Extrachromosomal DNA amplicons in antimalarial-resistant Plasmodium falciparum

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dc.contributor.authorMcDaniels, Jennifer M.en
dc.contributor.authorHuckaby, Adam C.en
dc.contributor.authorCarter, Sabrina A.en
dc.contributor.authorLingeman, Sabrinaen
dc.contributor.authorFrancis, Audreyen
dc.contributor.authorCongdon, Mollyen
dc.contributor.authorSantos, Webster L.en
dc.contributor.authorRathod, Pradipsinh K.en
dc.contributor.authorGuler, Jennifer L.en
dc.contributor.departmentChemistryen
dc.date.accessioned2021-02-15T13:39:21Zen
dc.date.available2021-02-15T13:39:21Zen
dc.date.issued2020-10-14en
dc.description.abstractExtrachromosomal (ec) DNAs are genetic elements that exist separately from the genome. Since ecDNA can carry beneficial genes, they are a powerful adaptive mechanism in cancers and many pathogens. For the first time, we report ecDNA contributing to antimalarial resistance in Plasmodium falciparum, the most virulent human malaria parasite. Using pulse field gel electrophoresis combined with PCR-based copy number analysis, we detected two ecDNA elements that differ in migration and structure. Entrapment in the electrophoresis well and low susceptibility to exonucleases revealed that the biologically relevant ecDNA element is large and complex in structure. Using deep sequencing, we show that ecDNA originates from the chromosome and expansion of an ecDNA-specific sequence may improve its segregation or expression. We speculate that ecDNA is maintained using established mechanisms due to shared characteristics with the mitochondrial genome. Implications of ecDNA discovery in this organism are wide-reaching due to the potential for new strategies to target resistance development.en
dc.description.notesUniversity of Virginia, Grant/Award Number: Startupfunds; National Institutes of Health, Grant/Award Number: T32AI007046, AI089688 and AI093380en
dc.description.sponsorshipUniversity of Virginia; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [T32AI007046, AI089688, AI093380]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1111/mmi.14624en
dc.identifier.eissn1365-2958en
dc.identifier.issn0950-382Xen
dc.identifier.pmid33053232en
dc.identifier.urihttp://hdl.handle.net/10919/102367en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectadaptationen
dc.subjectextrachromosomal DNAen
dc.subjectgenomeen
dc.subjectmalariaen
dc.subjectPlasmodiumen
dc.subjectresistanceen
dc.titleExtrachromosomal DNA amplicons in antimalarial-resistant Plasmodium falciparumen
dc.title.serialMolecular Microbiologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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Destination Area: Global Systems Science (GSS)