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.
Highlights
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 a deterministic consequence of the evolution of complex physiology from the unicellular state
In the book Evolutionary Biology, Cell-Cell Communication, and Complex Disease [9], the pleiotropic property of biology was utilized to explain the evolutionary mechanisms for both physiology and pathophysiology. In the former case, our work demonstrated how the alveolus of the lung and the glomerulus of the kidney are virtually the same functionally at the cell signaling level [9,15,16], even though they nominally seem to be structurally and functionally unrelated when seen from a descriptive perspective—one mediates gas exchange between the environment and the circulation, the other mediates fluid and electrolyte balance in the systemic circulation
Regarding the physiologic commonalities between the lung and kidney, in the case of the lung, the stretch-regulated Parathyroid Hormone-related Protein (PTHrP) produced by the epithelial type II cell feeds-back to its receptor on the lipofibroblast to regulate lung surfactant production, reducing surface tension to maintain alveolar homeostasis [21]; in the case of the kidney, PTHrP produced by the epithelial podocytes that surround the fluid-filled space within the glomerulus regulate the mesangium, the thin mesodermal membrane supporting the glomerular capillary loops, homeostatically monitoring and regulating fluid and electrolyte balance in the systemic circulation [22]
Summary
Erno Rubik invented his eponymous “cube” (Figure 1) to teach his students about spatial relationships and Group Theory [3]. In the book Evolutionary Biology, Cell-Cell Communication, and Complex Disease [9], the pleiotropic property of biology was utilized to explain the evolutionary mechanisms for both physiology and pathophysiology In the former case, our work demonstrated how the alveolus of the lung and the glomerulus of the kidney are virtually the same functionally at the cell signaling level [9,15,16], even though they nominally seem to be structurally and functionally unrelated when seen from a descriptive perspective—one mediates gas exchange between the environment and the circulation, the other mediates fluid and electrolyte balance in the systemic circulation. Regarding the physiologic commonalities between the lung and kidney, in the case of the lung, the stretch-regulated PTHrP produced by the epithelial type II cell feeds-back to its receptor on the lipofibroblast to regulate lung surfactant production, reducing surface tension to maintain alveolar homeostasis [21]; in the case of the kidney, PTHrP produced by the epithelial podocytes that surround the fluid-filled space within the glomerulus regulate the mesangium, the thin mesodermal membrane supporting the glomerular capillary loops, homeostatically monitoring and regulating fluid and electrolyte balance in the systemic circulation [22]
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