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

Matthias Frank, Ron Dzikowski, Borko Amulic, Kirk Deitsch

Research output: Contribution to journalArticle (Academic Journal)peer-review

80 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1486-98
Number of pages13
JournalMolecular Microbiology
Volume64
Issue number6
DOIs
Publication statusPublished - Jun 2007

Keywords

  • Animals
  • Antigenic Variation
  • Chromosome Mapping
  • Chromosomes
  • Culture Media
  • Gene Expression Regulation
  • Genetic Variation
  • Humans
  • Malaria, Falciparum
  • Plasmodium falciparum
  • Promoter Regions, Genetic
  • Protozoan Proteins
  • Telomere
  • Transcription, Genetic
  • Transcriptional Activation
  • Transgenes
  • Virulence
  • Journal Article
  • Research Support, N.I.H., Extramural

Fingerprint

Dive into the research topics of 'Variable switching rates of malaria virulence genes are associated with chromosomal position'. Together they form a unique fingerprint.

Cite this