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 analyzed the evolution of BSG (basigin) and GYPA (glycophorin A) in primates/hominins, as well as of their Plasmodium-encoded ligands, PfRH5 and PfEBA175. We show that BSG evolved adaptively in primates with selection targeting two sites (F27 and H102) involved in PfRH5 binding. A population-genetic phylogentics approach detected the strongest selection for the gorilla lineage: one of the positively selected sites (K191) is a major determinant of PfRH5 binding affinity. Analysis of RH5 genes indicated adaptive evolution on the P. falciparum branch; the positively selected W447 site is known to stabilize the interaction with human basigin. Conversely, we detect no selection at EBA175 gene 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 PfEBA175 binding affinity. Data herein provide an evolutionary explanation for species-specific binding of the PfRH5-BSG ligand-receptor pair and support the role of adaptive evolution at these genes as a determinant of the host shift that led to the emergence of P. falciparum as a human pathogen. A minor role in this process seems to have been played by the interaction between EBA175 and GYPA.
Positive selection underlies the species-specific binding of P. falciparum RH5 to human basigin / D. Forni, C. Pontremoli, R. Cagliani, U. Pozzoli, M. Clerici, M. Sironi. ((Intervento presentato al 6. convegno ISEB tenutosi a Bologna nel 2015.
|Titolo:||Positive selection underlies the species-specific binding of P. falciparum RH5 to human basigin|
FORNI, DIEGO (Corresponding)
PONTREMOLI, CHIARA (Corresponding)
CAGLIANI, RACHELE ANGELA (Corresponding)
CLERICI, MARIO SALVATORE (Corresponding)
|Data di pubblicazione:||31-ago-2015|
|Settore Scientifico Disciplinare:||Settore BIO/18 - Genetica|
|Citazione:||Positive selection underlies the species-specific binding of P. falciparum RH5 to human basigin / D. Forni, C. Pontremoli, R. Cagliani, U. Pozzoli, M. Clerici, M. Sironi. ((Intervento presentato al 6. convegno ISEB tenutosi a Bologna nel 2015.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|