ArticleNature2014
A transcriptional switch underlies commitment to sexual development in malaria parasites.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 310 papers, 1 of them a synthesis that pooled it.
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Who cites it
310 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Protocols for Plasmodium gametocyte production in vitro: an integrative review and analysis.Parasites & vectors · 2022Pooled it
- Transmissibility of a new Plasmodium falciparum 3D7 bank for use in malaria volunteer infection studies evaluating transmission blocking interventions.Scientific reports · 2025Trial
- Trial
- A Randomized Clinical Trial to Compare Plasmodium falciparum Gametocytemia and Infectivity After Blood-Stage or Mosquito Bite-Induced Controlled Malaria Infection.The Journal of infectious diseases · 2021Trial
- AP2-HS and a GDV1 regulatory feedback loop mediate environmental induction of sexual conversion in Plasmodium falciparum.Nature microbiology · 2026Article
- Histone H2B monoubiquitination drives sexual commitment in malaria parasites.Nature microbiology · 2026Article
- TKL3 regulates blood-stage fitness, male gamete fertility, and transmission-stage development in Plasmodium berghei.PLoS pathogens · 2026Article
- Elevated Plasmodium falciparum sexual conversion in HbAC and HbAS red blood cells in naturally infected malaria patients.PLoS pathogens · 2026Article
- Single-Cell Transcriptomics and Development of Gametocyte-Specific Molecular Markers for Avian Malaria Parasites.Molecular ecology resources · 2026Article
- Single-cell analysis ofbioRxiv : the preprint server for biology · 2026Article
- A heterologous marker-free selection approach for CRISPR/Cas9-based gene editing in the malaria parasitemSphere · 2026Article
- Targeting protein-protein interactions in Plasmodium: from asexual replication to sexual development.Parasites & vectors · 2026Review
- GID/CTLH E3 ligase complex control cell fate programs for sexual development of Plasmodium falciparum.Nature communications · 2026Article
- A single valine to leucine switch disrupts Plasmodium falciparum AP2-G DNA binding and reveals GDV1's role in ap2-g activation.Nature communications · 2026Article
- Chromatin state dynamics during the Plasmodium falciparum intraerythrocytic development cycle.BMC genomics · 2026Article
- Precise gene regulation through transcriptional repression is essential for Plasmodium berghei asexual blood stage development.Nature communications · 2026Article
- Molecular mechanisms involved inFrontiers in microbiology · 2026Review
- Large-Scale Mutagenesis Screening for Genetic Determinants of Plasmodium falciparum Sexual Development.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Plasmodium knowlesi gametocyte carriage and load among malaria patients at Kapit Hospital in Sarawak, Malaysian Borneo.Scientific reports · 2025Article
- An ApiAP2 Family Transcriptional Factor PfAP2-06B Regulates Erythrocyte Invasion Indirectly inPathogens (Basel, Switzerland) · 2025Article
250 more citing papers are in PubMed but not listed here.
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12 authors.
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Abstract
The life cycles of many parasites involve transitions between disparate host species, requiring these parasites to go through multiple developmental stages adapted to each of these specialized niches. Transmission of malaria parasites (Plasmodium spp.) from humans to the mosquito vector requires differentiation from asexual stages replicating within red blood cells into non-dividing male and female gametocytes. Although gametocytes were first described in 1880, our understanding of the molecular mechanisms involved in commitment to gametocyte formation is extremely limited, and disrupting this critical developmental transition remains a long-standing goal. Here we show that expression levels of the DNA-binding protein PfAP2-G correlate strongly with levels of gametocyte formation. Using independent forward and reverse genetics approaches, we demonstrate that PfAP2-G function is essential for parasite sexual differentiation. By combining genome-wide PfAP2-G cognate motif occurrence with global transcriptional changes resulting from PfAP2-G ablation, we identify early gametocyte genes as probable targets of PfAP2-G and show that their regulation by PfAP2-G is critical for their wild-type level expression. In the asexual blood-stage parasites pfap2-g appears to be among a set of epigenetically silenced loci prone to spontaneous activation. Stochastic activation presents a simple mechanism for a low baseline of gametocyte production. Overall, these findings identify PfAP2-G as a master regulator of sexual-stage development in malaria parasites and mark the first discovery of a transcriptional switch controlling a differentiation decision in protozoan parasites.
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