{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T23:34:44Z","timestamp":1791934484696,"version":"4.3.4"},"reference-count":53,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2016,3,4]],"date-time":"2016-03-04T00:00:00Z","timestamp":1457049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"},{"start":{"date-parts":[[2016,3,4]],"date-time":"2016-03-04T00:00:00Z","timestamp":1457049600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"},{"start":{"date-parts":[[2016,3,4]],"date-time":"2016-03-04T00:00:00Z","timestamp":1457049600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT Sanger Institute Core Funding, 98051"],"award-info":[{"award-number":["WT Sanger Institute Core Funding, 98051"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT Centre for Human Genetics Core Funding, 090532\/Z\/09\/Z"],"award-info":[{"award-number":["WT Centre for Human Genetics Core Funding, 090532\/Z\/09\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT Stategic Award, 90770"],"award-info":[{"award-number":["WT Stategic Award, 90770"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["Centre for Genomics and Global Health, G0600718"],"award-info":[{"award-number":["Centre for Genomics and Global Health, G0600718"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["Grant OPP1040463"],"award-info":[{"award-number":["Grant OPP1040463"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT Mahidol University Oxford Tropical Medicine Research Programme, 0892375\/H\/09\/Z"],"award-info":[{"award-number":["WT Mahidol University Oxford Tropical Medicine Research Programme, 0892375\/H\/09\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["Intramural Research Program"],"award-info":[{"award-number":["Intramural Research Program"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.7554\/elife.08714","type":"journal-article","created":{"date-parts":[[2016,3,2]],"date-time":"2016-03-02T07:59:44Z","timestamp":1456905584000},"source":"Crossref","is-referenced-by-count":248,"title":["Genomic epidemiology of artemisinin resistant malaria"],"prefix":"10.7554","volume":"5","author":[{"name":"MalariaGEN Plasmodium falciparum Community Project","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2016,3,4]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/S0962-8924(99)01673-6","article-title":"The kelch repeat superfamily of proteins: propellers of cell function","volume":"10","author":"Adams","year":"2000","journal-title":"Trends in Cell Biology"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1038\/nature12876","article-title":"A molecular marker of artemisinin-resistant plasmodium falciparum malaria","volume":"505","author":"Ariey","year":"2014","journal-title":"Nature"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1056\/NEJMoa1314981","article-title":"Spread of artemisinin resistance in plasmodium falciparum malaria","volume":"371","author":"Ashley","year":"2014","journal-title":"New England Journal of Medicine"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"e22213","DOI":"10.1371\/journal.pone.0022213","article-title":"An effective method to purify plasmodium falciparum DNA directly from clinical blood samples for whole genome high-throughput sequencing","volume":"6","author":"Auburn","year":"2011","journal-title":"PLoS ONE"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1038\/nature07517","article-title":"Accurate whole human genome sequencing using reversible terminator chemistry","volume":"456","author":"Bentley","year":"2008","journal-title":"Nature"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1186\/1471-2105-9-236","article-title":"A novel series of compositionally biased substitution matrices for comparing plasmodium proteins","volume":"9","author":"Brick","year":"2008","journal-title":"BMC Bioinformatics"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"e1004812","DOI":"10.1371\/journal.pgen.1004812","article-title":"Generation of antigenic diversity in plasmodium falciparum by structured rearrangement of var genes during mitosis","volume":"10","author":"Claessens","year":"2014","journal-title":"PLoS Genetics"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"e1002132","DOI":"10.1371\/journal.pbio.1002132","article-title":"Targeting the cell stress response of plasmodium falciparum to overcome artemisinin resistance","volume":"13","author":"Dogovski","year":"2015","journal-title":"PLOS Biology"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1056\/NEJMoa0808859","article-title":"Artemisinin resistance in plasmodium falciparum malaria","volume":"361","author":"Dondorp","year":"2009","journal-title":"New England Journal of Medicine"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/j.pt.2013.05.005","article-title":"Artemisinin resistance is a clear and present danger","volume":"29","author":"Dondorp","year":"2013","journal-title":"Trends in Parasitology"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"5793","DOI":"10.1073\/pnas.92.13.5793","article-title":"Evolutionary origin of plasmodium and other apicomplexa based on rRNA genes","volume":"92","author":"Escalante","year":"1995","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1186\/1475-2875-10-339","article-title":"Standardizing the measurement of parasite clearance in falciparum malaria: the parasite clearance estimator","volume":"10","author":"Flegg","year":"2011","journal-title":"Malaria Journal"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1186\/1471-2148-11-257","article-title":"Protein-based signatures of functional evolution in plasmodium falciparum","volume":"11","author":"Gardner","year":"2011","journal-title":"BMC Evolutionary