Widespread occurrence of serpin genes with multiple reactive centre-containing exon cassettes in insects and nematodes.

By applying homology-search and text-mining programs we have found that the Drosophila serine protease inhibitor (serpin) gene sp4 harbours four reactive centre-coding exons. The mutually exclusive use of these cassettes in combination with alternatively selectable exons at the 5'-end or in the 3'-untranslated region of the gene allows generation of more than ten different transcripts, all of which are expressed in Drosophila embryos. These transcripts may code for eight different Sp4 protein isoforms with different biological functions, which - dependent on the splice pattern - either may be secreted, reside in the endoplasmic reticulum, or may be located in the cytoplasm. An examination revealed the presence of two serpin genes, each coding for two or three likely alternative reactive centre exon cassettes, respectively, also in the Caenorhabditis elegans genome. The occurrence of such serpin genes in some groups of metazoa reflects a parsimonious way to enlarge the adaptive ability of these organisms to cope with a plethora of different serine and cysteine proteases.