Recent findings in Drosophila have shown that 1) a significant proportion of spontaneous mutations are caused by insertions of mobile genetic elements, and 2) in certain genetic suppressor systems, suppressible alleles are caused by insertions of specific mobile elements. We are investigating the molecular mechanism of action of one such suppressor system: recessive mutations at the suppressor-of-sable (su(s)) locus suppress recessive mutations at the vermilion (v) locus that are caused by insertions of the mobile elements 412. Current results suggest that this suppression occurs pretranslationally. DNA sequences of su(s) have been cloned and are being characterized structurally and functionally. An 8 kb segment of genomic DNA that gives rise to a 5 kb polyA+ message has been sequenced. It contains three open reading frames that range in size from 700 to 1800 bases. cDNA clones have not yet been recovered, so the precise splicing pattern remains unknown. A """"""""conceptual"""""""" protein produced by the 3 ORFs has no homology with any protein in the protein data bases. Portions of the cloned 25 kb of DNA have been reintroduced by P element mediated transformation and allow an identification of genetic function with messages produced by the region. A segment of DNA which is homologous with only the su(s) message rescues both the primary phenotype of suppression and a secondary phenotype of cold-sensitive male sterility. Antibodies raised against fusion proteins produced by portions of the above ORFs specifically recognize the s(s) portion of the fusion protein, but fail to detect any proteins in extracts from Drosophila embryos or adults.
