MOLECULAR CHARACTERIZATION AND PHYSIOLOGICAL REGULATION OF A TATA-LESS GENE ENCODING CHICKEN GASTRIN

Avian gastrin is a gastric acid secretagogue, but is structurally more closely related to mammalian cholecystokinin, which is functionally d istinct from gastrin. This apparently anomalous structure/activity rel ationship raises important issues for understanding the evolution of r egulatory peptides and the mechanisms that control their expression. T o clarify the possible mechanisms, we have determined the sequence of a 6.5-kb BamHI genomic DNA fragment that includes the entire avian gas trin transcriptional unit. The complete cDNA sequence, determined by a nchored PCR, encoded a precursor of 105 amino acids. Conserved primary amino acid structures were limited to a decapeptide determining biolo gical activity, and essential sites for post-translational processing. Significantly, however, the genomic regulatory regions, and introns, were unlike those of any previously reported gastrin/cholecystokinin g ene. The avian gastrin ene contained no recognizable TATA-box motif, a feature unique to this gene family, but had a G+C-rich region immedia tely upstream of the transcription initiation site, and a Z-DNA purine -pyrimidine repeat sequence. Moreover, physiological regulation of the avian gastrin gene differed markedly from that observed in mammals, i n that the important local paracrine downregulation by antral somatost atin was absent; instead, evidence for a hormonal regulation was demon strated. The data indicate that genomic regulatory elements within reg ulatory peptide families such as the gastrin/cholecystokinin family, a nd mechanisms of physiological control, are not conserved during evolu tion, even though biologically important amino acid sequence informati on is retained.