübingenLondon School of Hygiene & Tropical MedicineNYU School of MedicineLiverpool School of Tropical MedicineUniversity of BamakoOxford University Clinical Research UnitPurdue UniversityCentro Internacional de Entrenamiento e Investigaciones MedicasMed Biotech Laboratories UgandaMalaria Research Group and Dev Care FoundationNational Centre for Parasitology, Entomology and Malaria ControlArmed Forces Research Institute of Medical Sciences, ThailandLao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU)University of Health SciencesDivine Word UniversityUniversity of IlorinPennsylvania State UniversityMinistry of HealthShoklo Malaria Research UnitEijkman Institute for Molecular BiologyKing Fahd University of Petroleum and MineralsMalawi-Liverpool-Wellcome TrustUniversite de KinshasaInstitut de Recherche en Sciences de la SantéUniversity of Maryland School of MedicineOrganisation Mondiale de la SanteUniversidad Nacional de la Amazonia Peruana, IquitosUniversity of DodomaPapua New Guinea Institute of Medical Research2018-12-112019-03-142018-12-112019-03-142016-03-04eLife. Vol.5, No.MARCH2016 (2016)2050084X2-s2.0-84961932806https://repository.li.mahidol.ac.th/handle/20.500.14594/43071© 2016, eLife Sciences Publications Ltd. All rights reserved. The current epidemic of artemisinin resistant Plasmodium falciparum in Southeast Asia is the result of a soft selective sweep involving at least 20 independent kelch13 mutations. In a large global survey, we find that kelch13 mutations which cause resistance in Southeast Asia are present at low frequency in Africa. We show that African kelch13 mutations have originated locally, and that kelch13 shows a normal variation pattern relative to other genes in Africa, whereas in Southeast Asia there is a great excess of non-synonymous mutations, many of which cause radical amino-acid changes. Thus, kelch13 is not currently undergoing strong selection in Africa, despite a deep reservoir of variations that could potentially allow resistance to emerge rapidly. The practical implications are that public health surveillance for artemisinin resistance should not rely on kelch13 data alone, and interventions to prevent resistance must account for local evolutionary conditions, shown by genomic epidemiology to differ greatly between geographical regions.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyImmunology and MicrobiologyArticleSCOPUS10.7554/eLife.08714