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Diamonds in the rif

2025-04Artigo científico Acesso aberto
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dc.contributor.authorLawton, Jonathan G.
dc.contributor.authorZhou, Albert E.
dc.contributor.authorStucke, Emily M.
dc.contributor.authorTakala-Harrison, Shannon
dc.contributor.authorSilva, Joana C.
dc.contributor.authorTravassos, Mark A.
dc.contributor.institutionInstituto de Higiene e Medicina Tropical (IHMT)
dc.contributor.institutionVector borne diseases and pathogens (VBD)
dc.contributor.institutionGlobal Health and Tropical Medicine (GHTM)
dc.contributor.pblElsevier
dc.date.accessioned2025-09-29T21:57:43Z
dc.date.available2025-09-29T21:57:43Z
dc.date.issued2025-04
dc.descriptionFunding Information: This work was supported by National Institutes of Health grants R01HL130750 and R01HL146377 (NHLBI), U01AI112367 (NIAID), TL1TR003100 (NCATS), and F31AI178915 (NIAID). Publisher Copyright: © 2025 The Authors
dc.description.abstractThe repetitive interspersed family (rif) and subtelomeric variable open reading frames (stevor) are highly diverse multi-gene families in the malaria parasite Plasmodium falciparum. Embedded on the surface of infected erythrocytes, RIFIN and STEVOR proteins are involved in cytoadherence and immune evasion, but the extent of family-wide sequence diversity across strains has yet to be comprehensively investigated in light of improved resolution of the subtelomeric genome sequences. Using a k-mer frequency approach, we analyzed long-read genomic sequence data from 18 geographically diverse P. falciparum genome assemblies, including lab strains and clinical isolates. We hypothesized that k-mer sequence comparison can identify existing RIFIN and STEVOR subgroups, identify novel subgroups, and generate more robust and reliable estimates of family-wide sequence diversity. Full-length RIFIN and STEVOR proteins shared on average 49.5% and 61.1% amino acid k-mer similarity, respectively, which fell to 25.1% and 20% in the hypervariable regions alone. Despite this diversity, we identified 11 RIFINs and five STEVORs that were conserved across strains above expected thresholds. A subset of these strain-transcendent genes was similar and syntenic to genes in related Plasmodium species, suggesting an ancient origin. Additionally, in silico structural predictions from AlphaFold showed that three-dimensional structures of RIFIN receptor-binding regions were more conserved than their sequences suggested. Evolutionarily constrained RIFINs and STEVORs may have critical functions in parasite survival or pathogenesis. This study provides a framework for investigating diversity in highly variable multi-gene families and highlights the potential of strain-transcendent RIFIN and STEVOR proteins as vaccine candidates.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent11043080
dc.identifier.doi10.1016/j.meegid.2025.105725
dc.identifier.issn1567-1348
dc.identifier.otherPURE: 123206667
dc.identifier.otherPURE UUID: d3485a55-1ab2-4f48-b9aa-d3b5b7d0f2f4
dc.identifier.otherScopus: 85217438548
dc.identifier.otherWOS: 001427639900001
dc.identifier.otherPubMed: 39920908
dc.identifier.otherPubMedCentral: PMC12032969
dc.identifier.urihttp://hdl.handle.net/10362/188763
dc.identifier.urlhttps://www.scopus.com/pages/publications/85217438548
dc.language.isoeng
dc.peerreviewedyes
dc.subjectComparative genomics
dc.subjectMalaria
dc.subjectPlasmodium falciparum
dc.subjectRIFIN
dc.subjectSTEVOR
dc.subjectVariant surface antigens
dc.subjectMicrobiology
dc.subjectEcology, Evolution, Behavior and Systematics
dc.subjectMolecular Biology
dc.subjectGenetics
dc.subjectMicrobiology (medical)
dc.subjectInfectious Diseases
dc.subjectSDG 3 - Good Health and Well-being
dc.titleDiamonds in the rifen
dc.title.subtitleAlignment-free comparative genomics analysis reveals strain-transcendent Plasmodium falciparum antigens amidst extensive genetic diversityen
dc.typejournal article
degois.publication.titleInfection, Genetics and Evolution
degois.publication.volume129
dspace.entity.typePublication
rcaap.rightsopenAccess

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