Peptide self-aggregation and peptide complementarity as bases for the evolution of peptide receptors: a review

Abstract

This paper reviews the three major theories of peptide receptor evolution: (1) Dwyer's theory that peptide receptors evolved from self-aggregating peptides; (2) Root-Bernstein's theory that peptide receptors evolved from functionally and structurally complementary peptides; and (3) Blalock's theory that receptors evolved from hydropathically complementary sequences encoded in the antisense strand of the DNA encoding each peptide. The evidence to date suggests that the co-yevolution of peptides and their receptors is strongly constrained by one or more of these physicochemically based mechanisms, which argues against a random or frozen accident' model. The data also suggest that structure and function are integrally related from the earliest steps of receptor-ligand evolution so that peptide functionality is non-random and highly conserved in its origin. The result is a molecular paleontology' that reveals the evolutionary constraints that shaped the interaction of structure and function.

Compositional complementarity and prebiotic ecology in the origin of life

“…Novelty will be built in general from mixing and matching previously adaptive modules into evermore elaborate hierarchies of complexity. (87)(88)(89)(90) Experimental tests of composomal ecology Many possible tests, some retrodictive (that is regarding patterns that should exist within data already available) and some predictive, exist to differentiate our theory from other theories of the origins of life. We propose only a handful here.…”

Antigenic Complementarity in the Origins of Autoimmunity: A General Theory Illustrated With a Case Study of Idiopathic Thrombocytopenia Purpura

“…VWF and pgp1b do not appear to bind to each other according to hydropathic complementarity (data not shown). We have previously demonstrated that hydropathic complementarity cannot explain insulin -glucagon complementarity, nor the ability of these proteins to self-aggregate (Root-Bernstein 2005b). And there is clearly no application of the antisense concept to the interaction of myelin basic protein with MDP or other bacterial cell-wall derived adjuvants, which are primarily polysaccharide based.…”

The Challenge of Genetic Studies in Hypertension

“…They independently isolated, from cDNA libraries, identical DNA clones encoding single polypeptide receptors with dual peptide binding sites. 9,11 The MRT theory is controversial 29,30 and was not confirmed in the case of Ang II, vasopressin and other receptors. 30,31 Most evidence for the MRT is based on immunological techniques 30 and these methods are subject to question as mentioned above.…”

“…Moreover, many putative receptors isolated according to MRT theory have not turned out to be receptors. 30 This questions the universal applicability of MRT.…”