Sex in Plasmodium falciparum: Silence Play between GDV1 and HP1

Abstract

Understanding how malaria parasites commit to sexual development is key to the development of transmission-blocking strategies. Recent work by Filarsky and colleagues extends our understanding of the molecular mechanisms driving this process by characterizing an early factor in gametocytogenesis, and showing how this fits neatly into our current knowledge of sexual commitment.

Figure 1.. Regulation of Sexual Commitment in Human Malaria.

In parasites undergoing asexual development, the long noncoding gdv1 antisense RNA asgdv1 acts as a negative regulator of GDV1 expression. The lack of GDV1 allows HP1 and HDA2 to maintain a repressed chromatin state through H3K9 methylation and deacetylation at many loci, including that of AP2G. This prevents expression of AP2G, allowing continued asexual development. In a small subset of parasites, asgdv1 is somehow inactivated, either stochastically or following the transduction of various environmental signals, allowing expression of GDV1 and therefore eviction of HP1 from specific loci, including AP2G. Without HP1 to maintain H3K9 methylation, the chromatin returns to a euchromatic state, leading to the expression of AP2G and a resultant commitment to sexual development.