Evolutionary scenarios of Notch proteins.

Notch is a highly conserved family of transmembrane receptors and transcription factors that are key players in several developmental processes. In this study, we identified novel Notch sequences from various species covering from worm to human and conducted a comprehensive phylogenetic analysis in order to confirm and extend the evolutionary history of Notch. Our findings confirm an independent duplication event in Caenorhabditis elegans resulting in two Notch genes and show that the vertebrate Notch genes resulted from two duplication events, both of which occurred before the divergence of teleosts and tetrapoda. Furthermore, we demonstrate that the vertebrate Notch2 group is phylogenetically closer to Notch3 and that Notch2 appeared at the first round of vertebrate duplication events. Moreover, there is evidence that the two Notch1 genes in fish, appeared by a recent duplication of Notch1 in teleost after the divergence of teleost and tetrapoda. Whether this is from ancient whole genome duplication (WGD) or gene duplication remains to be elucidated. The fourth group of Notch (Notch4) was found only in mammals. We suggest two possible scenarios for the origin of the Notch4 subfamily: 1) Notch4 appeared at the time of the two WGDs in the early chordate but has been maintained only in the mammalian lineage and was lost in the other lineages, 2) a recent independent duplication event took place in the mammalian lineage. The increase of the sequencing data from Xenopus tropicalis, Gallus gallus genome projects and of other avian and reptile genomes will shed more light on this event. Nevertheless, the great divergence of Notch4, from the other three Notch genes, suggests a rapid divergence raising questions about the functional implication of this event. In addition, comparison of the organization of Notch syntenic genes among species supports the coordinated rearrangements during evolution for Ntch, PBX, and BRD families that may lead to possible functional relationships.