title: Functional diversification of a protease inhibitor gene in the genus Drosophila and its molecular basis.
abstract: The mutually exclusive use of alternative reactive site loop (RSL) cassettes due to alternative splicing of serpin (serine protease inhibitor) gene transcripts is a widespread strategy to create target-selective protease inhibitors in the animal kingdom. Since molecular basis and evolution of serpin RSL cassette exon amplification and diversification are unexplored, the exon-intron organization of the serpin gene spn4 from 12 species of the genus Drosophila was studied. The analysis of the gene structures shows that both number and target enzyme specificities of Spn4 RSL cassettes are highly variable in fruit flies and includes inhibitor variants with novel antiproteolytic activities in some species, indicating that RSL diversity is the result of adaptive evolution. Comparative genomics suggests that interallelic gene conversion and/or recombination events contribute to RSL cassette exon amplification. Due to an intron that is located at the most suitable position within the RSL region, multiple inhibitors can be formed in an economic manner that are both efficient and target-selective, allowing fruit flies to control an astonishing variety of proteases with different cleavage chemistry and evolutionary ancestry.
authors.affiliation: Department of Biotechnology, Faculty of Technology, Bielefeld University, D-33501 Bielefeld, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Börner
authors.forename: Hermann
authors.initials: H
authors.lastname: Ragg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D004330:Drosophila / Q000235:genetics*; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics; D017344:Genes, Insect; D014644:Genetic Variation; D023281:Genomics; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D015843:Serpins / Q000737:chemistry / Q000235:genetics*
chemical_list: D020033:Protein Isoforms; D015843:Serpins