Structural analysis of the molecular evolution of some gastro-entero-pancreatic hormones

By means of a statistical analysis of the occurrence of amino-acid residues in the polypeptide chains of several gastro-entero-pancreatic (GEP) hormones an investigation was undertaken to determine whether any of these hormones might be related to each other--possibly from an evolutionary point of view. Particular interest was paid to the occurrence of small charged segments, i.e. those with acidic or basic amino acid residues, since such segments can be presumed to play a role in hormonal receptor binding mechanisms. By this method hormonal relationships were suggested by the observation that these small charged amino-acid sequences, contained in the hormonal structures, match as a result of non-randomness. It was found that hagfish and human insulin were related on a molecular level not only to the newly discovered (avian, bovine, human) pancreatic polypeptide (PP) but also to some other GEP hormones (VIP, GIP, glucagon) as well as to calcitonin and to the alpha-subunit of the glycoprotein hormones. Interpretation of the statistical data suggests that all these peptide hormones are related by a common hexapeptide sequence which contributed, at an evolutionary point, to their molecular architecture. A hexapeptide segment of APP is statistically related to a sequence of equal size in the carboxy terminal region of the A-chain of both hagfish and human insulin, providing the first instance of their structural similarity. Correlations between PP, insulin, glucagon, VIP, and calcitonin provide a tentative basis for predicting the production of one or more of these peptide hormones by immature or de-differentiated cells of neoplasms and non-neoplastic pathologic lesions of the GEP endocrine system.