Adaptive evolution of RH5 in ape Plasmodium species of the Laverania subgenus

Plenderleith, L. J., Liu, W., MacLean, O. A. , Li, Y., Loy, D. E., Sundararaman, S. A., Bibollet-Ruche, F., Learn, G. H., Hahn, B. H. and Sharp, P. M. (2018) Adaptive evolution of RH5 in ape Plasmodium species of the Laverania subgenus. mBio, 9(1), e02237-17. (doi: 10.1128/mbio.02237-17) (PMID:29362238) (PMCID:PMC5784257)

Abstract

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.

• Item Type: Articles
• Additional Information: This work was supported by grants from the National Institutes of Health (grants number R01 AI 091595, R01 AI 120810, R37 AI 050529, T32 AI 007532, and P30 AI 045008). This project was also supported by Biotechnology and Biological Sciences Research Council (BBSRC) grant number BB/M010996/1 (EASTBIO).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: MacLean, Dr Oscar
• Authors: Plenderleith, L. J., Liu, W., MacLean, O. A., Li, Y., Loy, D. E., Sundararaman, S. A., Bibollet-Ruche, F., Learn, G. H., Hahn, B. H., and Sharp, P. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: mBio
• Publisher: American Society for Microbiology
• ISSN: 2150-7511
• ISSN (Online): 2150-7511
• Published Online: 23 January 2018
• Copyright Holders: Copyright © 2018 Plenderleith et al.
• First Published: First published in mBio 9(1): e02237-17
• Publisher Policy: Reproduced under a Creative Commons License