Biology"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"e1005004","DOI":"10.1371\/journal.pgen.1005004","article-title":"Recent selective sweeps in north american drosophila melanogaster show signatures of soft sweeps","volume":"11","author":"Garud","year":"2015","journal-title":"PLOS Genetics"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1038\/nbt.2925","article-title":"Genome editing in the human malaria parasite plasmodium falciparum using the CRISPR-Cas9 system","volume":"32","author":"Ghorbal","year":"2014","journal-title":"Nature Biotechnology"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1093\/biomet\/53.3-4.325","article-title":"Some distance properties of latent root and vector methods used in multivariate analysis","volume":"53","author":"Gower","year":"1966","journal-title":"Biometrika"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/S1471-4922(02)00017-X","article-title":"Malaria control and the evolution of drug resistance: an intriguing link","volume":"19","author":"Hastings","year":"2003","journal-title":"Trends in Parasitology"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"10915","DOI":"10.1073\/pnas.89.22.10915","article-title":"Amino acid substitution matrices from protein blocks","volume":"89","author":"Henikoff","year":"1992","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"2335","DOI":"10.1534\/genetics.104.036947","article-title":"Soft sweeps: molecular population genetics of adaptation from standing genetic variation","volume":"169","author":"Hermisson","year":"2005","journal-title":"Genetics"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1186\/1475-2875-11-355","article-title":"In vivo susceptibility of plasmodium falciparum to artesunate in binh phuoc province, vietnam","volume":"11","author":"Hien","year":"2012","journal-title":"Malaria Journal"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1093\/infdis\/jiu469","article-title":"Artemisinin resistance: the more we know, the more complicated it appears","volume":"211","author":"Hopkins Sibley","year":"2015","journal-title":"Journal of Infectious Diseases"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"5281","DOI":"10.1038\/ncomms6281","article-title":"On the unfounded enthusiasm for soft selective sweeps","volume":"5","author":"Jensen","year":"2014","journal-title":"Nature Communications"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1126\/science.1081449","article-title":"Early origin and recent expansion of plasmodium falciparum","volume":"300","author":"Joy","year":"2003","journal-title":"Science"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"1352","DOI":"10.1093\/infdis\/jiu608","article-title":"K13-propeller polymorphisms in plasmodium falciparum parasites from sub-saharan africa","volume":"211","author":"Kamau","year":"2015","journal-title":"The Journal of Infectious Diseases"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"e57689","DOI":"10.1371\/journal.pone.0057689","article-title":"Reduced susceptibility of plasmodium falciparum to artesunate in southern myanmar","volume":"8","author":"Kyaw","year":"2013","journal-title":"PLoS ONE"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/0022-2836(82)90515-0","article-title":"A simple method for displaying the hydropathic character of a protein","volume":"157","author":"Kyte","year":"1982","journal-title":"Journal of Molecular Biology"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"2947","DOI":"10.1093\/bioinformatics\/btm404","article-title":"Clustal w and clustal x version 2.0","volume":"23","author":"Larkin","year":"2007","journal-title":"Bioinformatics"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"e1002453","DOI":"10.1371\/journal.pgen.1002453","article-title":"Inference of population structure using dense haplotype data","volume":"8","author":"Lawson","year":"2012","journal-title":"PLoS Genetics"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with burrows-wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"2434","DOI":"10.1093\/bioinformatics\/btp403","article-title":"SNP-o-matic","volume":"25","author":"Manske","year":"2009","journal-title":"Bioinformatics"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1038\/nature11174","article-title":"Analysis of plasmodium falciparum diversity in natural infections by deep sequencing","volume":"487","author":"Manske","year":"2012","journal-title":"Nature"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1038\/nature14412","article-title":"A molecular mechanism of artemisinin resistance in plasmodium falciparum malaria","volume":"520","author":"Mbengue","year":"2015","journal-title":"Nature"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1016\/j.tree.2013.08.003","article-title":"Population genomics of rapid adaptation by soft selective sweeps","volume":"28","author":"Messer","year":"2013","journal-title":"Trends in Ecology & Evolution"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1038\/ng.2624","article-title":"Multiple populations of artemisinin-resistant plasmodium falciparum in cambodia","volume":"45","author":"Miotto","year":"2013","journal-title":"Nature Genetics"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1038\/ng.3189","article-title":"Genetic architecture of artemisinin-resistant plasmodium falciparum","volume":"47","author":"Miotto","year":"2015","journal-title":"Nature Genetics"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.parint.2009.04.004","article-title":"Spread and evolution of plasmodium falciparum drug resistance","volume":"58","author":"Mita","year":"2009","journal-title":"Parasitology