A Phylogenetic Analysis of Vertebrate and Invertebrate Notch-Related Genes

Members of the Notch gene family are thought to mediate inductive cell-cell interactions during develop ment of a wide variety of vertebrates and invertebrates. These genes encode transmembrane proteins that appear to act as receptors and contain three repeated sequence motifs. Two of these motifs (an epidermal growth factor like sequence and a cdc10/SW16/ankyrin sequence) have been found in a large number of unrelated proteins, while the third motif (a lin-12/Notch/glp-1 sequence) is unique to proteins of the Notch family. We present a phylogenetic analysis of 17 Notch-related genes from eight species that has implications as to the origins and relative functions of these genes in different species. Several independent gene duplications have occurred and at least one such duplication in the vertebrate lineage preceded the avian/mammalian divergence. Significantly, the overall organization of individual members of each internally repeated motif ap pears to have been conserved among species, suggesting that each repeat plays a unique role in protein function. Yet, where sequence divergence does occur among genes in vertebrate, dipteran, and nematode lineages, it may signify functional differences for specific regions in Notch-related proteins.