Primary structure of the human renin gene.

The gene encoding human renin has been isolated on two overlapping clones from a bacteriophage lambda library of human DNA. The entire gene spans about 12,000 bp and contains 10 exons separated by 9 intervening sequences. The gene structure is similar to that of human pepsinogen in terms of overall size, homology in the coding regions, position of introns, and sizes of the exons, suggesting that the two genes are evolutionarily related. However, a novel exon coding for only three amino acids was detected that is not present in the pepsinogen gene and whose amino acids are also not found in mouse renin. Although the nucleotide sequence of the 5'-flanking DNA differs from that of the pepsinogen gene, in both cases this region contains a structure of almost perfect dyad symmetry which immediately precedes the TATA box and may have functional importance. Furthermore, sequences resembling the putative consensus sequence for glucocorticoid regulation of gene expression are located approximately 200 and 300 bp upstream from the gene. The overall structural anatomy suggests that the human renin gene evolved by mechanisms that include a duplication of exon segments, particularly those containing the codons for the catalytically important aspartate residues, together with the insertion of other exon and flanking DNA structures. An analysis of human chromosomal DNA demonstrates that there is only one gene with high homology to human renin.