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

Lúcio H. Freitas-Junior, Emmanuel Bottius, Lindsay A. Pirrit, Kirk W. Deitsch, Christine Scheidig, Francoise Guinet, Ulf Nehrbass, Thomas E. Wellems and Artur Scherf ()
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Lúcio H. Freitas-Junior: Unité de Biologie des Interactions Hote-Parasite, CNRS URA 1960
Emmanuel Bottius: Unité de Biologie des Interactions Hote-Parasite, CNRS URA 1960
Lindsay A. Pirrit: Unité de Biologie des Interactions Hote-Parasite, CNRS URA 1960
Kirk W. Deitsch: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Christine Scheidig: Unité de Biologie des Interactions Hote-Parasite, CNRS URA 1960
Francoise Guinet: Unité de Biologie des Interactions Hote-Parasite, CNRS URA 1960
Ulf Nehrbass: Institut Pasteur
Thomas E. Wellems: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Artur Scherf: Unité de Biologie des Interactions Hote-Parasite, CNRS URA 1960

Nature, 2000, vol. 407, issue 6807, 1018-1022

Abstract: 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.

Date: 2000
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DOI: 10.1038/35039531

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