Plasmodium falciparum var gene expression is developmentally controlled at the level of RNA polymerase II-mediated transcription initiation

The Plasmodium falciparum var gene family codes for a major virulence factor in this most lethal of human malaria parasites. A single var protein variant type is expressed on each infected red blood cell, with antigenic variation allowing progeny parasites to escape host immune detection. The control of mutually exclusive var gene expression in the parasite relies on in situ epigenetic changes. Whether control of expression occurs at transcription initiation or post transcription, however, remains to be established. Recent evidence supports existence of a unique var transcription site at the nuclear periphery containing the dominantly expressed var gene, although silent var genes can colocalize to the same region. We demonstrate here that exclusive var gene expression is controlled at the level of transcription initiation during ring stages and that var genes are transcribed by RNA polymerase II. This represents another example where P. falciparum differs from the paradigm for antigenic variation, Trypanosoma brucei.