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Malaria transmission requires the production of male and female gametocytes in the human host followed by fertilization and sporogonic development in the mosquito midgut. Although essential for the spread of malaria through the population, little is known about the initiation of gametocytogenesis  in vitro  or  in vivo . Using a gametocyte-defective parasite line and genetic complementation, we show that   P lasmodium  f alciparum   g ametocyte  d evelopment 1 gene ( Pfgdv1) , encoding a peri-nuclear protein, is critical for early sexual differentiation. Transcriptional analysis of  Pfgdv1  negative and positive parasite lines identified a set of  g ametocytogenesis  e arly genes ( Pfge ) that were significantly down-regulated (>10 fold) in the absence of  Pfgdv1  and expression was restored after  Pfgdv1  complementation. Progressive accumulation of  Pfge  transcripts during successive rounds of asexual replication in synchronized cultures suggests that gametocytes are induced continuously during asexual growth. Comparison of  Pfge  gene transcriptional profiles in patient samples divided the genes into two groups differing in their expression in mature circulating gametocytes and providing candidates to evaluate gametocyte induction and maturation separately  in vivo . The expression profile of one of the early gametocyte specific genes,  Pfge1 , correlated significantly with asexual parasitemia, which is consistent with the ongoing induction of gametocytogenesis during asexual growth observed  in vitro  and reinforces the need for sustained transmission-blocking strategies to eliminate malaria.

Plasmodium falciparum Gametocyte Development 1 (Pfgdv1) and Gametocytogenesis Early Gene Identification and Commitment to Sexual Development