title: Genomic distribution and functional characterisation of two distinct and conserved Plasmodium falciparum var gene 5' flanking sequences.
abstract: Approximately 50 highly diverse var genes distributed throughout the haploid genome of the malaria parasite Plasmodium falciparum code for PfEMP1 variants located on the surface of infected erythrocytes. PfEMP1 is involved in cytoadherence of parasitised red blood cells and undergoes antigenic variation through differential expression of var genes. Members of the var gene family are located in chromosome-internal positions on chromosomes 4, 7, 8 and 12, and in subtelomeric regions of all chromosomes. Here we show that there are two distinct and conserved types of 5' upstream regions (var17-type and 5B1-type) of var genes, and suggest that most subtelomeric var genes are flanked by a var17-type 5' upstream sequence. In contrast, 5B1-type 5' upstream are localised to chromosomes that have been shown to contain var genes within chromosome-internal regions. Transcriptional analysis using RT-PCR revealed that var genes flanked by either type of 5' upstream sequence are transcribed in in vitro cultured trophozoite stage parasites. In addition, we have shown that the 5' flanking sequences of four different var genes are able to drive transient expression of the cat reporter gene. Our results suggest that at least the minimal regulatory sequences required for transcription of var genes are conserved among both subgroups of the var gene family. Furthermore, these sequences provide new markers for the investigation of the chromosomal organisation of var genes.
authors.affiliation: Swiss Tropical Institute, Socinstrasse 59, 4051, Basel, Switzerland. till.voss@unibas.ch
authors.forename: T S
authors.initials: TS
authors.lastname: Voss
authors.forename: J K
authors.initials: JK
authors.lastname: Thompson
authors.forename: J
authors.initials: J
authors.lastname: Waterkeyn
authors.forename: I
authors.initials: I
authors.lastname: Felger
authors.forename: N
authors.initials: N
authors.lastname: Weiss
authors.forename: A F
authors.initials: AF
authors.lastname: Cowman
authors.forename: H P
authors.initials: HP
authors.lastname: Beck
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics*; D000818:Animals; D000940:Antigenic Variation; D001483:Base Sequence; D017124:Conserved Sequence / Q000235:genetics*; D018503:Genome, Protozoan; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics* / Q000254:growth & development / Q000502:physiology; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
chemical_list: D020121:5' Untranslated Regions