THE DROSOPHILA-MELANOGASTER DODO (DOD) GENE, CONSERVED IN HUMANS, IS FUNCTIONALLY INTERCHANGEABLE WITH THE ESS1 CELL-DIVISION GENE OF SACCHAROMYCES-CEREVISIAE

We have sequenced the region of DNA adjacent to and including the flig htless (fli) gene of Drosophila melanogaster and molecularly character ized four transcription units within it, which we have named tweety (t we), flightless (fli), dodo (dod), and penguin (pen). We have performe d deletion and transgenic analysis to determine the consequences of th e quadruple gene removal, Only the flightless gene is vital to the org anism; the simultaneous absence of the other three allows the overridi ng majority of individuals to develop to adulthood and to fly normally . These gene deletion results are evaluated in the context of the redu ndancy and degeneracy inherent in many genetic networks, Our cDNA anal yses and data-base searches reveal that the predicted dodo protein has homologs in other eukaryotes and that it is made up of two different domains, The first, designated WW, is involved in protein-protein inte ractions and is found in functionally diverse proteins including human dystrophin, The second is involved in accelerating protein folding an d unfolding and is found in Escherichia coli in a new family of peptid ylprolyl cis-trans isomerases (PPIases; EC 5.2.1.8), In eukaryotes, PP Iases occur in the nucleus and the cytoplasm and can form stable assoc iations with transcription factors, receptors, and kinases, Given this particular combination of domains, the dodo protein may well particip ate in a multisubunit complex involved in the folding and activation o f signaling molecules, When we expressed the dodo gene product in Sacc haromyces cerevisiae, it rescued the lethal phenotype of the ESS1 cell division gene.