Combinatorial gene regulation in Plasmodium falciparum

The malaria parasite Plasmodium falciparum has a complicated life cycle with large variations in its gene expression pattern, but it contains relatively few specific transcriptional regulators. To elucidate this paradox, we identified regulatory sequences, using an approach that integrates the sequence conservation among species and the correlation in mRNA expression within a species. Our analysis identified several DNA sequence motifs that are associated with mRNA expression, two of which were previously determined experimentally. We found more putative regulatory sequences per gene in P. falciparum than in other eukaryotes, such as yeast. We propose that Plasmodium uses the few regulatory proteins it has in a combinatorial approach for gene regulation, explaining the relative paucity in regulatory proteins.