Co-ordinated programme of gene expression during asexual intraerythrocyticdevelopment of the human malaria parasite Plasmodium falciparum revealed by microarray analysis

Plasmodium falciparum is a protozoan parasite responsible for the most seve re forms of human malaria. All the clinical symptoms and pathological chang es seen during human infection are caused by the asexual blood stages of Pl asmodium. Within host red blood cells, the parasite undergoes enormous deve lopmental changes during its maturation. In order to analyse the expression of genes during intraerythrocytic development, DNA microarrays were constr ucted and probed with stage-specific cDNA. Developmental upregulation of sp ecific mRNAs was found to cluster into functional groups and revealed a co- ordinated programme of gene expression. Those involved in protein synthesis (ribosomal proteins, translation factors) peaked early in development, fol lowed by those involved in metabolism, most dramatically glycolysis genes. Adhesion/invasion genes were turned on later in the maturation process. At the end of intraerythrocytic development (late schizogony), there was a gen eral shut-off of gene expression, although a small set of genes, including a number of protein kinases, were turned on at this stage. Nearly all genes showed some regulation over the course of development. A handful of genes remained constant and should be useful for normalizing mRNA levels between stages. These data will facilitate functional analysis of the P. falciparum genome and will help to identify genes with a critical role in parasite pr ogression and multiplication in the human host.