GDV1 induces sexual commitment of malaria parasites by antagonizing HP1-dependent gene silencing

Abstract

Malaria is caused by <i>Plasmodium</i> parasites that proliferate in the bloodstream. During each replication cycle, some parasites differentiate into gametocytes, the only forms able to infect the mosquito vector and transmit malaria. Sexual commitment is triggered by activation of AP2-G, the master transcriptional regulator of gametocytogenesis. Heterochromatin protein 1 (HP1)-dependent silencing of <i>ap2-g</i> prevents sexual conversion in proliferating parasites. In this study, we identified <i>Plasmodium falciparum</i> gametocyte development 1 (GDV1) as an upstream activator of sexual commitment. We found that GDV1 targeted heterochromatin and triggered HP1 eviction, thus derepressing <i>ap2-g</i> Expression of GDV1 was responsive to environmental triggers of sexual conversion and controlled via a <i>gdv1</i> antisense RNA. Hence, GDV1 appears to act as an effector protein that induces sexual differentiation by antagonizing HP1-dependent gene silencing.