The DNA sequences for two Drosophila loci have recently been isolated, and many mutant lesions have been mapped and characterized in both cases. The first locus, named rosy, codes for the enzyme xanthine dehydrogenase. The extensive genetic analysis of this locus has defined a protein coding region, flanked by an adjacent control region. Mutations in the control region are now being defined on the DNA sequence, and additional control mutants are being generated in-vitro, for transformation back into animals. The proposed experiments will map within the control region the starting point of the RNA transcript, and will determine if the initiation point or the RNA processing sites change with development. Nonsense mutants will also be constructed in the rosy coding sequence to make possible a search for nonsense suppressors in Drosophila. The second locus, called the bithorax complex, is a cluster of genes which control the differentiation of most of the segments of the fly; mutations cause transformation of one segment into another. The complex stretches over more than 300 kb of DNA. The right half of the complex, which controls development of the abdominal segments, is still being isolated and mapped. Future experiments will define RNA transcripts and splicing patterns in the right half of the complex. Attempts will be made concurrently to rescue mutants in the abdominal region by transformation with cloned DNA, so that the genetic analysis can be refined by directed in-vitro mutagenesis. Many of the spontaneous mutations in the bithorax complex are suppressed by a specific second site suppressor; these all have insertions of a particular mobile element. That element will be placed in and around a more simple gene to better analyze the mechanism of suppression.
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