title: Var Gene promoter activation in clonal Plasmodium falciparum isolates follows a hierarchy and suggests a conserved switching program that is independent of genetic background.
abstract: Antigenic variation of Plasmodium falciparum is mediated by a mutually exclusive expression mechanism that limits expression to an individual member of the multicopy var gene family. This process determines the antigenic and adhesive phenotype of the infected red blood cell. Previously, we showed that var gene switching is influenced by chromosomal position. Here, we address whether var gene transcription follows a general conserved pattern in long-term laboratory parasites and in recently culture-adapted field parasites. Activation of the var gene family was monitored in biological replicates in each parasite isolate every 3-5 generations for up to 3 months. We used transgenic parasites carrying a drug-selectable marker at a defined var locus to characterize var gene activation after the exclusive expression of the transgene. Transgenic parasites exhibited a repeatable hierarchy of var gene activation and a fluctuating transcriptional activity of the transgenic var locus. Transcriptional profiling of wild-type laboratory and field parasites showed a universal bias toward transcription of UpsC var genes and a fluctuating transcriptional activity of the dominant var promoter. The data suggest the existence of an intrinsic var gene transcription program that is independent of genetic background.
authors.affiliation: Institute of Tropical Medicine, University of Tuebingen, Tuebingen, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Enderes
authors.forename: Davy
authors.initials: D
authors.lastname: Kombila
authors.forename: Matthias
authors.initials: M
authors.lastname: Dal-Bianco
authors.forename: Ron
authors.initials: R
authors.lastname: Dzikowski
authors.forename: Peter
authors.initials: P
authors.lastname: Kremsner
authors.forename: Matthias
authors.initials: M
authors.lastname: Frank
mesh_terms: D000953:Antigens, Protozoan / Q000096:biosynthesis* / Q000235:genetics*; D001483:Base Sequence; D008969:Molecular Sequence Data; D030781:Organisms, Genetically Modified; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology*; D011401:Promoter Regions, Genetic; D015800:Protozoan Proteins / Q000096:biosynthesis* / Q000235:genetics*; D016053:RNA, Protozoan; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA; D014158:Transcription, Genetic
chemical_list: D000953:Antigens, Protozoan; D015800:Protozoan Proteins; D016053:RNA, Protozoan; C085731:erythrocyte membrane protein 1, Plasmodium falciparum