1. Adaptation of Plasmodium falciparum to humans involved the loss of an ape-specific erythrocyte invasion ligand
- Author
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Manoj T. Duraisingh, Alison Kemp, Julian C. Rayner, Selasi Dankwa, William R. Proto, Paul M. Sharp, Gavin J. Wright, Zenon A. Zenonos, Steve Unwin, Weimin Liu, Sasha V. Siegel, Sarah Marsden, Beatrice H. Hahn, Proto, William R [0000-0003-2311-920X], Siegel, Sasha V [0000-0002-1458-4348], Dankwa, Selasi [0000-0002-1837-2924], Sharp, Paul M [0000-0001-9771-543X], Hahn, Beatrice H [0000-0002-9400-9887], Rayner, Julian C [0000-0002-9835-1014], Apollo - University of Cambridge Repository, Proto, William R. [0000-0003-2311-920X], Siegel, Sasha V. [0000-0002-1458-4348], Sharp, Paul M. [0000-0001-9771-543X], Hahn, Beatrice H. [0000-0002-9400-9887], and Rayner, Julian C. [0000-0002-9835-1014]
- Subjects
0301 basic medicine ,Erythrocytes ,Protozoan Proteins ,General Physics and Astronomy ,medicine.disease_cause ,13 ,law.invention ,0302 clinical medicine ,law ,Loss of Function Mutation ,631/326/417/1716 ,Malaria, Falciparum ,lcsh:Science ,Frameshift Mutation ,Cell Engineering ,Genetics ,Gene Editing ,Mutation ,Multidisciplinary ,biology ,article ,Ligand (biochemistry) ,3. Good health ,Parasite biology ,13/31 ,Parasite evolution ,Recombinant DNA ,Pan troglodytes ,Science ,Plasmodium falciparum ,13/106 ,General Biochemistry, Genetics and Molecular Biology ,Laverania ,Host Specificity ,Frameshift mutation ,38/91 ,82/80 ,Evolution, Molecular ,03 medical and health sciences ,parasitic diseases ,medicine ,692/699/255/1629 ,Animals ,Humans ,631/326/417/2548 ,Gene ,HEK 293 cells ,General Chemistry ,biology.organism_classification ,Malaria ,030104 developmental biology ,HEK293 Cells ,Sialic Acids ,lcsh:Q ,CRISPR-Cas Systems ,030217 neurology & neurosurgery - 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., Here, Proto et al. show that human infective Plasmodium falciparum isolates contain an inactivating mutation in the erythrocyte invasion associated gene PfEBA165, while homologues of ape-infective Laverania species are intact, and that expression of intact PfEBA165 is incompatible with parasite growth in human erythrocytes.
- Published
- 2019