Molecular Evolution of the Polypetide Hormones

Any biological function is at least bimolecular and its evolution therefore is at least dual, with variations in two lines of molecules. The hormone specificity results from a particular fit between the three-dimensional structure of the agent and that of the receptor but, because receptors are not known at the structural level, a discussion on the evolution of the polypeptide hormones is mainly limited to the possible progressive changes of the latter. As for other proteins (enzymes, oxygen carriers etc.) two degrees of complexity can be distinguished according to whether the hormone comprises one or several polypeptide chains. Protein assembly can bring new biological properties, each subunit playing a particular role. In this case, the 'internal' evolution (chain-chain interactions) overlaps the 'external' evolution (hormone-receptor contacts). The 'monomeric' hormones present the following problems: evolution of the prohormone and of the converting enzyme (for insulin), duplication and differentiation of two lines of hormones either by amino acid substitutions (neurohypophysial hormones and neurophysins) or by substitutions and size modifications (corticotropin and lipotropin), duplication and fusion leading to internal homology in the single polypeptide chain (somatotropin, prolactin, placental lactogen). The 'dimeric' hormones lead to several problems: successive duplications giving different subunits, selective associations between subunits, unequal rates of evolution of the subunits, the function of each subunit (lutropin, follitropin, thyrotropin, choriogonadotropin). An attempt is made to integrate the evolution of polypeptide hormones in the frame of the evolution of proteins.