Comparative genomics of transcriptional control in the human malaria parasite Plasmodium falciparum.

The life cycle of the parasite Plasmodium falciparum, responsible for the most deadly form of human malaria, requires specialized protein expression for survival in the mammalian host and insect vector. To identify components of processes controlling gene expression during its life cycle, the malarial genome--along with seven crown eukaryote group genomes--was queried with a reference set of transcription-associated proteins (TAPs). Following clustering on the basis of sequence similarity of the TAPs with their homologs, and together with hidden Markov model profile searches, 156 P. falciparum TAPs were identified. This represents about a third of the number of TAPs usually found in the genome of a free-living eukaryote. Furthermore, the P. falciparum genome appears to contain a low number of sequences, which are highly conserved and abundant within the kingdoms of free-living eukaryotes, that contribute to gene-specific transcriptional regulation. However, in comparison with these other eukaryotic genomes, the CCCH-type zinc finger (common in proteins modulating mRNA decay and translation rates) was found to be the most abundant in the P. falciparum genome. This observation, together with the paucity of malarial transcriptional regulators identified, suggests Plasmodium protein levels are primarily determined by posttranscriptional mechanisms.

[1]  E. Birney,et al.  Pfam: the protein families database , 2013, Nucleic Acids Res..

[2]  R. Tjian,et al.  Transcription regulation and animal diversity , 2003, Nature.

[3]  L. Bannister,et al.  The ins, outs and roundabouts of malaria. , 2003, Trends in parasitology.

[4]  K. Natarajan,et al.  A Multiplicity of Coactivators Is Required by Gcn4p at Individual Promoters In Vivo , 2003, Molecular and Cellular Biology.

[5]  Sophia Tsoka,et al.  The phylogenetic extent of metabolic enzymes and pathways. , 2003, Genome research.

[6]  Christos A Ouzounis,et al.  The phylogenetic diversity of eukaryotic transcription. , 2003, Nucleic acids research.

[7]  Jian Wang,et al.  The Genome Sequence of the Malaria Mosquito Anopheles gambiae , 2002, Science.

[8]  Peer Bork,et al.  Comparative Genome and Proteome Analysis of Anopheles gambiae and Drosophila melanogaster , 2002, Science.

[9]  Jonathan E. Allen,et al.  Genome sequence of the human malaria parasite Plasmodium falciparum , 2002, Nature.

[10]  R. Gwilliam,et al.  Sequence of Plasmodium falciparum chromosomes 1, 3–9 and 13 , 2002, Nature.

[11]  David L. Tabb,et al.  A proteomic view of the Plasmodium falciparum life cycle , 2002, Nature.

[12]  Neil Hall,et al.  Analysis of the Plasmodium falciparum proteome by high-accuracy mass spectrometry , 2002, Nature.

[13]  Tomoaki Tamaki,et al.  Sequence of Plasmodium falciparum chromosome 12 , 2002, Nature.

[14]  J. Schug,et al.  The Plasmodium genome database , 2002, Nature.

[15]  C. Newbold,et al.  Stage-specific promoter activity from stably maintained episomes in Plasmodium falciparum. , 2002, International journal for parasitology.

[16]  C. Clayton,et al.  Life without transcriptional control? From fly to man and back again , 2002, The EMBO journal.

[17]  T. Maniatis,et al.  An extensive network of coupling among gene expression machines , 2002, Nature.

[18]  Anton J. Enright,et al.  An efficient algorithm for large-scale detection of protein families. , 2002, Nucleic acids research.

[19]  P. Blackshear,et al.  Interactions of CCCH Zinc Finger Proteins with mRNA , 2002, The Journal of Biological Chemistry.

[20]  R. Kingston,et al.  Cooperation between Complexes that Regulate Chromatin Structure and Transcription , 2002, Cell.

[21]  B. Barrell,et al.  The genome sequence of Schizosaccharomyces pombe , 2002, Nature.

[22]  A. Holder,et al.  Stage-Specific Transcription of Distinct Repertoires of a Multigene Family During Plasmodium Life Cycle , 2002, Science.

[23]  T. Wellems,et al.  Malaria: Cooperative silencing elements in var genes , 2001, Nature.

[24]  C. Allis,et al.  Translating the Histone Code , 2001, Science.

[25]  R. Parker,et al.  The Transcription Factor Associated Ccr4 and Caf1 Proteins Are Components of the Major Cytoplasmic mRNA Deadenylase in Saccharomyces cerevisiae , 2001, Cell.

[26]  F. Winston Control of eukaryotic transcription elongation , 2001, Genome Biology.

[27]  R. R. Samaha,et al.  Arabidopsis transcription factors: genome-wide comparative analysis among eukaryotes. , 2000, Science.

