An Orthologics Study of the Notch Signalling Pathway

The Notch signaling pathway plays a major role in embryological development and in the ongoing life processes of many animals. Its role is to provide cell-to-cell communication in which a Sender cell, bearing membrane -embedded ligands, instructs a Receiver cell, bearing membrane- embedded receptors, to adopt one of two available fates. Elucidating the evolution of this pathway is the topic of this paper, which uses an orthologs approach to build a firm base for such a study. Using BLAST searches, orthologs were identified for all of the 49 listed components of the Notch signaling pathway. The time course of the integration of these proteins as animal evolution proceeded was elucidated. Insofar as cell –to-cell communication is only of relevance in multicellular animals, it is not surprising that the Notch system reached a fully-working configuration only with the evolutionary appearance of the Metazoa, the first multicellular animals The roles of the Notch system’s 49 components in contemporary descendants of the ortholog-contributing ancestors were ascertained from a survey of the literature. A single protein, the protein tyrosine kinase (PTK) of the protozoan Ministeria vibrans was identified as a possible pre-Metazoan ancestor of the DLL, JAG, and NOTCH proteins. A scenario for the evolution of the Notch signaling pathway is presented and described as the co-option of its components, clade by clade, in a repurposing of genes already present in the ancestral unicellular organisms.