SEQUENCE, TRANSCRIPT CHARACTERIZATION AND POLYMORPHISMS OF A PLASMODIUM-FALCIPARUM GENE BELONGING TO THE HEAT-SHOCK PROTEIN (HSP)90 FAMILY

A gene (pfhsp86) encoding a member of the heat-shock protein 90 (HSP90) family has been isolated from Plasmodium falciparum (Pf). The pfhsp86 coding region comprises two exons separated by an 0.8-kb intron with consensus splice junction sequences. The transcript itself is 3.4-kb long and includes a 0.65-kb 5'-untranslated region (UTR) and a 0.54-kb 3'-UTR. Upstream of the transcription start point (tsp) are putative promoter modules: an inverted CCAAT box, a G+C-rich sequence and several TATA sequences. Transcription is enhanced in erythrocyte-stage parasites cultivated at elevated temperatures (2-3-fold at 39 degrees C and 3-4-fold at 41 degrees C, relative to 37 degrees C). The pfhsp86 gene maps within a chromosome 7 segment that is linked to chloroquine (Cq) response in a Pf cross. The parents of this cross (Dd2, HB3) differ in the first exon by two trinucleotide repeats, while more divergence is apparent between the introns. These trinucleotide repeat differences are linked to Cq response in the HB3 x Dd2 cross, but they did not predict Cq response in nine Pf lines from different locations.