Primary Structure of the Human Renin Gene

Abstract

The gene encoding human renin was isolated on 2 overlapping clones from a bacteriophage .lambda. library of human DNA. The entire gene spans .apprx. 12,000 bp [base pairs] 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 size of the exons, suggesting that the 2 genes are evolutionarily related. A novel exon coding for only 3 amino acids was detected that is not present in the pepsinogen gene and whose amino acids were 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. Sequences resembling the putative consensus sequence for glucocorticoid regulation of gene expression were located .apprx. 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 Asp residues, together with the insertion of other exon and flanking DNA structrues. An analysis of human chromosomal DNA demonstrates that there is only 1 gene with high homology to human renin.