[28]  The Arabidopsis Genome Initiative Analysis of the genome sequence of the flowering plant Arabidopsis thaliana , 2000, Nature.

[29]  Chris Sander,et al.  CAST: an iterative algorithm for the complexity analysis of sequence tracts , 2000, Bioinform..

[30]  D. Wassarman,et al.  Genes Encoding Drosophila melanogaster RNA Polymerase II General Transcription Factors , 2000, The Journal of cell biology.

[31]  P. Blackshear,et al.  Interactions of CCCH Zinc Finger Proteins with mRNA , 2000, The Journal of Biological Chemistry.

[32]  M. Ashburner,et al.  Gene Ontology: tool for the unification of biology , 2000, Nature Genetics.

[33]  Stephen M. Mount,et al.  The genome sequence of Drosophila melanogaster. , 2000, Science.

[34]  M. Green,et al.  TBP-associated factors (TAFIIs): multiple, selective transcriptional mediators in common complexes. , 2000, Trends in biochemical sciences.

[35]  C. Denis,et al.  The CCR4 and CAF1 Proteins of the CCR4-NOT Complex Are Physically and Functionally Separated from NOT2, NOT4, and NOT5 , 1999, Molecular and Cellular Biology.

[36]  K. Struhl Fundamentally Different Logic of Gene Regulation in Eukaryotes and Prokaryotes , 1999, Cell.

[37]  Koen J. Dechering,et al.  Isolation and Functional Characterization of Two Distinct Sexual-Stage-Specific Promoters of the Human Malaria Parasite Plasmodium falciparum , 1999, Molecular and Cellular Biology.

[38]  A. Scherf,et al.  Antigenic variation in malaria: in situ switching, relaxed and mutually exclusive transcription of var genes during intra‐erythrocytic development in Plasmodium falciparum , 1998, The EMBO journal.

[39]  M Lanzer,et al.  Control of gene expression in Plasmodium falciparum. , 1998, Molecular and biochemical parasitology.

[40]  K. Struhl,et al.  Targeted Recruitment of the Sin3-Rpd3 Histone Deacetylase Complex Generates a Highly Localized Domain of Repressed Chromatin In Vivo , 1998, Molecular and Cellular Biology.

[41]  S. Harashima,et al.  Yeast Coactivator MBF1 Mediates GCN4-Dependent Transcriptional Activation , 1998, Molecular and Cellular Biology.

[42]  S. Elledge,et al.  Human Cyclin K, a Novel RNA Polymerase II-Associated Cyclin Possessing Both Carboxy-Terminal Domain Kinase and Cdk-Activating Kinase Activity , 1998, Molecular and Cellular Biology.

[43]  B. Crombrugghe,et al.  Role of the CCAAT-binding protein CBF/NF-Y in transcription. , 1998, Trends in biochemical sciences.

[44]  Thomas L. Madden,et al.  Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. , 1997, Nucleic acids research.

[45]  D. Arnot,et al.  A Plasmodium falciparum homologue of the ATPase subunit of a multi-protein complex involved in chromatin remodelling for transcription. , 1997, Molecular and biochemical parasitology.

[46]  R Ohba,et al.  Yeast Gcn5 functions in two multisubunit complexes to acetylate nucleosomal histones: characterization of an Ada complex and the SAGA (Spt/Ada) complex. , 1997, Genes & development.

[47]  B. Barrell,et al.  Life with 6000 Genes , 1996, Science.

[48]  Thure Etzold,et al.  SRS - an indexing and retrieval tool for flat file data libraries , 1993, Comput. Appl. Biosci..

[49]  D. Mccormick Sequence the Human Genome , 1986, Bio/Technology.

[50]  Anton J. Enright,et al.  Transcription-associated protein families are primarily taxon-specific , 2001, Bioinform..

[51]  International Human Genome Sequencing Consortium Initial sequencing and analysis of the human genome , 2001, Nature.

[52]  Rolf Apweiler,et al.  The SWISS-PROT protein sequence database and its supplement TrEMBL in 2000 , 2000, Nucleic Acids Res..

[53]  Sean R. Eddy,et al.  Profile hidden Markov models , 1998, Bioinform..

[54]  J. Berg Genome sequence of the nematode C. elegans: a platform for investigating biology. , 1998, Science.

[55]  S. Bell,et al.  Transcription in Archaea. , 1998, Cold Spring Harbor symposia on quantitative biology.

[56]  Holger Karas,et al.  TRANSFAC: a database on transcription factors and their DNA binding sites , 1996, Nucleic Acids Res..

[57]  A. Waters The ribosomal RNA genes of Plasmodium. , 1994, Advances in parasitology.