title: The Evolution of COP9 Signalosome in Unicellular and Multicellular Organisms.
abstract: The COP9 signalosome (CSN) is a highly conserved protein complex, recently being crystallized for human. In mammals and plants the COP9 complex consists of nine subunits, CSN 1-8 and CSNAP. The CSN regulates the activity of culling ring E3 ubiquitin and plays central roles in pleiotropy, cell cycle, and defense of pathogens. Despite the interesting and essential functions, a thorough analysis of the CSN subunits in evolutionary comparative perspective is missing. Here we compared 61 eukaryotic genomes including plants, animals, and yeasts genomes and show that the most conserved subunits of eukaryotes among the nine subunits are CSN2 and CSN5. This may indicate a strong evolutionary selection for these two subunits. Despite the strong conservation of the protein sequence, the genomic structures of the intron/exon boundaries indicate no conservation at genomic level. This suggests that the gene structure is exposed to a much less selection compared with the protein sequence. We also show the conservation of important active domains, such as PCI (proteasome lid-CSN-initiation factor) and MPN (MPR1/PAD1 amino-terminal). We identified novel exons and alternative splicing variants for all CSN subunits. This indicates another level of complexity of the CSN. Notably, most COP9-subunits were identified in all multicellular and unicellular eukaryotic organisms analyzed, but not in prokaryotes or archaeas. Thus, genes encoding CSN subunits present in all analyzed eukaryotes indicate the invention of the signalosome at the root of eukaryotes. The identification of alternative splice variants indicates possible "mini-complexes" or COP9 complexes with independent subunits containing potentially novel and not yet identified functions.
authors.affiliation: Bioinformatics/High Throughput Analysis, Friedrich Schiller University, Jena, Germany FLI Leibniz Institute for Age Research, Jena, Germany.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Barth
authors.affiliation: Bioinformatics/High Throughput Analysis, Friedrich Schiller University, Jena, Germany Institute of Human Genetics, Jena University Hospital, Jena, Germany Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute (HKI), Jena, Germany.
authors.forename: Ron
authors.initials: R
authors.lastname: Hübler
authors.affiliation: Institute of Human Genetics, Jena University Hospital, Jena, Germany aria.baniahmad@med.uni-jena.de manja@uni-jena.de.
authors.forename: Aria
authors.initials: A
authors.lastname: Baniahmad
authors.affiliation: Bioinformatics/High Throughput Analysis, Friedrich Schiller University, Jena, Germany FLI Leibniz Institute for Age Research, Jena, Germany aria.baniahmad@med.uni-jena.de manja@uni-jena.de.
authors.forename: Manja
authors.initials: M
authors.lastname: Marz
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D000075686:COP9 Signalosome Complex; D019143:Evolution, Molecular; D005091:Exons; D006801:Humans; D007438:Introns; D046912:Multiprotein Complexes / Q000235:genetics*; D010447:Peptide Hydrolases / Q000235:genetics*; D010802:Phylogeny; D021122:Protein Subunits / Q000235:genetics
chemical_list: D046912:Multiprotein Complexes; D021122:Protein Subunits; D010447:Peptide Hydrolases; D000075686:COP9 Signalosome Complex
keywords: animal kingdom; bacteria; comparative informatics for plants; fungi; genomic structure; signalosome subunits CSN