title: Origin and evolution of the Notch signalling pathway: an overview from eukaryotic genomes.
abstract: BACKGROUND
  Of the 20 or so signal transduction pathways that orchestrate cell-cell interactions in metazoans, seven are involved during development. One of these is the Notch signalling pathway which regulates cellular identity, proliferation, differentiation and apoptosis via the developmental processes of lateral inhibition and boundary induction. In light of this essential role played in metazoan development, we surveyed a wide range of eukaryotic genomes to determine the origin and evolution of the components and auxiliary factors that compose and modulate this pathway.
  
  
  RESULTS
  We searched for 22 components of the Notch pathway in 35 different species that represent 8 major clades of eukaryotes, performed phylogenetic analyses and compared the domain compositions of the two fundamental molecules: the receptor Notch and its ligands Delta/Jagged. We confirm that a Notch pathway, with true receptors and ligands is specific to the Metazoa. This study also sheds light on the deep ancestry of a number of genes involved in this pathway, while other members are revealed to have a more recent origin. The origin of several components can be accounted for by the shuffling of pre-existing protein domains, or via lateral gene transfer. In addition, certain domains have appeared de novo more recently, and can be considered metazoan synapomorphies.
  
  
  CONCLUSIONS
  The Notch signalling pathway emerged in Metazoa via a diversity of molecular mechanisms, incorporating both novel and ancient protein domains during eukaryote evolution. Thus, a functional Notch signalling pathway was probably present in Urmetazoa.
authors.affiliation: Aix-Marseille Universités, Centre d'Océanologie de Marseille, Station marine d'Endoume - CNRS UMR 6540-DIMAR, rue de Batterie des Lions, 13007 Marseille, France. eve.gazave@univmed.fr
authors.forename: Eve
authors.initials: E
authors.lastname: Gazave
authors.forename: Pascal
authors.initials: P
authors.lastname: Lapébie
authors.forename: Gemma S
authors.initials: GS
authors.lastname: Richards
authors.forename: Frédéric
authors.initials: F
authors.lastname: Brunet
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Ereskovsky
authors.forename: Bernard M
authors.initials: BM
authors.lastname: Degnan
authors.forename: Carole
authors.initials: C
authors.lastname: Borchiellini
authors.forename: Michel
authors.initials: M
authors.lastname: Vervoort
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Renard
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics; D005057:Eukaryotic Cells; D019143:Evolution, Molecular; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics; D010802:Phylogeny; D054730:Protein Interaction Domains and Motifs; D051880:Receptors, Notch / Q000235:genetics*; D017422:Sequence Analysis, DNA; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000235:genetics
chemical_list: D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; C064045:delta protein