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Genomes of all known members of a Plasmodium subgenus reveal paths to virulent human malaria

Nature Microbiology volume 3, pages 687–697 (2018)Cite this article

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Abstract

Plasmodium falciparum, the most virulent agent of human malaria, shares a recent common ancestor with the gorilla parasite Plasmodium praefalciparum. Little is known about the other gorilla- and chimpanzee-infecting species in the same (Laverania) subgenus as P. falciparum, but none of them are capable of establishing repeated infection and transmission in humans. To elucidate underlying mechanisms and the evolutionary history of this subgenus, we have generated multiple genomes from all known Laverania species. The completeness of our dataset allows us to conclude that interspecific gene transfers, as well as convergent evolution, were important in the evolution of these species. Striking copy number and structural variations were observed within gene families and one, stevor, shows a host-specific sequence pattern. The complete genome sequence of the closest ancestor of P. falciparum enables us to estimate the timing of the beginning of speciation to be 40,000–60,000 years ago followed by a population bottleneck around 4,000–6,000 years ago. Our data allow us also to search in detail for the features of P. falciparum that made it the only member of the Laverania able to infect and spread in humans.

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Fig. 1: Overview of the dating of the evolution of the Laverania.
Fig. 2: Overview of the analyses of core genes over all Laverania genomes.
Fig. 3: Gene families in the Laverania.
Fig. 4: Clustering of Pir (Rifin and Stevor) proteins families.
Fig. 5
Fig. 6: Overview of the genomic evolution of the Laverania subgenus.

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Acknowledgements

This work was funded by ANR ORIGIN JCJC 2012, LMI ZOFAC, CNRS, CIRMF, IRD, and the Wellcome Trust (grants WT 098051 and WT 206194 to the Sanger Institute, grant 104792/Z/14/Z to C.N.). T.C. holds an MRC DTP Studentship. We thank G. Rutledge for performing the sWGA and J. Rayner and F. J. Ayala for helpful discussion. We thank the PlasmoDB team for promptly making these data available.

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  1. Thomas D. Otto

    Present address: Centre of Immunobiology, Institute of Infection, Immunity & Inflammation, College of Medical, Veterinary and Life Sciences University of Glasgow, Glasgow, UK

  2. These authors contributed equally: T. D. Otto, A. Gilabert.

Authors and Affiliations

  1. Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, UK

    Thomas D. Otto, Thomas Crellen, Ulrike Böhme, Mandy Sanders, Samuel O. Oyola, Chris Newbold & Matthew Berriman

  2. Laboratoire MIVEGEC, UMR 5290-224 CNRS 5290-IRD224-UM, Montpellier, France

    Aude Gilabert, Céline Arnathau, Christophe Paupy, Patrick Durand, Virginie Rougeron, François Renaud & Franck Prugnolle

  3. Department of Infectious Disease Epidemiology, Imperial College London, London, UK

    Thomas Crellen

  4. International Livestock Research Institute, Nairobi, Kenya

    Samuel O. Oyola

  5. Centre International de Recherches Médicales de Franceville, Franceville, Gabon

    Alain Prince Okouga, Larson Boundenga, Barthélémy Ngoubangoye, Nancy Diamella Moukodoum, Virginie Rougeron, Benjamin Ollomo & Franck Prugnolle

  6. Sodepal, Parc of la Lékédi, Bakoumba, Gabon

    Eric Willaume

  7. Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK

    Chris Newbold

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Contributions

T.D.O., B.O., F.R., C.N., M.B. and F.P. designed the study. C.A., A.P.O., L.B., E.W., B.N., N.D.M., C.P., P.D., V.R. and F.P. collected and assessed samples. C.A. performed the WGA and cell sorting on one sample. S.O.O. performed the WGA on the samples. M.S. organized the sequencing. T.D.O. did assembly and annotation. U.B. did manual gene curation. A.G. and F.P. performed the evolutionary analyses on core genomes. T.D.O., C.N. and M.B. performed the analyses of gene families and dimorphisms. T.C. performed the dating analyses. T.D.O., A.G., C.N., M.B. and F.P. wrote the manuscript. All authors read and approved the paper.

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Otto, T.D., Gilabert, A., Crellen, T. et al. Genomes of all known members of a Plasmodium subgenus reveal paths to virulent human malaria. Nat Microbiol 3, 687–697 (2018). https://doi.org/10.1038/s41564-018-0162-2

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