-crystallin of the scallop lens is an inactive aldehyde dehydrogenase (ALDH1A9). Here we have cloned the scallop -crystallin gene. Except for an extra novel first exon, its 14 exon structure agrees well with that of mammalian ALDH1, 2 and 6. The -2120/+63, -714/+63 and -156/+63 -crystallin promoter fragments drive the luciferase reporter gene in transfected TN4-1 lens cells and L929 fibroblasts, but not in Cos7 cells. Putative binding sequences for CREB/Jun, ACRYBP1, AP-1 and PAX6 in the -crystallin promoter are surprisingly similar to the cis-elements used for lens promoter activity of the mouse and chicken A-crystallin genes, which encode proteins homologous to small heat shock proteins. Site-specific mutations in the overlapping CREB/Jun and Pax6 sites abolished activity of the -crystallin promoter in transfected cells. Gel shift experiments utilizing extracts from the TN4-1, L929 and Cos7 cells and the scallop stomach, and oligonucleotides derived from the putative binding sites of the -crystallin promoter, showed complex formation. Gel shift experiments showed binding of recombinant Pax6 and CREB to their respective sites. Our data suggest convergent evolutionary adaptations that underlie the preferential expression of crystallin genes in the lens of vertebrates and invertebrates.