Proto, William R, Siegel, Sasha V, Dankwa, Selasi et al. (10 more authors) (2019) Adaptation of Plasmodium falciparum to humans involved the loss of an ape-specific erythrocyte invasion ligand. Nature Communications. 4512. ISSN 2041-1723
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2019 |
Keywords: | first & last 3 (QQ only),first & last (all papers),parasites and microbes,staffpaper |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) The University of York > Faculty of Sciences (York) > Hull York Medical School (York) |
Depositing User: | Pure (York) |
Date Deposited: | 20 Oct 2020 15:10 |
Last Modified: | 02 Dec 2024 01:13 |
Published Version: | https://doi.org/10.1038/s41467-019-12294-3 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1038/s41467-019-12294-3 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:166964 |