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Ectopic recombination of a malaria var gene during mitosis associated with an altered var switch rate

Michael F Duffy1, Timothy J Byrne, Celine Carret

  • 1Department of Medicine at RMH, University of Melbourne, Parkville 3050, Australia. mduffy@unimelb.edu.au

Journal of Molecular Biology
|April 25, 2009
PubMed

Insights

Malaria parasites diversify their defense genes through recombination during mitosis. This process can lead to persistent activation of specific genes, aiding parasite immune evasion.

Area of Science:

  • Malariology
  • Molecular Parasitology
  • Genetics

Background:

  • The Plasmodium falciparum var multigene family encodes parasite proteins crucial for malaria pathogenesis.
  • These proteins mediate antigenic variation and adhesion, enabling parasite immune evasion.
  • Var gene repertoire diversity is key to Plasmodium falciparum's survival strategy.

Purpose of the Study:

  • To investigate mechanisms of var gene diversification in Plasmodium falciparum.
  • To understand the regulation of recombined var genes.
  • To identify factors contributing to atypical gene activation.

Main Methods:

  • Analysis of ectopic recombination events during Plasmodium falciparum mitosis.
  • Investigation of var gene regulation, including promoter and intron activity.
  • Assessment of subtelomeric cis sequences in recombined var genes.

Main Results:

  • Ectopic recombination between var genes occurs during Plasmodium falciparum mitosis.
  • Recombination provides opportunities for var gene repertoire diversification within infections.
  • A recombined var gene exhibited persistently altered regulation and activation.
  • The var promoter and intron were not responsible for the persistent activity.

Conclusions:

  • Mitotic recombination is a mechanism for diversifying the var gene repertoire in Plasmodium falciparum.
  • Altered subtelomeric cis sequences are the likely cause of persistent var gene activity.
  • These findings offer insights into parasite immune evasion strategies.

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