Evolutionary analysis of vertebrate Notch genes

We have conducted an evolutionary analysis of Notch genes of the vertebrate s Danio rerio and Mus musculus to examine the expansion and diversification of the Notch family during vertebrate evolution. The existence of multiple Notch genes in vertebrate genomes suggests that the increase in Notch sign aling pathways may be necessary for the additional complexity observed in t he vertebrate body plan. However, orthology relationships within the verteb rate Notch family indicate that biological functions are not fixed within o rthologous groups. Phylogenetic reconstruction of the vertebrate Notch fami ly suggests that the zebrafish notch1a and 1b genes resulted from a duplica tion occurring around the time of the teleost/mammalian divergence. There i s also evidence that the mouse Notch4 gene is the result of a rapid diverge nce from a Notch3-like gene. Investigation of the ankyrin repeat region seq uences showed there to belittle evidence for gene conversion events between repeat units. However; relationships between repeats 2-5 suggest that thes e repeats, are the result of a tandem duplication of a dual repeat unit. Se lective pressure on maintenance of ankyrin repeat sequences indicated by re lationships between the repeats suggests that specific repeats are responsi ble for particular biological activities, a finding consistent with mutatio nal studies of the Caenorhabditis elegans gene glp-1. Sequence similarities between the ankyrin repeats and the region immediately C-terminal of the r epeats further suggests that this region may be involved in the modulation of ankyrin repeat function.