The Transcriptome of the Intraerythrocytic Developmental Cycle of Plasmodium falciparum

By Zbynek Bozdech, M. Llinás, B. Pulliam, E. Wong, Jingchun Zhu, J. Derisi. PLoS Biology, 2003

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Plasmodium falciparum is the causative agent of the most burdensome form of human malaria, affecting 200–300 million individuals per year worldwide. The recently sequenced genome of P. falciparum revealed over 5,400 genes, of which 60% encode proteins of unknown function. Insights into the biochemical function and regulation of these genes will provide the foundation for future drug and vaccine development efforts toward eradication of this disease. By analyzing the complete asexual intraerythrocytic developmental cycle (IDC) transcriptome of the HB3 strain of P. falciparum, we demonstrate that at least 60% of the genome is transcriptionally active during this stage. Our data demonstrate that this parasite has evolved an extremely specialized mode of transcriptional regulation that produces a continuous cascade of gene expression, beginning with genes corresponding to general cellular processes, such as protein synthesis, and ending with Plasmodium-specific functionalities, such as genes involved in erythrocyte invasion. The data reveal that genes contiguous along the chromosomes are rarely coregulated, while transcription from the plastid genome is highly coregulated and likely polycistronic. Comparative genomic hybridization between HB3 and the reference genome strain (3D7) was used to distinguish between genes not expressed during the IDC and genes not detected because of possible sequence variations. Genomic differences between these strains were found almost exclusively in the highly antigenic subtelomeric regions of chromosomes. The simple cascade of gene regulation that directs the asexual development of P. falciparum is unprecedented in eukaryotic biology. The transcriptome of the IDC resembles a “just-in-time” manufacturing process whereby induction of any given gene occurs once per cycle and only at a time when it is required. These data provide to our knowledge the first comprehensive view of the timing of transcription throughout the intraerythrocytic development of P. falciparum and provide a resource for the identification of new chemotherapeutic and vaccine candidates.

Subfields: Immunology, Molecular Biology, Public Health, Environmental and Occupational Health

View Paper: https://www.semanticscholar.org/paper/26afb584b2803bb391b3e92c66f01281db718ef2

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Citations in the corpus

The s48/45 six-cysteine proteins: mediators of interaction throughout the Plasmodium life cycle (2016, background): “P38 is reported to be expressed in schizonts, sexual stages and sporozoites by several transcriptomic and proteomic studies (Bozdech et al., 2003; Le Roch et al., 2003; Gilson et al., 2006; Silvestrini et al., 2010; Lindner et al., 2013).”
INFERENCE FOR NORMAL MIXTURES IN MEAN AND VARIANCE (2008, background): “presented in Bozdech, Llinas, Pulliam, Wong, Zhu and DeRisi (2003) .”
Antimalarial drug discovery: efficacy models for compound screening (2004, background): “The former offer the opportunity to survey transcription across the plasmodial life cycl”
Recent Developments in Parameter Estimation and Structure Identification of Biochemical and Genomic Systems (2009, neutral): “, [61,113]).”
Strains and Strategies for Large-Scale Gene Deletion Studies of the Diploid Human Fungal Pathogen Candida albicans (2005, background): “Genome-scale studies and bioinformatics have already produced key scientific insights into mechanisms of pathogenesis (7, 13).”
Gametogenesis in Plasmodium: Delving Deeper to Connect the Dots (2022, background): “A highly co-regulated and coordinated expression of genes during the intra-erythrocytic developmental cycle governs DNA replication (Bozdech et al., 2003).”
A universal framework for regulatory element discovery across all genomes and data types. (2007, background): “Plasmodium falciparum Intraerythrocytic Developmental Cycle During the 48 hr intraerythrocytic developmental cycle (IDC) of the malaria parasite Plasmodium falciparum, 2700 of its genes exhibit a remarkably periodic expression pattern, characterized by an expression peak at a particular time point d”
A Systematic Map of Genetic Variation in Plasmodium falciparum (2006, positive): “Real-time PCR analysis of the GTP-cyclohydrolase gene (PFL1155w), along with a b-tubulin control gene (PF10_0084), confirmed the independent amplification of this gene in 3D7 and in the P. falciparum strains W2, HB3, FCB, D6, 7G8, and Dd2 but not in FCR3 or any of the five strains isolated from Sene”
Comparative Genomics in Eukaryotes (2005, methodology): “Expression data on the mRNA and protein level have become available from the malaria parasite Plasmodium falciparum (Bozdech et al., 2003; Florens et al., 2002; Lasonder et al., 2002; Le Roch et al., 2003).”
Structure and evolution of transcriptional regulatory networks. (2004, neutral): “Further support for the above statement is provided by several parasitic eukaryotes, such as the apicomplexans, that lack the diverse panoply of transcription factors seen in the crown group eukaryotes, but have a well-developed apparatus for chromatin modification and basal transcription [34,35].”