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The malaria parasite Plasmodium vivax exhibits greater genetic diversity than Plasmodium falciparum

Nature Genetics volume 44, pages 1046–1050 (2012)Cite this article

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Abstract

We sequenced and annotated the genomes of four P. vivax strains collected from disparate geographic locations, tripling the number of genome sequences available for this understudied parasite and providing the first genome-wide perspective of global variability in this species. We observe approximately twice as much SNP diversity among these isolates as we do among a comparable collection of isolates of P. falciparum, a malaria-causing parasite that results in higher mortality. This indicates a distinct history of global colonization and/or a more stable demographic history for P. vivax relative to P. falciparum, which is thought to have undergone a recent population bottleneck. The SNP diversity, as well as additional microsatellite and gene family variability, suggests a capacity for greater functional variation in the global population of P. vivax. These findings warrant a deeper survey of variation in P. vivax to equip disease interventions targeting the distinctive biology of this neglected but major pathogen.

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Figure 1: Disparity in SNP and microsatellite diversity between P. vivax and P. falciparum.
Figure 2: Neighbor-joining phylograms of P. vivax and P. falciparum constructed from presumably neutral SNPs occurring in fourfold-degenerate coding sites.
Figure 3: Diversity of P. vivax gene families.

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NCBI Reference Sequence

Sequence Read Archive

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Acknowledgements

This work has been funded, in whole or in part, by federal funds from the US National Institute of Allergy and Infectious Diseases (NIAID), the US National Institutes of Health (NIH) and the US Department of Health and Human Services, under contracts HHSN266200400001C and HHSN2722009000018C. We gratefully acknowledge the Indian Council of Medical Research for financial support of the Malaria Parasite Bank at the National Institute of Malaria Research, New Delhi, and the NIMR Director for providing all facilities. We thank the NIAID/National Human Genome Research Institute (NHGRI) Eukaryotic Pathogens and Disease Vectors Working Group and the Broad Institute Genome Sequencing Platform for significant contributions to this project. K.G. and L.Y. are supported by a Global Health Program grant from the Bill and Melinda Gates Foundation. A.A.E. is supported by a grant from the NIH (RO1GM084320), and J.M.C. and P.L.S. are supported by grant U19AI089676, an NIAID International Center of Excellence for Malaria Research. The content is soley the responsibility of the authors and does not necessarily represent the official views of the NIH.

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  1. Aditya P Dash

    Present address: Present address: World Health House, New Delhi, India.,

Authors and Affiliations

  1. Broad Institute, Cambridge, Massachusetts, USA

    Daniel E Neafsey, Kevin Galinsky, Rays H Y Jiang, Lauren Young, Sean M Sykes, Sakina Saif, Sharvari Gujja, Jonathan M Goldberg, Sarah Young, Qiandong Zeng, Sinéad B Chapman & Bruce W Birren

  2. National Institute of Malaria Research, Indian Council of Medical Research, Dwarka, New Delhi, India

    Aditya P Dash & Anupkumar R Anvikar

  3. Department of Biology, Center for Genomics and Systems Biology, New York University, New York, New York, USA

    Patrick L Sutton & Jane M Carlton

  4. Center for Evolutionary Medicine & Informatics, The Biodesign Institute, School of Life Sciences, Arizona State University, Tempe, Arizona, USA

    Ananias A Escalante

  5. Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA

    John W Barnwell

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Contributions

J.W.B. provided P. vivax strains, and A.R.A. and A.P.D. provided Indian P. falciparum material. S.M.S., S.S. and S.Y. performed genome assembly. S.G., J.M.G. and Q.Z. performed genome annotation. K.G., R.H.Y.J., L.Y. and D.E.N. performed analyses. S.B.C. performed project management. P.L.S. undertook experimental validation. D.E.N., A.A.E., B.W.B. and J.M.C. directed the analyses. D.E.N., A.A.E., J.W.B. and J.M.C. wrote the manuscript.

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Correspondence to Jane M Carlton.

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The authors declare no competing financial interests.

Supplementary Information for

The malaria parasite Plasmodium vivax exhibits greater genetic diversity than Plasmodium falciparum

41588_2012_BFng2373_MOESM19_ESM.xls

Comparison of nonsynomymous:synonymous diversity ratio (πN/πS) in P. vivax and P. falciparum orthologs (.xlsx file) (XLS 136 kb)

41588_2012_BFng2373_MOESM20_ESM.xls

Gene categories differentially enriched (Z > 2) for functional diversity (πN/πS) in P. vivax or P. falciparum (.xlsx file) (XLS 34 kb)

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Neafsey, D., Galinsky, K., Jiang, R. et al. The malaria parasite Plasmodium vivax exhibits greater genetic diversity than Plasmodium falciparum. Nat Genet 44, 1046–1050 (2012). https://doi.org/10.1038/ng.2373

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