Fig. 6.

PfEBA165 inactivation may have predisposed P. falciparum ancestor to invade human erythrocytes. Invasion ligands function in a partially redundant manner during erythrocyte recognition, and gene deletion studies suggest a defined hierarchy of interactions. If EBA165, which only recognises ape-specific sialic acids (Neu5Gc), was the dominant invasion ligand in the ancestor of P. falciparum, inactivation may have allowed PfEBA175, which is not Neu5Gc specific, to play a more dominant role in invasion (left hand arrow). This would have either predisposed parasites to more effectively invade human erythrocytes, which only expresss Neu5Ac, or increased growth after host-species transition had occurred, selecting for strains where PfEBA165 was inactivated. By contrast ancestral parasites with a dominant and intact PfEBA165 would still primarily rely on Neu5Gc sialic acids for invasion, and hence would invade human erythrocytes less efficiently, reducing the likelihood of species transition, or reducing growth rates once the transition had occurred