We propose continuing the investigation of the Segregation distorter (SD) system which results in abnormal meiosis and/or spermatogenesis in Drosophila. The main elements of the SD system include the euchromatic allele Sd and the heterochromatic element E(SD), whose products interact to cause dysfunction of sperm containing a repetitive DNA sequence (Rsps) mapping to the 2 centromere. Transpositions, partial deletions and additions of Rsps DNA by P-element mediated transformation will be used to specify dose-response relationships between number of SD elements, Rsps repeat copy number, and level of sperm dysfunction, and to demonstrate directly the role of the DNA repeats in causing sperm dysfunction. These experiments will also lead to a cytogenetic characterization of 2R heterochromatin; in particular, a side product may be the use of chromosome rearrangements with breakpoints tagged by Rsps DNA repeats to identify centromeric DNA. We will use P-element mutagenesis to produce tagged mutations in E(SD), Sd or other as yet uncharacterized genes of the SD system, and we will use detachment of X^X chromosomes to yield Dp (2;X)E(SD) chromosomes, useful for measuring the dosage relationships between Sd and E(SD) in causing sperm dysfunction. These should allow detailed analysis of E(SD), the last major locus of the SD system so characterized. An understanding of genetic changes leading to errors in sperm development in Drosophila may provide clues for a better understanding of the normal fertility process in more complex eukaryotic organisms.***//
