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Frequent ectopic recombination of virulence factor genes in telomeric chromosome clusters of P. falciparum

Nature volume 407, pages 1018–1022 (2000)Cite this article

Abstract

Persistent and recurrent infections by Plasmodium falciparum malaria parasites result from the ability of the parasite to undergo antigenic variation and evade host immune attack1,2. P. falciparum parasites generate high levels of variability in gene families that comprise virulence determinants of cytoadherence and antigenic variation3,4,5,6,7, such as the var genes. These genes encode the major variable parasite protein (PfEMP-1), and are expressed in a mutually exclusive manner at the surface of the erythrocyte infected by P. falciparum8,9,10,11,12. Here we identify a mechanism by which var gene sequences undergo recombination at frequencies much higher than those expected from homologous crossover events alone13. These recombination events occur between subtelomeric regions of heterologous chromosomes, which associate in clusters near the nuclear periphery in asexual blood-stage parasites or in bouquet-like configurations near one pole of the elongated nuclei in sexual parasite forms. We propose that the alignment of var genes in heterologous chromosomes facilitates gene conversion and promotes the diversity of antigenic and adhesive phenotypes. The association of virulence factors with a specific nuclear subcompartment may also have implications for variation during mitotic recombination in asexual blood stages.

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Figure 1: Frequent ectopic recombination events between members of the var gene family during sexual reproduction.
Figure 2: Ectopic gene conversion in progeny from the HB3×Dd2 and HB3×3D7 crosses.
Figure 3: Physical clustering of P. falciparum subtelomeric regions detected in sexual and asexual parasites.
Figure 4: Promiscuous bouquet formation of P. falciparum chromosome ends.

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Acknowledgements

We thank C. Roth for critically reading the manuscript, D. Mattei for providing the Pf332 probes, V. Galy for help with the colocalization studies and D. Walliker for the progeny clones of the HB3×3D7 cross. This work has been supported by grants from the Commission of the European Communities for research and technical development. L.H.F.-J. was supported by a Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) fellowship. L.A.P. was supported by a European Community grant.

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Author notes

  1. Francoise Guinet

    Present address: Bactériologie Moléculaire et Médicale, Institut Pasteur, 25 rue du Dr Roux, 75724, Paris, Cedex 15, France

  2. Emmanuel Bottius

    Present address: Gen Odyssee, Les Ulis, 91974, Courtaboeuf Cedex, France

Authors and Affiliations

  1. Unité de Biologie des Interactions Hote-Parasite, CNRS URA 1960,

    Lúcio H. Freitas-Junior, Emmanuel Bottius, Lindsay A. Pirrit, Christine Scheidig, Francoise Guinet & Artur Scherf

  2. Laboratoire de Biologie Cellulaire du Noyau, CNRS URA 1773, Institut Pasteur, 25 rue du Dr Roux, Paris, 75724 Cedex 15, France

    Ulf Nehrbass

  3. Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892-0425, Maryland, USA

    Kirk W. Deitsch & Thomas E. Wellems

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  1. Lúcio H. Freitas-Junior
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Correspondence to Artur Scherf.

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Freitas-Junior, L., Bottius, E., Pirrit, L. et al. Frequent ectopic recombination of virulence factor genes in telomeric chromosome clusters of P. falciparum. Nature 407, 1018–1022 (2000). https://doi.org/10.1038/35039531

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