Rapid divergence in the course of Drosophila evolution reveals structural important domains of the Notch antagonist Hairless

Hairless is a member of the Notch signalling pathway, where it acts as anta gonist by binding to Suppressor of Hairless [Su(H)], thereby inhibiting Not ch target gene activation. The pathway and its members are highly conserved in metazoans from worms to humans. However, a Hairless orthologue from ano ther species has not yet been identified. The identification of Hairless in largely diverged species by cross-hybridization has failed so far probably due to a low degree of conservation. Therefore, we turned to D, hydei wher e a Hairless mutation has been described before. The D. hydei Hairless orth ologue is reasonably well conserved with regard to gene structure and expre ssion. The prospective Hairless protein orthologues share several highly co nserved regions which are separated by quite diverged stretches. As to be e xpected, the largest region of high conservation corresponds to the Su(H) b inding domain. This region is also functionally conserved, since this D. hy dei protein domain binds very strongly to the D. melanogaster Su(H) protein . The other conserved regions support our earlier structure-function analys is since they nicely correspond to previously defined, functionally importa nt protein domains, Most notably, the very C-terminal domain which is very sensitive to structural alterations, is nearly identical between the two sp ecies. In summary, this evolutionary study improves the knowledge on functi onally significant domains of the Hairless protein, and may be helpful for the future identification of homologues in other animals, especially in ver tebrates.