title: The dominant mutation Suppressor of black indicates that de novo pyrimidine biosynthesis is involved in the Drosophila tan pigmentation pathway.
abstract: A deficiency in the production of beta-alanine causes the black (b) phenotype of Drosophila melanogaster. This phenotype is normalized by a semi-dominant mutant gene Su(b) shown previously to be located adjacent to or within the rudimentary (r) locus. The r gene codes for three enzyme activities involved in de novo pyrimidine biosynthesis. Pyrimidines are known to give rise to beta-alanine. However, until recently it has been unclear whether de novo pyrimidine biosynthesis is directly coupled to beta-alanine synthesis during the tanning process. In this report we show that flies carrying Su(b) can exhibit an additional phenotype, resistance to toxic pyrimidine analogs (5-fluorouracil, 6-azathymine and 6-azauracil). Our interpretation of this observation is that the pyrimidine pool is elevated in the mutant flies. However, enzyme assays indicate that r enzyme activities are not increased in Su(b) flies. Genetic mapping of the Su(b) gene now places the mutation within the r gene, possibly in the carbamyl phosphate synthetase (CPSase) domain. The kinetics of CPSase activity in crude extracts has been studied in the presence of uridine triphosphate (UTP). While CPSase from wild-type flies was strongly inhibited by the end-product, UTP, CPSase from Su(b) was inhibited to a lesser extent. We propose that diminished end-product inhibition of de novo pyrimidine biosynthesis in Su(b) flies increases available pyrimidine and consequently the beta-alanine pool. Normalization of the black phenotype results.
authors.affiliation: Department of Genetics, University of Copenhagen, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Piskur
authors.forename: D
authors.initials: D
authors.lastname: Kolbak
authors.forename: L
authors.initials: L
authors.lastname: Søndergaard
authors.forename: M B
authors.initials: MB
authors.lastname: Pedersen
mesh_terms: D000818:Animals; D001221:Aspartate Carbamoyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / Q000235:genetics / Q000378:metabolism; D003116:Color; D004080:Dihydroorotase / Q000235:genetics / Q000378:metabolism; D004330:Drosophila; D005260:Female; D005799:Genes, Dominant; D008297:Male; D010641:Phenotype; D011743:Pyrimidines / Q000096:biosynthesis* / Q000494:pharmacology; D013489:Suppression, Genetic; D015091:beta-Alanine / Q000235:genetics*
chemical_list: D011743:Pyrimidines; D015091:beta-Alanine; D001221:Aspartate Carbamoyltransferase; D004080:Dihydroorotase; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing)