Evolution of Proenkephalin and Prodynorphin

SYNOPSIS. Since the discovery of the enkephalins in 1975, threeseparate families of opioid peptides have been identified, proopiomelanocortin,proenkephalin, and prodynorphin. The lattertwo have multiplecopies of the enkephalin sequence in larger enkephalin containingpolypeptides (ECPs). The amino acid and nucleotide sequencesof these two proteins from human as well as other species havebeen determined. A comparison of each of the proteins betweenspecies indicates a number of highly conserved regions in notonly the bioactive peptides but at other locations as well.A number of common features between the two proteins suggesteda common ancestral protein. Using computeraided metric analysis,it is possible to align their DNA segments so thatthe cysteineresidues at the amino end are aligned, as well as the enkephalinsequences at the carboxyl end. The exact alignment of the centralregions is currently being studied. Metric analysis thus providesstrong evidence that proenkephalin and prodynorphin divergedfrom a single ancestral protein.