Origin and evolution of the Notch signalling pathway: an overview from eukaryotic genomes.
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.
Gazave
Eve
E
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
Lapébie
Pascal
P
Richards
Gemma S
GS
Brunet
Frédéric
F
Ereskovsky
Alexander V
AV
Degnan
Bernard M
BM
Borchiellini
Carole
C
Vervoort
Michel
M
Renard
Emmanuelle
E
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
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