THE MOLECULAR ANALYSIS OF THE ACE GENE IN DROSOPHILA

The rapid hydrolysis of the neurotransmitter, acetylcholine, is mediated by the enzyme acetylcholinesterase (AChE). This function is believed to be critical for the normal function of cholinergic neurotransmission. In Drosophila, AChE expression in nervous tissue is necessary for viability, behavior, and proper development of the nervous system. Genetic mosaic flies which are homozygous Ace('-) for portions of their nervous system can display abnormal behavior as well as morphological defects in their nervous tissue. AChE inactivation at specific times in the life cycle often result in death or behavioral abnormalities. The multimeric AChE enzyme is polymorphic in situ, having both soluble and hydrophobic forms. Evidence for 4-5 different catalytic subunits exists, some of these forms are specifically inactivated by Ace lethals in an allele specific manner.

The likely structural gene for AChE, Ace, is a large gene with a complex transcriptional pattern. By deletion mapping, Ace lies between +17 - +59 and is at least 16 kb in size. Recombinational analysis of cytologically normal Ace('-) alleles have identified sequences essential for Ace('+) expression. These regions have homology to four transcripts, three of which have a size and developmental profile consistent with the properties of AChE. The transcripts appear to be differentially spliced, with the putative exons possibly extending over as much as 20 kb. The organization of transcriptional activity in the Ace region and its relationship to AChE expression and structure is considered. Exceptional Ace('-) mutants recovered from the recombinational mapping experiments are also discussed.