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Adaptation of Plasmodium falciparum to humans involved the loss of an ape-specific erythrocyte invasion ligand

Author

Listed:
  • William R. Proto

    (Wellcome Sanger Institute, Wellcome Genome Campus)

  • Sasha V. Siegel

    (Wellcome Sanger Institute, Wellcome Genome Campus)

  • Selasi Dankwa

    (Harvard T.H. Chan School of Public Health)

  • Weimin Liu

    (University of Pennsylvania
    University of Pennsylvania)

  • Alison Kemp

    (Wellcome Sanger Institute, Wellcome Genome Campus)

  • Sarah Marsden

    (Wellcome Sanger Institute, Wellcome Genome Campus)

  • Zenon A. Zenonos

    (Wellcome Sanger Institute, Wellcome Genome Campus)

  • Steve Unwin

    (Chester Zoo
    University of Birmingham)

  • Paul M. Sharp

    (Institute of Evolutionary Biology, University of Edinburgh)

  • Gavin J. Wright

    (Wellcome Sanger Institute, Wellcome Genome Campus)

  • Beatrice H. Hahn

    (University of Pennsylvania
    University of Pennsylvania)

  • Manoj T. Duraisingh

    (Harvard T.H. Chan School of Public Health)

  • Julian C. Rayner

    (Wellcome Sanger Institute, Wellcome Genome Campus
    Cambridge Institute for Medical Research, University of Cambridge)

Abstract

Plasmodium species are frequently host-specific, but little is currently known about the molecular factors restricting host switching. This is particularly relevant for P. falciparum, the only known human-infective species of the Laverania sub-genus, all other members of which infect African apes. Here we show that all tested P. falciparum isolates contain an inactivating mutation in an erythrocyte invasion associated gene, PfEBA165, the homologues of which are intact in all ape-infective Laverania species. Recombinant EBA165 proteins only bind ape, not human, erythrocytes, and this specificity is due to differences in erythrocyte surface sialic acids. Correction of PfEBA165 inactivating mutations by genome editing yields viable parasites, but is associated with down regulation of both PfEBA165 and an adjacent invasion ligand, which suggests that PfEBA165 expression is incompatible with parasite growth in human erythrocytes. Pseudogenization of PfEBA165 may represent a key step in the emergence and evolution of P. falciparum.

Suggested Citation

  • William R. Proto & Sasha V. Siegel & Selasi Dankwa & Weimin Liu & Alison Kemp & Sarah Marsden & Zenon A. Zenonos & Steve Unwin & Paul M. Sharp & Gavin J. Wright & Beatrice H. Hahn & Manoj T. Duraising, 2019. "Adaptation of Plasmodium falciparum to humans involved the loss of an ape-specific erythrocyte invasion ligand," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12294-3
    DOI: 10.1038/s41467-019-12294-3
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