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Letters to Nature

Nature 407, 1018-1022 (26 October 2000) | doi:10.1038/35039531; Received 8 August 2000; Accepted 13 September 2000

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

Lúcio H. Freitas-Junior1, Emmanuel Bottius1,2, Lindsay A. Pirrit1, Kirk W. Deitsch3, Christine Scheidig1, Francoise Guinet1,2, Ulf Nehrbass4, Thomas E. Wellems3 & Artur Scherf1

  1. Unité de Biologie des Interactions Hote-Parasite, CNRS URA 1960, and
  2. Laboratoire de Biologie Cellulaire du Noyau, CNRS URA 1773, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France
  3. Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0425, USA
  4. Present address: Bactériologie Moléculaire et Médicale, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France (F.G.); Gen Odyssee, Les Ulis 91974 Courtaboeuf Cedex, France (E.B.).

Correspondence to: Artur Scherf1 Correspondence and requests for materials should be addressed to A.S. (e-mail: Email: ascherf@pasteur.fr).

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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.