A complex genetic locus that controls the first three steps of pyrimidine biosynthesis in Drosophila

Abstract

IN eukaryotes, the initial steps in the de novo synthesis of pyrimidines are performed by multienzyme complexes consisting of the first two enzymes in fungi and the first three enzymes in mammals^1,2. In Neurospora there is evidence that this complex facilitates channelling of the carbamyl phosphate produced by pyrimidine-specific carbamyl phosphate synthetase (CPSase) to the second enzyme, aspartate transcarbamylase (ATCase)³. The aggregation of these enzymes in fungi correlates with close linkage of the structural genes for both CPSase and ATCase which are apparently cotranscribed and translated^4–7. In fungi the third pyrimidine pathway enzyme, dihydroorotase (DHOase) is encoded by an unlinked gene^5,8. Considering the close relationship between enzyme aggregation and gene clustering in this system in fungi, the presence of the first three steps of pyrimidine biosynthesis in a single mammalian enzyme aggregate led us to question whether all three structural genes may be clustered in animals. We now report that this is the case in Drosophila and that the fourth enzyme in the pathway is not included within this gene cluster.