Structure of two related rat pancreatic trypsin genes.

A family of approximately 10 trypsin genes was detected in a rat genomic library by hybridization and in vivo recombination techniques using cloned rat pancreatic trypsin I and II cDNAs as probes. Two separate clones containing the entire trypsin I gene and most of the trypsin II gene were sequenced. Four introns split the trypsin I coding sequence. The positions of the first three introns of the trypsin II gene are identical with those in the trypsin I gene (the fourth intron was not present in the trypsin II clone). The coding regions of the two genes are 88% homologous; the 5'-noncoding regions are 92% homologous, whereas the 3'-noncoding regions share 66% identity. In contrast, the proximal 5'-flanking regions from -1 to -500 which may contain the elements controlling gene expression are less than 30% conserved overall, but segments of approximately 70% homology can be discerned in this region. Some of these sequences are homologous to sequences found in the chymotrypsin and elastase genes. More distal upstream sequences (-500 to -2500) and the intervening sequences show no evident sequence homology (less than 20%). Unique sequences containing homopolymeric purine/pyrimidine repeats are found 2.5 kilobases upstream from the start of transcription of the trypsin I gene and within the second and third introns of the trypsin II gene. The nucleotide homologies as well as the similarities of intron positions of the two trypsin genes to those of other serine protease genes clearly support an evolutionary relationship between members of this gene family.