MUTUALLY EXCLUSIVE EXON USE AND REACTIVE CENTER DIVERSITY IN INSECT SERPINS

We have isolated 38 cDNA clones for serpins from a lepidopteran insect , Manduca sexta, and have found that they are identical in sequence, e xcept for a region encoding the carboxyl-terminal 40-45 residues, whic h includes the reactive center. Among these clones, there are 11 varia nts of the reactive center region, each encoded by a different version of the ninth exon in the serpin gene. Thus, evolution of this insect serpin gene has resulted from duplication and sequence divergence of o nly the exon encoding the reactive site. Alternative pre-mRNA splicing then generates inhibitor diversity and the potential to regulate a va riety of proteinases, using the same protein framework joined to diffe rent reactive site region cassettes.