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 flightless (fli) gene of Drosophila melanogaster and molecularly characterized four transcription units within it, which we have named tweety (twe), flightless (fli), dodo (dod), and penguin (pen). We have performed deletion and transgenic analysis to determine the consequences of the quadruple gene removal. Only the flightless gene is vital to the organism; the simultaneous absence of the other three allows the overriding majority of individuals to develop to adulthood and to fly normally. These gene deletion results are evaluated in the context of the redundancy and degeneracy inherent in many genetic networks. Our cDNA analyses 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 interactions and is found in functionally diverse proteins including human dystrophin. The second is involved in accelerating protein folding and unfolding and is found in Escherichia coli in a new family of peptidylprolyl cis-trans isomerases (PPIases; EC 5.2.1.8). In eukaryotes, PPIases occur in the nucleus and the cytoplasm and can form stable associations with transcription factors, receptors, and kinases. Given this particular combination of domains, the dodo protein may well participate in a multisubunit complex involved in the folding and activation of signaling molecules. When we expressed the dodo gene product in Saccharomyces cerevisiae, it rescued the lethal phenotype of the ESS1 cell division gene.
Maleszka
R
R
Visual Sciences Group, Research School of Biological Sciences, Australian National University, Canberra, Australia.
Hanes
S D
SD
Hackett
R L
RL
de Couet
H G
HG
Miklos
G L
GL
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D002455:Cell Division; D018076:DNA, Complementary / Q000235:genetics; D029721:Drosophila Proteins; D004331:Drosophila melanogaster; D005656:Fungal Proteins / Q000235:genetics*; D005800:Genes, Fungal; D017344:Genes, Insect; D005804:Genes, Lethal; D005816:Genetic Complementation Test; D006801:Humans; D008969:Molecular Sequence Data; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase; D011506:Proteins / Q000235:genetics*; D015183:Restriction Mapping; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; D029721:Drosophila Proteins; D005656:Fungal Proteins; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins; C000606845:ESS1 protein, S cerevisiae; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; C000606849:dod protein, Drosophila