title: Plasmodium falciparum gametocyte development 1 (Pfgdv1) and gametocytogenesis early gene identification and commitment to sexual development.
abstract: 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 Plasmodium falciparumgametocyte development 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 gametocytogenesis early 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.
authors.affiliation: Department of Biology, Loyola University Chicago, Chicago, Illinois, USA.
authors.forename: Saliha
authors.initials: S
authors.lastname: Eksi
authors.forename: Belinda J
authors.initials: BJ
authors.lastname: Morahan
authors.forename: Yoseph
authors.initials: Y
authors.lastname: Haile
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Furuya
authors.forename: Hongying
authors.initials: H
authors.lastname: Jiang
authors.forename: Omar
authors.initials: O
authors.lastname: Ali
authors.forename: Huichun
authors.initials: H
authors.lastname: Xu
authors.forename: Kirakorn
authors.initials: K
authors.lastname: Kiattibutr
authors.forename: Amreena
authors.initials: A
authors.lastname: Suri
authors.forename: Beata
authors.initials: B
authors.lastname: Czesny
authors.forename: Adebowale
authors.initials: A
authors.lastname: Adeyemo
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Myers
authors.forename: Jetsumon
authors.initials: J
authors.lastname: Sattabongkot
authors.forename: Xin-zhuan
authors.initials: XZ
authors.lastname: Su
authors.forename: Kim C
authors.initials: KC
authors.lastname: Williamson
mesh_terms: D018507:Gene Expression Regulation, Developmental; D017125:Genes, Protozoan; D006801:Humans; D008288:Malaria / Q000469:parasitology* / Q000635:transmission; D018512:Parasitemia; D010963:Plasmodium falciparum / Q000235:genetics* / Q000254:growth & development* / Q000378:metabolism; D015800:Protozoan Proteins / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D012100:Reproduction, Asexual; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: D015800:Protozoan Proteins