The Transcriptome of the Intraerythrocytic Developmental Cycle of Plasmodium falciparum
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{"title"=>"The transcriptome of the intraerythrocytic developmental cycle of Plasmodium falciparum", "type"=>"journal", "authors"=>[{"first_name"=>"Zbynek", "last_name"=>"Bozdech", "scopus_author_id"=>"7007157687"}, {"first_name"=>"Manuel", "last_name"=>"Llinás", "scopus_author_id"=>"12776054300"}, {"first_name"=>"Brian Lee", "last_name"=>"Pulliam", "scopus_author_id"=>"8581246000"}, {"first_name"=>"Edith D.", "last_name"=>"Wong", "scopus_author_id"=>"7403161510"}, {"first_name"=>"Jingchun", "last_name"=>"Zhu", "scopus_author_id"=>"23136066600"}, {"first_name"=>"Joseph L.", "last_name"=>"DeRisi", "scopus_author_id"=>"7004334309"}], "year"=>2003, "source"=>"PLoS Biology", "identifiers"=>{"pui"=>"39112195", "sgr"=>"4243071596", "pmid"=>"12929205", "scopus"=>"2-s2.0-4243071596", "isbn"=>"1545-7885 (Electronic)", "doi"=>"10.1371/journal.pbio.0000005", "issn"=>"15449173"}, "id"=>"e6884811-4c73-3fb4-afc1-ca90a4cd251e", "abstract"=>"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.", "link"=>"http://www.mendeley.com/research/transcriptome-intraerythrocytic-developmental-cycle-plasmodium-falciparum", "reader_count"=>555, "reader_count_by_academic_status"=>{"Unspecified"=>8, "Professor > Associate Professor"=>31, "Librarian"=>1, "Student > Doctoral Student"=>26, "Researcher"=>115, "Student > Ph. D. Student"=>153, "Student > Postgraduate"=>29, "Student > Master"=>76, "Other"=>20, "Student > Bachelor"=>61, "Lecturer"=>10, "Lecturer > Senior Lecturer"=>3, "Professor"=>22}, "reader_count_by_user_role"=>{"Unspecified"=>8, "Professor > Associate Professor"=>31, "Librarian"=>1, "Student > Doctoral Student"=>26, "Researcher"=>115, "Student > Ph. D. 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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/964615"], "description"=>"<div><p>(A) A phaseogram of the IDC transcriptome was created by ordering the transcriptional profiles for 2,712 genes by phase of expression along the y-axis. The characteristic stages of intraerythrocytic parasite morphology are shown on the left, aligned with the corresponding phase of peak gene expression.</p>\n <p>(B–M) The temporal ordering of biochemical processes and functions is shown on the right. Each graph corresponds to the average expression profile for the genes in each set and the mean peak-to-trough amplitude is shown in parentheses.</p></div>", "links"=>[], "tags"=>["idc"], "article_id"=>634546, "categories"=>["Microbiology", "Genetics", "Infectious Diseases"], "users"=>["Zbynek Bozdech", "Manuel Llinás", "Brian Lee Pulliam", "Edith D Wong", "Jingchun Zhu", "Joseph L DeRisi"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.0000005.g002", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Overview_of_the_P_falciparum_IDC_Transcriptome_/634546", "title"=>"Overview of the P. falciparum IDC Transcriptome", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 09:20:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/964422"], "description"=>"<div><p>(A) Giemsa stains of the major morphological stages throughout the IDC are shown with the percent representation of ring-, trophozoite-, or schizont-stage parasites at every timepoint. The 2-h invasion window during the initiation of the bioreactor culture is indicated (gray area).</p>\n <p>(B–D) Example expression profiles for three genes, encoding EBA175, DHFR-TS, and ASL, are shown with a loess fit of the data (red line).</p>\n <p>(E) MAL6P1.147, the largest predicted ORF in the <i>Plasmodium</i> genome, is represented by 14 unique DNA oligonucleotide elements. The location of each of the oligonucleotide elements within the predicted ORF and the corresponding individual expression profiles are indicated (oligo 1–14). A red/green colorimetric representation of the gene expression ratios for each oligonucleotide is shown below the graph. The pairwise Pearson correlation for these expression profiles is 0.98 ± 0.02.</p>\n <p>(F) The percentage of the power in the maximum frequency of the FFT power spectrum was used as an indicator of periodicity. A histogram of these values reveals a strong bias toward single-frequency expression profiles, indicating that the majority of P. falciparum genes are regulated in a simple periodic manner. This bias is eliminated when the percent power was recalculated using random permutations of the same dataset (inset). For reference, the locations of EBA175 (peak B), DHFR-TS (peak C), and ASL (peak D) are shown.