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Positive selection underlies the species‐specific binding of Plasmodium falciparum RH 5 to human basigin
Author(s) -
Forni Diego,
Pontremoli Chiara,
Cagliani Rachele,
Pozzoli Uberto,
Clerici Mario,
Sironi Manuela
Publication year - 2015
Publication title -
molecular ecology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.619
H-Index - 225
eISSN - 1365-294X
pISSN - 0962-1083
DOI - 10.1111/mec.13354
Subject(s) - basigin , biology , plasmodium falciparum , genetics , lineage (genetic) , population , evolutionary biology , gene , malaria , immunology , demography , sociology , matrix metalloproteinase
Plasmodium falciparum , the causative agent of the deadliest form of malaria, is a member of the Laverania subgenus, which includes ape‐infecting parasites. P. falciparum is thought to have originated in gorillas, although infection is now restricted to humans. Laverania parasites display remarkable host‐specificity, which is partially mediated by the interaction between parasite ligands and host receptors. We analyse the evolution of BSG (basigin) and GYPA (glycophorin A) in primates/hominins, as well as of their Plasmodium ‐encoded ligands, Pf RH 5 and Pf EBA 175. We show that, in primates, positive selection targeted two sites in BSG (F27 and H102), both involved in Pf RH 5 binding. A population genetics–phylogenetics approach detected the strongest selection for the gorilla lineage: one of the positively selected sites (K191) is a major determinant of Pf RH 5 binding affinity. Analysis of RH 5 genes indicated episodic selection on the P. falciparum branch; the positively selected W447 site is known to stabilize the interaction with human basigin. Conversely, we detect no selection in the receptor‐binding region of EBA 175 in the P. falciparum lineage. Its host receptor, GYPA , shows evidence of positive selection in all hominid lineages; selected codons include glycosylation sites that modulate Pf EBA 175 binding affinity. Data herein provide an evolutionary explanation for species‐specific binding of the Pf RH 5‐ BSG ligand–receptor pair and support the hypothesis that positive selection at these genes drove the host shift leading to the emergence of P. falciparum as a human pathogen.

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