Pleiotropy as the Mechanism for Evolving Novelty: Same Signal, Different Result

Abstract

In contrast to the probabilistic way of thinking about pleiotropy as the random expression of a single gene that generates two or more distinct phenotypic traits, it is actually a deterministic consequence of the evolution of complex physiology from the unicellular state. Pleiotropic novelties emerge through recombinations and permutations of cell-cell signaling exercised during reproduction based on both past and present physical and physiologic conditions, in service to the future needs of the organism for its continued survival. Functional homologies ranging from the lung to the kidney, skin, brain, thyroid and pituitary exemplify the evolutionary mechanistic strategy of pleiotropy. The power of this perspective is exemplified by the resolution of evolutionary gradualism and punctuated equilibrium in much the same way that Niels Bohr resolved the paradoxical duality of light as Complementarity.

Keywords: adipocyte differentiation related protein; cell-cell interaction; growth factor; growth factor receptor; neutral lipid trafficking; parathyroid hormone-related protein; pleiotropy; prostaglandin E2; type IV collagen; β-adrendergic receptor.

Figure 1

Pleiotropy as a Rubik Cube.

Figure 2

Origins of Vertebrate Physiologic Homologies. Sterols (far left) under the control of Hypoxia Inhibitory Factor-1 (Hif-1) link prokaryotes and eukaryotes together functionally; thus the major vertebrate physiologic homologies are linked through the induction of endothermy (top solid arrow) by atmospheric oxygen (bottom arrow). In the center of the Schematic is the molecular regulation of alveolar surfactant production. It is homologous with brain (neuregulin (NRG), and skin (tubular myelin (tm), both of which are under Parathyroid Hormone-related Protein (PTHrP) regulation. Lung and bone share functional homology through PTHrP stretch-regulated metabolism. Prostaglandin E2, leptin, Adipocyte Differentiation Related Protein (ADRP) and βAdrenergic Receptor (βAR) share homologies with fat pad Free Fatty Acid (FFA) regulation. The lung and kidney share functional homologies through PTHrP and Type IV Collagen (Goodpasture’s Syndrome). Periods of hypoxia due to lung evolution caused physiologic stress, stimulating the Pituitary-Adrenal Axis production of epinephrine, which both relieved the constraint on the alveoli by stimulating surfactant secretion, and stimulated peripheral fat cell secretion of FFAs, causing increased metabolic activity and body heat = endothermy.