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

Dorothy E. Loy, Lindsey J. Plenderleith, Sesh A. Sundararaman, Weimin Liu, Jakub Gruszczyk, Yi Jun Chen, Stephanie Trimboli, Gerald H. Learn, Oscar A. MacLean, Alex L.K. Morgan, Yingying Li, Alexa N. Avitto, Jasmin Giles, Sébastien Calvignac-Spencer, Andreas Sachse, Fabian H. Leendertz, Sheri Speede, Ahidjo Ayouba, Martine Peeters, Julian C. RaynerWai Hong Tham, Paul M. Sharp, Beatrice H. Hahn*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Wild-living African apes are endemically infected with parasites that are closely related to human Plasmodium vivax, a leading cause of malaria outside Africa. This finding suggests that the origin of P. vivax was in Africa, even though the parasite is now rare in humans there. To elucidate the emergence of human P. vivax and its relationship to the ape parasites, we analyzed genome sequence data of P. vivax 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 P. vivax 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 P. vivax has undergone an extreme bottleneck, followed by rapid population expansion. Investigating potential host-specificity determinants, we found that ape P. vivax parasites encode intact orthologs of three reticulocyte-binding protein genes (rbp2d, rbp2e, and rbp3), which are pseudogenes in all human P. vivax 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 P. vivax 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.

Original languageEnglish
Pages (from-to)E8450-E8459
Number of pages10
JournalProceedings of the National Academy of Sciences
Issue number36
Publication statusPublished - 4 Sep 2018


  • Genomics
  • Great apes
  • Malaria
  • Plasmodium vivax
  • Zoonotic transmission


Dive into the research topics of 'Evolutionary history of human Plasmodium vivax revealed by genome-wide analyses of related ape parasites'. Together they form a unique fingerprint.

Cite this