reading

Cover
Preface
1 A Brief History of Evolutionary Thinking
1. Summary
2. Introduction
3. Darwin
4. Darwin’s Theory
5. The Modern Synthesis
6. The Darkest Chapter
7. Conclusions
8. References
2 Outlining the Major Transitions in the History of Life
1. Summary
2. Introduction
3. The Major Transitions
4. Conclusions
5. References
3 One Central Mystery
1. