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Proc Natl Acad Sci U S A. 2018 Sep 4;115(36):E8450-E8459. doi: 10.1073/pnas.1810053115. Epub 2018 Aug 20.

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

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Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104.
Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3FL, United Kingdom.
Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh EH9 3FL, United Kingdom.
Walter and Eliza Hall Institute of Medical Research, Parkville VIC 3052, Australia.
Department of Medical Biology, The University of Melbourne, Parkville VIC 3010, Australia.
Robert Koch Institute, 13353 Berlin, Germany.
Sanaga-Yong Chimpanzee Rescue Center, International Development Association-Africa, Portland, OR 97208.
Recherche Translationnelle Appliquée au VIH et aux Maladies Infectieuses, Institut de Recherche pour le Développement, University of Montpellier, INSERM, 34090 Montpellier, France.
Malaria Programme, Wellcome Trust Sanger Institute, Genome Campus, Hinxton Cambridgeshire CB10 1SA, United Kingdom.
Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104;


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.


Plasmodium vivax; genomics; great apes; malaria; zoonotic transmission

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