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

Author

Listed:
  • 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
    Gen Odyssee)

  • 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
    Institut Pasteur)

  • 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)

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.

Suggested Citation

  • Lúcio H. Freitas-Junior & Emmanuel Bottius & Lindsay A. Pirrit & Kirk W. Deitsch & Christine Scheidig & Francoise Guinet & Ulf Nehrbass & Thomas E. Wellems & Artur Scherf, 2000. "Frequent ectopic recombination of virulence factor genes in telomeric chromosome clusters of P. falciparum," Nature, Nature, vol. 407(6807), pages 1018-1022, October.
  • Handle: RePEc:nat:nature:v:407:y:2000:i:6807:d:10.1038_35039531
    DOI: 10.1038/35039531
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    Cited by:

    1. Caroline S. Meier & Marco Pagni & Sophie Richard & Konrad Mühlethaler & João M. G. C. F. Almeida & Gilles Nevez & Melanie T. Cushion & Enrique J. Calderón & Philippe M. Hauser, 2023. "Fungal antigenic variation using mosaicism and reassortment of subtelomeric genes’ repertoires," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Chung Hyun Cho & Seung In Park & Tzu-Yen Huang & Yongsung Lee & Claudia Ciniglia & Hari Chandana Yadavalli & Seong Wook Yang & Debashish Bhattacharya & Hwan Su Yoon, 2023. "Genome-wide signatures of adaptation to extreme environments in red algae," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. Qi Zhan & Qixin He & Kathryn E. Tiedje & Karen P. Day & Mercedes Pascual, 2024. "Hyper-diverse antigenic variation and resilience to transmission-reducing intervention in falciparum malaria," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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