The Ty elements of yeast are a family of highly related transposable present in the genomes of a variety of species. These elements elements are highly transcribed; transcriptional regulation occurs in response to cell mating type. The elements transpose to new locations by a process, similar to that of bacterial moveable elements, involving an illegitimate recombination event. The insertion creates a 5 bp duplication of DNA from the target site. Two mutations of the his4 region arose by such an insertion of Ty elements (Ty912 and Ty917 into the promoter region. These insertions eliminate normal transcription and put the expression of the gene under the control of unlinked loci (spm elements). His+ revertants of one mutation (his4-912) occur by a variety of Ty912-promoted chromosomal rearrangements including deletions, inversions, transpositions and translocations. These events are similar to those responsible for chromosomal rearrangements causing such human gentic diseases as "cri-du-chat" syndrome. We will investigate the mechanism of these yeast mutations using molecular cloning and DNA sequence analysis to determine if they result from recombination between existing elements or a process akin to transposition. The HLI+ deletions of Ty912 fuse the his4 gene to Ty genes. In these mutations the expression of his4 is directly under the control of the Ty element. We will use these gene fusions, and others created by in vitro mutagenesis, to study both the transcription of the Ty912 element and the regulation of that transcription. The Ty elements are an ideal model system with which to study the molecular evolution of repeated gene families. The sequences of individual elements evolve through both base substitution and large internal rearrangement of the element. Ty elements include flanking direct repeats (" regions"). Although regions have accumulated up to 20% sequence differences between elements, they remain identical within a given element. This fact suggests that "rectification" of the region occurs. We have designed experiments to test if such processes as rectification of "concerted evolution", co-evolution of a repeated gene family within a species, act on the Ty elements of yeast.