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Open Access Highly Accessed Research article

Origin and evolution of the Notch signalling pathway: an overview from eukaryotic genomes

Eve Gazave1, Pascal Lapébie1, Gemma S Richards2, Frédéric Brunet3, Alexander V Ereskovsky14, Bernard M Degnan2, Carole Borchiellini1, Michel Vervoort56 and Emmanuelle Renard1*

Author Affiliations

1 Aix-Marseille Universités, Centre d'Océanologie de Marseille, Station marine d'Endoume - CNRS UMR 6540-DIMAR, rue de la Batterie des Lions, 13007 Marseille, France

2 School of Biological Sciences, University of Queensland, Brisbane, QLD 4072, Australia

3 Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, CNRS UMR 5242, INRA, IFR128 BioSciences Lyon-Gerland, Ecole Normale Supérieure de Lyon, 46, Allée d'Italie, 69007 Lyon, France

4 Department of Embryology, Faculty of Biology and Soils, Saint-Petersburg State University, Universitetskaja nab. 7/9, St Petersburg, Russia

5 Institut Jacques Monod, UMR 7592 CNRS/Université Paris Diderot - Paris 7, 15 rue Hélène Brion, 75205 Paris Cedex 13, France

6 UFR de Biologie et Sciences de la Nature, Université Paris 7 - Denis Diderot, 2 place Jussieu, 75251 Paris Cedex 05, France

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BMC Evolutionary Biology 2009, 9:249  doi:10.1186/1471-2148-9-249

Published: 13 October 2009



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.


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.


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.