Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

A superfamily of variant genes encoded in the subtelomeric region of Plasmodium vivax

Nature volume 410, pages 839–842 (2001)Cite this article

Abstract

The malarial parasite Plasmodium vivax causes disease in humans, including chronic infections and recurrent relapses, but the course of infection is rarely fatal1,2, unlike that caused by Plasmodium falciparum. To investigate differences in pathogenicity between P. vivax and P. falciparum, we have compared the subtelomeric domains in the DNA of these parasites. In P. falciparum, subtelomeric domains are conserved and contain ordered arrays of members of multigene families, such as var3,4,5, rif6,7 and stevor8, encoding virulence determinants of cytoadhesion and antigenic variation. Here we identify, through the analysis of a continuous 155,711-base-pair sequence of a P. vivax chromosome end, a multigene family called vir, which is specific to P. vivax. The vir genes are present at about 600–1,000 copies per haploid genome and encode proteins that are immunovariant in natural infections, indicating that they may have a functional role in establishing chronic infection through antigenic variation.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Representation of the P. vivax telomeric YAC clone IVD10.
Figure 2: Organization of P. vivax vir genes: a representation of a consensus vir gene showing the 3-exon structure (open boxes) and the predicted transmembrane domain (hatched box).
Figure 3: Chromosomal distribution and expression of vir genes in P. vivax.
Figure 4: Immunodetection of VIR proteins in P. vivax. a, Purified total P. vivax blood stage antigens derived from two different patients (lanes Pv6 and Pv5) were analysed by western blot using a peptide antiserum to a semi-conserved motif of VIR subfamily D.

Similar content being viewed by others

References

  1. David, P. H., del Portillo, H. A. & Mendis, K. N. Plasmodium vivax malaria: parasite biology defines potential targets for vaccine development. Biol. Cell 64, 251–260 (1988).

    Article  CAS  Google Scholar 

  2. Galinski, M. R. & Barnwell, J. W. Plasmodium vivax: merozoites, invasion of reticulocytes and considerations for malaria vaccine development. Parasitol. Today 12, 20–29 (1996).

    Article  CAS  Google Scholar 

  3. Baruch, D. I. et al. Cloning of the P. falciparum gene encoding PfEMP1, a malarial variant antigen and adherence receptor on the surface of parasitized human erythrocytes. Cell 82, 77–87 (1995).

    Article  CAS  Google Scholar 

  4. Smith, J. D. et al. Switches in expression of Plasmodium falciparum var genes correlate with changes in antigenic and cytoadherent phenotypes of infected erythrocytes. Cell 82, 101–110 (1995).

    Article  CAS  Google Scholar 

  5. Su, X. et al. The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of Plasmodium falciparum-infected erythrocytes. Cell 82, 89–100 (1995).

    Article  CAS  Google Scholar 

  6. Kyes, S., Rowe, A. J., Kriek, N. & Newbold, C. I. Rifins: a second family of clonally variant proteins expressed on the surface of red cells infected with Plasmodium falciparum. Proc. Natl Acad. Sci. USA 96, 9333–9338 (1999).

    Article  ADS  CAS  Google Scholar 

  7. Fernandez, V., Hommel, M., Chen, Q., Hagblom, P. & Wahlgren, M. Small, clonally variant antigens expressed on the surface of Plasmodium falciparum-infected erythrocyte are encoded by the rif gene family and are the target of human immune responses. J. Exp. Med. 190, 1393–1403 (1999).

    Article  CAS  Google Scholar 

  8. Cheng, Q. et al. stevor and rif are Plasmodium falciparum multicopy gene families which potentially encode variant antigens. Mol. Biochem. Parasitol. 97, 161–176 (1998).

    Article  CAS  Google Scholar 

  9. Golenda, C. F., Li, J. & Rosenberg, R. Continuous in vitro propagation of the malaria parasite Plasmodium vivax. Proc. Natl Acad. Sci. USA 94, 6786–6791 (1997).

    Article  ADS  CAS  Google Scholar 

  10. Camargo, A. A., Fischer, K., Lanzer, M. & del Portillo, H. A. Construction and characterization of a Plasmodium vivax genomic library in yeast artificial chromosomes. Genomics 42, 467–473 (1997).

    Article  CAS  Google Scholar 

  11. Ponzi, M., Pace, T., Dore, F. & Frontali, C. Identification of a telomeric DNA sequence in Plasmodium berghei. EMBO J. 4, 2991–2995 (1985).

    Article  CAS  Google Scholar 

  12. Vernick, K. D. & McCutchan, T. F. Sequence and structure of a Plasmodium falciparum telomere. Mol. Biochem. Parasitol. 28, 85–94 (1988).

    Article  CAS  Google Scholar 

  13. McCutchan, T. F., Dame, J. B., Miller, L. H. & Barnwell, J. Evolutionary relatedness of Plasmodium species as determined by the structure of DNA. Science 225, 808–811 (1984).

