Selected genes in Drosophila melanogaster are being studied in an effort to understand their organization and regulation through the analysis of mutations that upset regulatory functions. A locus of particular interest is white, which controls one of the steps in the pigmentation of the eyes, Malpighlian tubules and testis sheath in Drosophila. The molecular analysis of mutants shows that a large proportion of spontaneous changes result from the insertion/deletion of transposable elements. We are studying mutations that cause mosaic expressions of the white locus. The original mutations of this series resulted from the insertion of the transposon Bel into the large intron of white. This mutant, wzm, produces a mottle-eye phenotype only when combined with a mutation at the zeste locus, z1, otherwise it has a wild-type phenotype. Wzm is mildly unstable and has produced a series of other alleles including a transposition of an X chromosome segment containing white into the third chromosome. In the new position, the white locus produces a wild-type phenotype except when the transposition is homozygous and the z1 mutation is present. That genotype produces a mosaic eye-color that is nonautonomous and nonclonal in expression, marking a dramatic change from the autonomous, clonal patterns seen in the non- transposed wzm and its derivatives. The molecular analyses of these mutant alleles are being done to determine the basis for the modified expression of white and its interaction with zeste. Another aspect of the zeste-white interaction is a transvection effect that is dependent on the relative positions in the genome that the two white genes occupy. Two w+ genes close together (as in paired homologs or a tandem duplication) are suppressed by z1, but if separated by chromosomal rearrangements, z1 has not effect. We are examining the basis for this effect of chromatin architecture on gene regulation.