International"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1126\/science.1260403","article-title":"Population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance","volume":"347","author":"Mok","year":"2015","journal-title":"Science"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"e335","DOI":"10.1371\/journal.pbio.0030335","article-title":"Recombination hotspots and population structure in plasmodium falciparum","volume":"3","author":"Mu","year":"2005","journal-title":"PLoS Biology"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1093\/molbev\/msl185","article-title":"Recurrent gene amplification and soft selective sweeps during evolution of multidrug resistance in malaria parasites","volume":"24","author":"Nair","year":"2007","journal-title":"Molecular Biology and Evolution"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1101\/gr.088336.108","article-title":"Darwinian and demographic forces affecting human protein coding genes","volume":"19","author":"Nielsen","year":"2009","journal-title":"Genome Research"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1093\/molbev\/msj117","article-title":"Soft sweeps II--molecular population genetics of adaptation from recurrent mutation or migration","volume":"23","author":"Pennings","year":"2006","journal-title":"Molecular Biology and Evolution"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"1960","DOI":"10.1016\/S0140-6736(12)60484-X","article-title":"Emergence of artemisinin-resistant malaria on the western border of thailand: a longitudinal study","volume":"379","author":"Phyo","year":"2012","journal-title":"The Lancet"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1038\/hdy.2009.127","article-title":"Effective size of the hierarchically structured populations of the agent of malaria: a coalescent-based model","volume":"104","author":"Prugnolle","year":"2010","journal-title":"Heredity"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1186\/1471-2334-10-163","article-title":"Tracing the origins and signatures of selection of antifolate resistance in island populations of plasmodium falciparum","volume":"10","author":"Salgueiro","year":"2010","journal-title":"BMC Infectious Diseases"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1056\/NEJMc1403007","article-title":"Dihydroartemisinin\u2013piperaquine failure in cambodia","volume":"371","author":"Saunders","year":"2014","journal-title":"New England Journal of Medicine"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1126\/science.1260867","article-title":"K13-propeller mutations confer artemisinin resistance in plasmodium falciparum clinical isolates","volume":"347","author":"Straimer","year":"2015","journal-title":"Science"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1093\/infdis\/jiu491","article-title":"Independent emergence of artemisinin resistance mutations among plasmodium falciparum in southeast asia","volume":"211","author":"Takala-Harrison","year":"2015","journal-title":"Journal of Infectious Diseases"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1016\/j.cub.2010.05.053","article-title":"Plasmodium falciparum accompanied the human expansion out of africa","volume":"20","author":"Tanabe","year":"2010","journal-title":"Current Biology"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1093\/infdis\/jiu467","article-title":"Absence of putative artemisinin resistance mutations among plasmodium falciparum in sub-saharan africa: a molecular epidemiologic study","volume":"211","author":"Taylor","year":"2015","journal-title":"Journal of Infectious Diseases"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/1475-2875-11-41","article-title":"Using CF11 cellulose columns to inexpensively and effectively remove human DNA from plasmodium falciparum-infected whole blood samples","volume":"11","author":"Venkatesan","year":"2012","journal-title":"Malaria Journal"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1016\/S1473-3099(13)70252-4","article-title":"Novel phenotypic assays for the detection of artemisinin-resistant plasmodium falciparum malaria in cambodia: in-vitro and ex-vivo drug-response studies","volume":"13","author":"Witkowski","year":"2013","journal-title":"The Lancet Infectious Diseases"},{"key":"bib52","volume-title":"Update on Artemisinin Resistance - September 2014","author":"World Health Organization","year":"2014"},{"key":"bib53","doi-asserted-by":"crossref","DOI":"10.30875\/9f925144-en","volume-title":"World Malaria Report 2014","author":"World Health Organization","year":"2014"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/08714\/elife-08714-v2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/08714\/elife-08714-v2.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/08714","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T20:45:31Z","timestamp":1697057131000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/08714"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,4]]},"references-count":53,"alternative-id":["10.7554\/eLife.08714"],"URL":"https:\/\/doi.org\/10.7554\/elife.08714","archive":["CLOCKSS"],"relation":{"is-supplemented-by":[{"id-type":"uri","id":"http:\/\/www.malariagen.net\/resource\/16","asserted-by":"subject"},{"id-type":"uri","id":"http:\/\/www.ebi.ac.uk\/ena\/data\/view\/ERP000190","asserted-by":"subject"},{"id-type":"uri","id":"http:\/\/www.ebi.ac.uk\/ena\/data\/view\/ERP000197","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.08714.030","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.726190107.793548610","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.08714.029","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.726190107.793524882","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,4]]},"article-number":"e08714"}}