{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T13:11:21Z","timestamp":1791983481073,"version":"4.4.0"},"reference-count":74,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T00:00:00Z","timestamp":1738627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01-AI149779"],"award-info":[{"award-number":["R01-AI149779"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    The\n                    <jats:italic>var<\/jats:italic>\n                    multigene family encodes\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    erythrocyte membrane protein 1 (PfEMP1), central to host-parasite interactions. Genome structure studies have identified three major groups of\n                    <jats:italic>var<\/jats:italic>\n                    genes by specific upstream sequences (upsA, B, or C).\n                    <jats:italic>Var<\/jats:italic>\n                    with these ups groups have different chromosomal locations, transcriptional directions, and associations with disease severity. Here we explore temporal and spatial diversity of a region of\n                    <jats:italic>var<\/jats:italic>\n                    genes encoding the DBL\u03b1 domain of PfEMP1 in Africa. By applying a novel ups classification algorithm (\n                    <jats:italic>cUps<\/jats:italic>\n                    ) to publicly-available DBL\u03b1 sequence datasets, we categorised DBL\u03b1 according to association with the three ups groups, thereby avoiding the need to sequence complete genes. Data from deep sequencing of DBL\u03b1 types in a local population in northern Ghana surveyed seven times from 2012 to 2017 found variants with rare-to-moderate-to-extreme frequencies, and the common variants were temporally stable in this local endemic area. Furthermore, we observed that every isolate repertoire, whether mono- or multiclonal, comprised DBL\u03b1 types occurring with these frequency ranges implying a common genome structure. When comparing African countries of Ghana, Gabon, Malawi, and Uganda, we report that some DBL\u03b1 types were consistently found at high frequencies in multiple African countries while others were common only at the country level. The implication of these local and pan-Africa population patterns is discussed in terms of advantage to the parasite with regards to within-host adaptation and resilience to malaria control.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1012813","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T13:33:13Z","timestamp":1738675993000},"page":"e1012813","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["A paradoxical population structure of var DBL\u03b1 types in Africa"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3396-8213","authenticated-orcid":true,"given":"Mun Hua","family":"Tan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3305-0533","authenticated-orcid":true,"given":"Kathryn E.","family":"Tiedje","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"Pascual","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heejung","family":"Shim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao-ban","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6115-6135","authenticated-orcid":true,"given":"Karen P.","family":"Day","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,2,4]]},"reference":[{"issue":"9","key":"ppat.1012813.ref001","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1128\/EC.00173-07","article-title":"Antigenic Variation in Plasmodium falciparum: Gene Organization and Regulation of the var Multigene Family","volume":"6","author":"SA Kyes","year":"2007","journal-title":"Eukaryot Cell"},{"issue":"6","key":"ppat.1012813.ref002","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/s41564-018-0162-2","article-title":"Genomes of all known members of a Plasmodium subgenus reveal paths to virulent human malaria","volume":"3","author":"TD Otto","year":"2018","journal-title":"Nat Microbiol"},{"issue":"3","key":"ppat.1012813.ref003","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/nm0398-358","article-title":"Parasite antigens on the infected red cell surface are targets for naturally acquired immunity to malaria","volume":"4","author":"PC Bull","year":"1998","journal-title":"Nat Med"},{"issue":"6906","key":"ppat.1012813.ref004","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/nature01097","article-title":"Genome sequence of the human malaria parasite Plasmodium falciparum","volume":"419","author":"MJ Gardner","year":"2002","journal-title":"Nature"},{"issue":"52","key":"ppat.1012813.ref005","article-title":"Long read assemblies of geographically dispersed Plasmodium falciparum isolates reveal highly structured subtelomeres [version 1; peer review: 3 approved].","volume":"3","author":"TD Otto","year":"2018","journal-title":"Wellcome Open Res"},{"issue":"3","key":"ppat.1012813.ref006","first-page":"439","volume":"13","author":"Q Chen","year":"2000","journal-title":"Molecular Aspects of Severe Malaria. 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