Identification of regulatory elements in the Plasmodium falciparum genome.

There is little information regarding regulatory sequences in the newly sequenced genome of the malaria parasite, Plasmodium falciparum. Thus, for the first time, a bioinformatic strategy was utilized to identify regulatory elements in this genome using the P. falciparum heat shock protein (hsp) gene family as a model system. Our analysis indicates that the P. falciparum hsp genes do not contain standard eukaryotic regulatory elements. However, a novel G-rich regulatory element named the G-box was identified upstream of several P. falciparum hsp genes and the P. yoelii yoelii, P. berghei, and P. vivax hsp86 genes. Remarkably, the Plasmodium sp. G-boxes were required for maximal reporter gene expression in transient transfection assays. The G-box is not homologous to known eukaryotic elements, and is the best-defined functional element elucidated from Plasmodium sp. Our analysis also revealed several other elements necessary for reporter gene expression including an upstream sequence element, the region surrounding the transcription start site, and the 5' and 3' untranslated regions. These data demonstrate that unique regulatory elements are conserved in the genomes of Plasmodium sp., and demonstrate the feasibility of bioinformatic approaches for their identification.