Variable switching rates of malaria virulence genes are associated with chromosomal position.
Antigenic variation in Plasmodium falciparum malaria is mediated by transcriptional switches between different members of the multicopy var gene family. Each var 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 var gene at a time. In this work we studied var gene switching to determine if transcriptional switches favour expression of particular subgroups of var genes and if var gene activation within a clonal population of parasites follows a predetermined order. We show that in clonal parasite populations, expression of var 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 var genes readily switched to alternative var loci. We confirmed these observations by generating transgenic parasites carrying drug selectable markers in subtelomeric and central var loci and monitoring switching after release from selection. Our data show that different var genes have different intrinsic switching rates that correlate with chromosomal location, and that there is no predetermined order of expression.
Frank
Matthias
M
Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, box 62, New York, NY 10021, USA.
Dzikowski
Ron
R
Amulic
Borko
B
Deitsch
Kirk
K
D000818:Animals; D000940:Antigenic Variation; D002874:Chromosome Mapping; D002875:Chromosomes / Q000235:genetics; D003470:Culture Media; D005786:Gene Expression Regulation; D014644:Genetic Variation; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology; D010963:Plasmodium falciparum / Q000235:genetics / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D011401:Promoter Regions, Genetic; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism; D016615:Telomere; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D019076:Transgenes; D014774:Virulence / Q000235:genetics
D003470:Culture Media; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum