Adaptive Evolution of RH5 in Ape Plasmodium species of the Laverania Subgenus

Lindsey J. Plenderleith, Weimin Liu, Oscar A. Maclean, Yingying Li, Dorothy E. Loy, Sesh A. Sundararaman, Frederic Bibollet-Ruche, Gerald H Learn, Beatrice H Hahn, Paul M. Sharp

Research output: Contribution to journalArticlepeer-review


Plasmodium falciparum, the major cause of malaria morbidity and mortality in humans, has been shown to have emerged after cross-species transmission of one of six host-specific parasites (subgenus Laverania) infecting wild chimpanzees (Pan troglodytes) and western gorillas (Gorilla gorilla). Binding of the parasite-encoded ligand RH5 to the host protein basigin is essential for erythrocyte invasion and has been implicated in host specificity. A recent study claimed to have found two amino acid changes in RH5 that “drove the host shift leading to the emergence of P. falciparum as a human pathogen.” However, the ape Laverania data available at that time, which included only a single distantly related chimpanzee parasite sequence, were inadequate to justify any such conclusion. Here, we have investigated Laverania Rh5 gene evolution using sequences from all six ape parasite species. Searching for gene-wide episodic selection across the entire Laverania phylogeny, we found eight codons to be under positive selection, including three that correspond to contact residues known to form hydrogen bonds between P. falciparum RH5 and human basigin. One of these sites (residue 197) has changed subsequent to the transmission from apes to humans that gave rise to P. falciparum, suggesting a possible role in the adaptation of the gorilla parasite to the human host. We also found evidence that the patterns of nucleotide polymorphisms in P. falciparum are not typical of Laverania species and likely reflect the recent demographic history of the human parasite.

Original languageEnglish
Article numbere02237-17
Number of pages11
Issue number1
Publication statusPublished - 23 Jan 2018


  • Laverania
  • Plasmodium falciparum
  • RH5
  • basigin
  • chimpanzee
  • gorilla


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