Evolutionary history of human Plasmodium vivax revealed by genome-wide analyses of related ape parasites

Loy, D. E. et al. (2018) Evolutionary history of human Plasmodium vivax revealed by genome-wide analyses of related ape parasites. Proceedings of the National Academy of Sciences of the United States of America, 115(36), E8450-E8459. (doi: 10.1073/pnas.1810053115) (PMID:30127015) (PMCID:PMC6130405)

Abstract

<jats:p>Wild-living African apes are endemically infected with parasites that are closely related to human <jats:italic>Plasmodium vivax</jats:italic>, a leading cause of malaria outside Africa. This finding suggests that the origin of <jats:italic>P. vivax</jats:italic> was in Africa, even though the parasite is now rare in humans there. To elucidate the emergence of human <jats:italic>P. vivax</jats:italic> and its relationship to the ape parasites, we analyzed genome sequence data of <jats:italic>P. vivax</jats:italic> strains infecting six chimpanzees and one gorilla from Cameroon, Gabon, and Côte d’Ivoire. We found that ape and human parasites share nearly identical core genomes, differing by only 2% of coding sequences. However, compared with the ape parasites, human strains of <jats:italic>P. vivax</jats:italic> exhibit about 10-fold less diversity and have a relative excess of nonsynonymous nucleotide polymorphisms, with site-frequency spectra suggesting they are subject to greatly relaxed purifying selection. These data suggest that human <jats:italic>P. vivax</jats:italic> has undergone an extreme bottleneck, followed by rapid population expansion. Investigating potential host-specificity determinants, we found that ape <jats:italic>P. vivax</jats:italic> parasites encode intact orthologs of three reticulocyte-binding protein genes (<jats:italic>rbp2d</jats:italic>, <jats:italic>rbp2e</jats:italic>, and <jats:italic>rbp3</jats:italic>), which are pseudogenes in all human <jats:italic>P. vivax</jats:italic> strains. However, binding studies of recombinant RBP2e and RBP3 proteins to human, chimpanzee, and gorilla erythrocytes revealed no evidence of host-specific barriers to red blood cell invasion. These data suggest that, from an ancient stock of <jats:italic>P. vivax</jats:italic> parasites capable of infecting both humans and apes, a severely bottlenecked lineage emerged out of Africa and underwent rapid population growth as it spread globally.</jats:p>

• Item Type: Articles
• Additional Information: This work was supported in part by NIH Grants R01 AI097137, R01 AI091595, R37 AI050529, and P30 AI045008 (to B.H.H.); a grant from the Agence Nationale de Recherche (Programme Blanc, Sciences de la Vie, de la Santé et des Ecosystémes, ANR 11 BSV3 021 01, Projet PRIMAL) (to M.P.); and an Australian Research Council Future Fellowship and Howard Hughes Medical Institute–Wellcome Trust International Research Scholar Award 208693/Z/17/Z (to W.-H.T.). D.E.L. was supported by an NIH Training Grant T32 AI 007532; O.A.M. was supported by Biotechnology and Biological Sciences Research Council Grant BB/M010996/1 (EASTBIO); and A.L.K.M. was supported by Wellcome Trust PhD Programme Grant 108905/Z/15/Z.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: MacLean, Dr Oscar
• Authors: Loy, D. E., Plenderleith, L. J., Sundararaman, S. A., Liu, W., Gruszczyk, J., Chen, Y.-J., Trimboli, S., Learn, G. H., MacLean, O. A., Morgan, A. L.K., Li, Y., Avitto, A. N., Giles, J., Calvignac-Spencer, S., Sachse, A., Leendertz, F. H., Speede, S., Ayouba, A., Peeters, M., Rayner, J. C., Tham, W.-H., Sharp, P. M., and Hahn, B. H.
• 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: Proceedings of the National Academy of Sciences of the United States of America
• Publisher: National Academy of Sciences
• ISSN: 0027-8424
• ISSN (Online): 1091-6490
• Published Online: 20 August 2018
• Copyright Holders: Copyright © 2018 The Authors
• First Published: First published in Proceedings of the National Academy of Sciences of the United States of America 115(36): E8450-E8459
• Publisher Policy: Reproduced under a Creative Commons License