Analyses of the Serpin Gene Family in the African Malaria Vector Mosquito, Anopheles gambiae

Abstract

Serpins regulate some innate immune responses of insects, apparently by inhibiting endogenous serine proteases. In the mosquito Anopheles gambiae, 14 serpin genes were initially predicted upon completion of the genome project. We have identified 18 serpin genes, all on chromosomes 2 and 3, through searches of genomic DNA and EST databases. We completed sequencing of cDNAs for most of the An. gambiae serpins, to check gene predictions and to obtain more complete sequence information. Sixteen of the serpins contain putative secretion signal sequences. Multiple sequence alignment of the reactive site loop region indicates that most of the An. gambiae serpins may be inhibitory and allows initial predictions about their selectivity. Phylogenetic analyses confirmed that serpin-1, 2, 3, 8, 9 and 10 formed phylogenetic clusters with known inhibitory serpins from Drosophila melanogester and Manduca sexta. Many serpins were expressed during all life stages. However, serpin-7, 8, 12, and 19 were expressed very low in the adult stage, whereas serpin-13 was expressed mostly in eggs and young larvae, and serpin-5 and 14 mostly in adults. Such differences in expression pattern indicate that the serpins are involved in multiple physiological processes. Determining the biological functions of the mosquito serpins will require future work to identify the proteases they inhibit in vivo.