Cuticle protein genes of Drosophila: structure, organization and evolution of four clustered genes.

Most of a 9 kb region of the Drosophila genome containing genes for several cuticle proteins has been sequenced. Five cuticle-gene-like sequences have been identified and mapped. Amino acid sequences of four of the five major third instar cuticle proteins have been determined. These four sequences are identical with those predicted from the sequences of four of the five genes. Two cuticle genes are transcribed in one direction and two in the opposite direction. The fifth cuticle-like gene is judged to be a pseudogene because several features of its structure and the absence of detectable transcripts suggest it is nonfunctional. Sequence comparisons indicate that it arose by an unequal crossing-over event involving two closely related and adjacent cuticle genes. Each of the four cuticle genes contains a signal peptide coding sequence interrupted by a short intervening sequence (about 60 bp) at a conserved site. Conserved sequences occur in the 5' mRNA untranslated region, in the adjacent 35 bp of upstream flanking sequence and at -200 bp from the mRNA start position in each of the cuticle genes. We discuss the structure, organization and evolution of these cuticle genes as a model small gene family.