</p></div>", "links"=>[], "tags"=>["culturing", "idc", "transcriptome"], "article_id"=>634355, "categories"=>["Microbiology", "Genetics", "Infectious Diseases"], "users"=>["Zbynek Bozdech", "Manuel Llinás", "Brian Lee Pulliam", "Edith D Wong", "Jingchun Zhu", "Joseph L DeRisi"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.0000005.g001", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Parasite_Culturing_and_Data_Characteristics_of_the_P_falciparum_IDC_Transcriptome_Analysis_/634355", "title"=>"Parasite Culturing and Data Characteristics of the P. falciparum IDC Transcriptome Analysis", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 09:18:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/964733"], "description"=>"<p>Expression profiles for oligonucleotides are shown as a function of location for Chromosome 2 ([A], Oligo Map). With the exception of the SERA locus (B), coregulated clusters of adjacent ORFs are seldom observed, indicating that expression phase is largely independent of chromosomal position. (C) In contrast to the nuclear chromosomes, the polycistronic expression of the circular plastid genome is reflected in the tight coregulation of gene expression. This is an expanded view of the plastid-encoded genes from <a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0000005#pbio-0000005-g002\" target=\"_blank\">Figure 2</a>J. Genomic differences between strain 3D7, from which the complete genome was sequenced, and strain HB3 were measured by CGH. The relative hybridization between the gDNA derived from these two strains is shown as a percent reduction of the signal intensity for 3D7 ([A],<b> </b> CGH Data). Differences between the two strains are predominately located in the subtelomeric regions that contain the highly polymorphic <i>var, rifin,</i> and <i>stevor</i> gene families. Intrachromosomal variations, as observed for the <i>msp2</i> gene, were rare.</p>", "links"=>[], "tags"=>["chromosomes", "plastid"], "article_id"=>634660, "categories"=>["Microbiology", "Genetics", "Infectious Diseases"], "users"=>["Zbynek Bozdech", "Manuel Llinás", "Brian Lee Pulliam", "Edith D Wong", "Jingchun Zhu", "Joseph L DeRisi"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.0000005.g003", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Coregulation_of_Gene_Expression_along_the_Chromosomes_of_P_falciparum_Is_Rare_While_Plastid_Gene_Expression_Is_Highly_Coordinated_/634660", "title"=>"Coregulation of Gene Expression along the Chromosomes of P. falciparum Is Rare, While Plastid Gene Expression Is Highly Coordinated", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 09:21:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/964796"], "description"=>"<div><p>(A) The expression profiles of all putative plastid-targeted genes represented on our microarray are shown. The yellow box encompasses a highly synchronized group of genes, which are in-phase with plastid genome expression. The average expression profile for this in-phase group of genes is shown and includes most of the known apicoplast-targeted genes as well as many hypothetical genes. For reference, the average expression profile for the plastid genome is shown (dashed gray line).</p>\n <p>(B) Proteases represent an attractive target for chemotherapeutic development. The broad range of temporal expression for various classes of proteases and their putative functions are displayed.</p>\n <p>Abbreviations: HAP, histo-aspartyl protease (PM III); Clp, caseineolytic protease; sub1, 2, subtilisin-like protease 1 and 2.</p></div>", "links"=>[], "tags"=>["apicoplast-targeted", "proteins", "antimalarial"], "article_id"=>634725, "categories"=>["Microbiology", "Genetics", "Infectious Diseases"], "users"=>["Zbynek Bozdech", "Manuel Llinás", "Brian Lee Pulliam", "Edith D Wong", "Jingchun Zhu", "Joseph L DeRisi"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.0000005.g004", "stats"=>{"downloads"=>2, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Temporal_Distribution_of_the_Apicoplast_Targeted_Proteins_and_P_falciparum_Proteases_Potential_Antimalarial_Drug_Candidates_/634725", "title"=>"Temporal Distribution of the Apicoplast-Targeted Proteins and P. falciparum Proteases, Potential Antimalarial Drug Candidates", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 