Journal
JOURNAL OF MOLECULAR BIOLOGY
Volume 389, Issue 3, Pages 453-469Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2009.04.032
Keywords
malaria; recombination; var; switch; transcription
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The Plasmodium falciparum var multigene family encodes P. falciparum erythrocyte membrane protein 1, which is responsible for the pathogenic traits of antigenic variation and adhesion of infected erythrocytes to host receptors during malaria infection. Clonal antigenic variation of P falciparum erythrocyte membrane protein 1 is controlled by the switching between exclusively transcribed var genes. The tremendous diversity of the var gene repertoire both within and between parasite strains is critical for the parasite's strategy of immune evasion. We show that ectopic recombination between var genes occurs during mitosis, providing P. falciparum with opportunities to diversify its var repertoire, even during the course of a single infection. We show that the regulation of the recombined var gene has been disrupted, resulting in its persistent activation although the regulation of most other var genes is unaffected. The var promoter and intron of the recombined var gene are not responsible for its atypically persistent activity, and we conclude that altered subtelomeric cis sequel-ice is the most likely cause of the persistent activity of the recombined var gene. (C) 2009 Elsevier Ltd. All rights reserved.
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