Abstract
Understanding evolution of human pathogens requires looking beyond the effects of recent interventions. To study malaria parasites prior to widespread drug selection, Plasmodium falciparum genomes were sequenced from the oldest population-based set of archived research samples yet identified, placental blood collected in the Gambia between 1966 and 1971. High-quality data were obtained from 54 infected samples, showing that genomic complexity within infections was high, most infections were genetically unrelated, and no drug resistance alleles were detected. Strong signatures of positive selection are clearly seen at multiple loci throughout the genome, most of which encode surface proteins that bind erythrocytes and are targets of acquired antibody responses. Comparison of population samples obtained over a following period of almost 50 years revealed major directional allele frequency changes at several loci apart from drug resistance genes. Exceptional changes over this time are seen at gdv1 that regulates the rate of parasite sexual conversion required for transmission, and at the unlinked Pfsa1 and Pfsa3 loci previously associated with infection of individuals with sickle-cell trait. Other affected loci encode surface and transporter proteins warranting targeted functional analyses. This identification of key long-term adaptations is important for understanding and managing future evolution of malaria parasites.
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Data availability
All original data reported here are fully available as outlined in the tables and data spreadsheets in the Supplementary Data 1–9. This includes the parasite genome sequences from each of the individual samples, for which the European Nucleotide Archive (ENA) accession numbers are listed in Supplementary Data 1 and 6.
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Acknowledgements
We are grateful to current and previous members of staff at the MRC Unit in The Gambia and the London School of Hygiene and Tropical Medicine who, at different times enabled the maintenance of research sample archives. We thank Lindsay Stewart for support with DNA extraction processing, as well as Eleanor Drury, Victoria Simpson and Sonia Goncalves at the Wellcome Sanger Institute for support with processing of samples for sequencing. This research was supported by a European and Developing Countries Clinical Trials Partnership (EDCTP) Senior Fellowship Plus award (TMA2019SFP-2843-EGSAT) and a Wellcome Sanger Institute Senior International Fellowship award (S4739-IF-A.A.-N.) to A.A.-N., and an MRC Project Grant (MR/S009760/1) to D.J.C.
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A.A.-N.: Conceptualization, Resources, Methodology, Data curation, Investigation, Formal analysis, Validation, Funding acquisition, Writing – original draft, Writing – review and editing. M.F.D.: Investigation. C.J.D.: Resources, Writing – review and editing. U.d’A.: Resources, Writing – review and editing. D.P.K.: Methodology, Resources. D.J.C.: Conceptualization, Resources, Methodology, Data curation, Investigation, Formal analysis, Validation, Funding acquisition, Writing – original draft, Writing – review and editing.
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Amambua-Ngwa, A., Diop, M.F., Drakeley, C.J. et al. Major features of parasite adaptation revealed by genomes of Plasmodium falciparum population samples archived for over 50 years. Commun Biol (2026). https://doi.org/10.1038/s42003-025-09460-3
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DOI: https://doi.org/10.1038/s42003-025-09460-3