    Article  ADS  CAS  Google Scholar 

  14. Gardner, M. J. et al. Chromosome 2 sequence of the human malaria parasite Plasmodium falciparum. Science 282, 1126–1132 (1998).

    Article  ADS  CAS  Google Scholar 

  15. Bowman, S. et al. The complete nucleotide sequence of chromosome 3 of Plasmodium falciparum. Nature 400, 532–538 (1999).

    Article  ADS  CAS  Google Scholar 

  16. The C. elegans sequencing consortium. Genome sequence of the nematode C. elegans: a platform for investigating biology. Science 282, 2012–2018 (1998).

    Article  ADS  Google Scholar 

  17. Al-Khedery, B., Barnwell, J. W. & Galinski, M. R. Antigenic variation in malaria: a 3′ genomic alteration associated with the expression of a P. knowlesi variant antigen. Mol. Cell 3, 131–141 (1999).

    Article  CAS  Google Scholar 

  18. Persson, B. Bioinformatics in protein analysis. EXS 88, 215–131 (2000).

    CAS  PubMed  Google Scholar 

  19. Mendis, K. N., Ihalamulla, R. I. & David, P. H. Diversity of Plasmodium vivax-induced antigens on the surface of infected human erythrocytes. Am. J. Trop. Med. Hyg. 38, 42–46 (1988).

    Article  CAS  Google Scholar 

  20. Freitas-Junior, L. H. et al. Frequent ectopic recombination of virulence factor genes in telomeric chromosome clusters of P. falciparum. Nature 407, 1018–1022 (2000).

    Article  ADS  CAS  Google Scholar 

  21. Vaudin, M. et al. The construction and analysis of M13 libraries prepared from YAC DNA. Nucleic Acids Res. 23, 670–674 (1995).

    Article  CAS  Google Scholar 

  22. Kyes, S., Pinches, R. & Newbold, C. A simple RNA analysis method shows var and rif multigene family expression patterns in Plasmodium falciparum. Mol Biochem. Parasitol. 105, 311–315 (2000).

    Article  CAS  Google Scholar 

  23. Levitus, G. et al. Characterization of naturally acquired human IgG responses against the N-terminal region of the merozoite surface protein 1 of Plasmodium vivax. Am. J. Trop. Med. Hyg. 51, 68–76 (1994).

    Article  CAS  Google Scholar 

  24. Hall, R. et al. Major surface antigen gene of a human malaria parasite cloned and expressed in bacteria. Nature 311, 379–382 (1984).

    Article  ADS  CAS  Google Scholar 

  25. Oliveira, C. I. et al. Antigenic properties of the Merozoite Surface Protein 1 gene of Plasmodium vivax. Vaccine 17, 2959–2968 (1999).

    Article  Google Scholar 

  26. Voller, A. & O'Neill, P. O. Immunofluorescence method suitable for large scale application to malaria. Bull. World Health Organ. 45, 524–529 (1971).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank all the patients who participated in this study; J. d'Arc Neves for collecting blood samples; A. Craig for helping in the initial liasion with the Sanger Centre; M. Quail and the subcloning group; members of team 23 and other members of the Pathogen Unit at the Sanger Centre for their help in sequence generation and analysis; N. Hall for the creation of the web pages; Y. Cully for the graphics; and H. Bujard for encouragement throughout this work. This work was supported by the the Deutsche Forschungsgemeinschaft (to M.L.) and the European Commission (to M.L. and H.A.P).

Author information

Authors and Affiliations

  1. Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Av. Lineu Prestes 1374, São Paulo, SP 05508-900, Brazil

    Hernando A. del Portillo & Carmen Fernandez-Becerra

  2. Pathogen Sequencing Unit, Sanger Centre, Wellcome Trust Genome Campus, Hinxton, CB10 1SA, UK

    Sharen Bowman, Karen Oliver, Marie-Adele Rajandream, David Harris & Bart Barrell

  3. Abteilung Parasitologie, Hygiene-Institut, Universität Heidelberg, INF 324, Heidelberg, D-69120, Germany

    Martin Preuss, Cecilia P. Sanchez, Nick K. Schneider & Michael Lanzer

  4. Centro de Pesquisa em Medicina Tropical (CEPEM) , Estrada BR 364 – Km 4,5, Porto Velho, Rondônia, 78900-000, Brazil

    Juan M. Villalobos & Luiz H. Pereira da Silva

Authors
  1. Hernando A. del Portillo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carmen Fernandez-Becerra
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sharen Bowman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Karen Oliver
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Martin Preuss
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Cecilia P. Sanchez
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nick K. Schneider
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Juan M. Villalobos
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Marie-Adele Rajandream
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. David Harris
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Luiz H. Pereira da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Bart Barrell
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Michael Lanzer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hernando A. del Portillo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

del Portillo, H., Fernandez-Becerra, C., Bowman, S. et al. A superfamily of variant genes encoded in the subtelomeric region of Plasmodium vivax. Nature 410, 839–842 (2001). https://doi.org/10.1038/35071118

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/35071118

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing