Molecular complexity of sexual development and gene regulation in Plasmodium falciparum

The malaria parasite, Plasmodium falciparum, has a complex life cycle which alternates between the vertebrate host and the invertebrate vector. Various morphological changes as well as stage-specific transcripts and gene expression profiles that accompany parasite's asexual and sexual life cycle suggest that gene regulation is crucial for the parasite's continual adaptations to survive the changing environments as well as for pathogenesis. Development of sexual stages is crucial for malaria transmission and relatively little is known about the role of specific gene products during asexual to sexual differentiation and further development. Therefore, in order to have a full understanding of the biology of the malaria parasite, gene regulation on a genome-wide global level must be understood, an area remaining to be elucidated in P. falciparum. Parasite features, such as A–T bias, difficulties in cloning, labor-intensive culture and purification of specific stages of the parasite, all contribute to the difficulties to investigate many aspects of parasite biology. However, despite these challenges, limited studies have revealed a number of parallelisms with eukaryotic transcription. For example, the parasite's genes are organised in a similar fashion, contain promoter elements and upstream activation sequences, as shown by structural searches and functional assays, and some of the basal machinery and general transcription factors have been found in Plasmodium. The completion of the full genome sequence of P. falciparum and other species of Plasmodium has resulted in the search for specific transcription factors through genome mining. Although genome mining may identify some of the factors, search for these factors solely by primary sequence homology would result in a non-comprehensive list for transcription factors present in the genome. Here, we present further discussion on putative transcription factors like activities detected in the asexual and sexual stages of P. falciparum.