Variable switching rates of malaria virulence genes are associated with chromosomal position

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書誌事項

公開日
2007-06
権利情報
  • http://onlinelibrary.wiley.com/termsAndConditions#vor
DOI
  • 10.1111/j.1365-2958.2007.05736.x
公開者
Wiley

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<jats:title>Summary</jats:title><jats:p>Antigenic variation in <jats:italic>Plasmodium falciparum</jats:italic> malaria is mediated by transcriptional switches between different members of the multicopy <jats:italic>var</jats:italic> gene family. Each <jats:italic>var</jats:italic> gene encodes a member of a group of heterogeneous surface proteins collectively referred to as PfEMP1. Mutually exclusive expression ensures that an individual parasite only transcribes a single <jats:italic>var</jats:italic> gene at a time. In this work we studied <jats:italic>var</jats:italic> gene switching to determine if transcriptional switches favour expression of particular subgroups of <jats:italic>var</jats:italic> genes and if <jats:italic>var</jats:italic> gene activation within a clonal population of parasites follows a predetermined order. We show that in clonal parasite populations, expression of <jats:italic>var</jats:italic> genes located in the central regions of chromosomes is remarkably stable and that they rarely undergo transcriptional switches in the absence of selection. In contrast, parasites expressing subtelomerically located <jats:italic>var</jats:italic> genes readily switched to alternative <jats:italic>var</jats:italic> loci. We confirmed these observations by generating transgenic parasites carrying drug selectable markers in subtelomeric and central <jats:italic>var</jats:italic> loci and monitoring switching after release from selection. Our data show that different <jats:italic>var</jats:italic> genes have different intrinsic switching rates that correlate with chromosomal location, and that there is no predetermined order of expression.</jats:p>

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