09:22:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/474132", "https://ndownloader.figshare.com/files/474134", "https://ndownloader.figshare.com/files/474135", "https://ndownloader.figshare.com/files/474136", "https://ndownloader.figshare.com/files/474138", "https://ndownloader.figshare.com/files/474141", "https://ndownloader.figshare.com/files/474257", "https://ndownloader.figshare.com/files/474258", "https://ndownloader.figshare.com/files/474259", "https://ndownloader.figshare.com/files/474260", "https://ndownloader.figshare.com/files/474261", "https://ndownloader.figshare.com/files/474262", "https://ndownloader.figshare.com/files/474263", "https://ndownloader.figshare.com/files/474264", "https://ndownloader.figshare.com/files/474265", "https://ndownloader.figshare.com/files/474266", "https://ndownloader.figshare.com/files/474267", "https://ndownloader.figshare.com/files/474268", "https://ndownloader.figshare.com/files/474269", "https://ndownloader.figshare.com/files/474270", "https://ndownloader.figshare.com/files/474271", "https://ndownloader.figshare.com/files/474272", "https://ndownloader.figshare.com/files/474273", "https://ndownloader.figshare.com/files/474274", "https://ndownloader.figshare.com/files/474275", "https://ndownloader.figshare.com/files/474276", "https://ndownloader.figshare.com/files/474277", "https://ndownloader.figshare.com/files/474278", "https://ndownloader.figshare.com/files/474279"], "description"=>"<div><p>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 <em>Plasmodium</em>-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.</p> </div>", "links"=>[], "tags"=>["transcriptome", "intraerythrocytic"], "article_id"=>153399, "categories"=>["Cancer", "Genetics", "Microbiology"], "users"=>["Zbynek Bozdech", "Manuel Llinás", "Brian Lee Pulliam", "Edith D Wong", "Jingchun Zhu", "Joseph L DeRisi"], "doi"=>["https://dx.doi.org/10.1371/journal.pbio.0000005.sd001", "https://dx.doi.org/10.1371/journal.pbio.0000005.sd002", "https://dx.doi.org/10.1371/journal.pbio.0000005.sd003", "https://dx.doi.org/10.1371/journal.pbio.0000005.sd004", "https://dx.doi.org/10.1371/journal.pbio.0000005.sg001", "https://dx.doi.org/10.1371/journal.pbio.0000005.sg002", "https://dx.doi.org/10.1371/journal.pbio.0000005.sg003", "https://dx.doi.org/10.1371/journal.pbio.0000005.sg004", "https://dx.doi.org/10.1371/journal.pbio.0000005.sg005", "https://dx.doi.org/10.1371/journal.pbio.0000005.sg006", "https://dx.doi.org/10.1371/journal.pbio.0000005.sg007", "https://dx.doi.org/10.1371/journal.pbio.0000005.sg008", "https://dx.doi.org/10.1371/journal.pbio.0000005.sg009", "https://dx.doi.org/10.1371/journal.pbio.0000005.sg010", "https://dx.doi.org/10.1371/journal.pbio.0000005.sg011", "https://dx.doi.org/10.1371/journal.pbio.0000005.sg012", "https://dx.doi.org/10.1371/journal.pbio.0000005.sg013", "https://dx.doi.org/10.1371/journal.pbio.0000005.sg014", "https://dx.doi.org/10.1371/journal.pbio.0000005.sg015", "https://dx.doi.org/10.1371/journal.pbio.0000005.sg016", "https://dx.doi.org/10.1371/journal.pbio.0000005.sg017", "https://dx.doi.org/10.1371/journal.pbio.0000005.sg018", "https://dx.doi.org/10.1371/journal.pbio.0000005.st001", "https://dx.doi.org/10.1371/journal.pbio.0000005.st002", "https://dx.doi.org/10.1371/journal.pbio.0000005.st003", "https://dx.doi.org/10.1371/journal.pbio.0000005.st004", "https://dx.doi.org/10.1371/journal.pbio.0000005.st005", "https://dx.doi.org/10.1371/journal.pbio.0000005.st006", "https://dx.doi.org/10.1371/journal.pbio.0000005.st007"], "stats"=>{"downloads"=>58, "page_views"=>82, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/The_Transcriptome_of_the_Intraerythrocytic_Developmental_Cycle_of_Plasmodium_falciparum_/153399", "title"=>"The Transcriptome of the Intraerythrocytic Developmental Cycle of Plasmodium falciparum", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-01-20 11:45:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/964834"], "description"=>"<p>The similarity of all expression profiles to seven known vaccine candidates (boxed) was calculated. The top 5% of similar profiles correspond to 262 ORFs, 28 of which have been previously associated with plasmodial antigenicity and the process of merozoite invasion.</p>", "links"=>[], "tags"=>["putative"], "article_id"=>634762, "categories"=>["Microbiology", "Genetics", "Infectious Diseases"], "users"=>["Zbynek Bozdech", "Manuel Llinás", "Brian Lee Pulliam", "Edith D Wong", "Jingchun Zhu", "Joseph L DeRisi"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.0000005.g005", "stats"=>{"downloads"=>1, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Phaseogram_of_Putative_Vaccine_Targets_/634762", "title"=>"Phaseogram of Putative Vaccine Targets", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 09:23:48"}

PMC Usage Stats | Further Information

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