A paradoxical population structure of var DBLα types in Africa

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dc.contributor.authorTan, Mun Hua;
dc.contributor.authorTiedje, Kathryn E.;
dc.contributor.authorFeng, Qian ;
dc.contributor.authorZhan, Qi;
dc.contributor.authorPascual, Mercedes;
dc.contributor.authorShim, Heejung;
dc.contributor.authorChan, Yao-ban;
dc.contributor.authorDay, Karen P.
dc.date.accessioned2025-02-10T12:19:38Z
dc.date.available2025-02-10T12:19:38Z
dc.date.issued2025-02-04
dc.description.abstractThe var multigene family encodes Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), central to host-parasite interactions. Genome structure studies have identified three major groups of var genes by specific upstream sequences (upsA, B, or C). Var 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 var genes encoding the DBLα domain of PfEMP1 in Africa. By applying a novel ups classification algorithm ( cUps ) to publicly-available DBLα sequence datasets, we categorised DBLα according to association with the three ups groups, thereby avoiding the need to sequence complete genes. Data from deep sequencing of DBLα 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 DBLα 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 DBLα 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.
dc.description.sponsorshipThis study was funded by Fogarty International Center at the National Institutes of Health through the joint NIH-NSF-NIFA Ecology and Evolution of Infectious Diseases award R01-TW009670 to KPD and MP; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health through the joint NIH-NSF-NIFA Ecology and Evolution of Infectious Diseases award R01-AI149779 to KPD and MP. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Salary support for MT was provided by R01-AI149779 and for KET from R01-TW009670 and R01-AI149779.
dc.identifier.citationTan MH, Tiedje KE, Feng Q, Zhan Q, Pascual M, Shim H, et al. (2025) A paradoxical population structure of var DBLα types in Africa. PLoS Pathog 21(2): e1012813. https://doi.org/10.1371/journal.ppat.1012813
dc.identifier.issnISSN 1553-7374, 1553-7366
dc.identifier.issnEISSN 1553-7374
dc.identifier.urihttps://nru.uncst.go.ug/handle/123456789/9956
dc.language.isoen
dc.publisherPublic Library of Science
dc.titleA paradoxical population structure of var DBLα types in Africa
dc.typeArticle
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