Novel protein domains and repeats in Drosophila melanogaster: Insights into structure, function, and evolution

Sequence database searching methods such as BLAST, are invaluable for predi cting molecular function oil the basis Of Sequence similarities among singl e regions of proteins. Searches of whole databases however, are not optimiz ed to detect multiple homologous regions within a single polypeptide. Here we have used the prospero algorithm to perform self-comparisons of all pred icted Drosophila melanogaster gene products. Predicted repeats, and their h omologs from all species, were analyzed further to detect hitherto unapprec iated evolutionary relationships. Results included the identification of no vel tandem repeats in the human X-linked retinitis pigmentosa type-2 gene p roduct, repeated segments in cystinosin, associated with a defect in cystin e transport, and 'nested' homologous domains in dysferlin, whose gene is mu tated in limb girdle muscular dystrophy. Novel signaling domain families we re found that may regulate the microtubule-based cytoskeleton and ubiquitin -mediated proteolysis, respectively. Two families of glycosyl hydrolases we re shown to contain internal repetitions that hint at their evolution via a piecemeal, modular approach. In addition, three examples of fruit fly gene s were detected with tandem exons that appear to have arisen via internal d uplication. These findings demonstrate how completely sequenced genomes cal l be exploited to further understand the relationships between molecular st ructure, function, and evolution.