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WIREs Syst Biol Med
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The cell as the mechanistic basis for evolution

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Abstract The First Principles for Physiology originated in and emanate from the unicellular state of life. Viewing physiology as a continuum from unicellular to multicellular organisms provides fundamental insight to ontogeny and phylogeny as a functionally integral whole. Such mechanisms are most evident under conditions of physiologic stress; all of the molecular pathways that evolved in service to the vertebrate water–land transition aided and abetted the evolution of the vertebrate lung, for example. Reduction of evolution to cell biology has an important scientific feature—it is predictive. One implication of this perspective on evolution is the likelihood that it is the unicellular state that is actually the object of selection. By looking at the process of evolution from its unicellular origins, the causal relationships between genotype and phenotype are revealed, as are many other aspects of physiology and medicine that have remained anecdotal and counter‐intuitive. Evolutionary development can best be considered as a cyclical, epigenetic, reiterative environmental assessment process, originating from the unicellular state, both forward and backward, to sustain and perpetuate unicellular homeostasis. WIREs Syst Biol Med 2015, 7:275–284. doi: 10.1002/wsbm.1305 This article is categorized under: Biological Mechanisms > Cell Signaling Models of Systems Properties and Processes > Mechanistic Models Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models
Ouoroboros, an ancient symbol depicting a serpent eating its own tail.
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Lipid‐calcium homeostasis to complex physiology. The ontogenetic and phylogenetic integration (∫) of calcium–lipid homeostasis, from unicellular organism incorporation of lipid into the plasmalemma to multicellular organism calcium/lipid epistatic homeostasis fostered the Evolution of metazoans. This figure, focuses on the specific stress of the water–land transition on the Evolution of a wide variety of organs‐ bone, lung, skin, kidney, adrenal‐ resulting from the duplication of the PTHrP Receptor gene in fish, followed by the βAdrenergic Receptor (βAR) gene, culminating in integrated physiology, or allostasis (on far right). Internal selection was mediated through selection pressure on homeostatic mechanisms mediated by paracrine cell–cell interactions; as vertebrates adapted to land, the PTHrP signaling mechanism iteratively allowed for physiologic adaptations to air breathing (skin, lung), prevention of dessication (skin, kidney) and ‘fight or flight’ (adrenal). The blue arrows on the far left signify how evolved traits refer back to their antecedents, or are exapted.
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Models of Systems Properties and Processes > Mechanistic Models
Biological Mechanisms > Cell Signaling
Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models

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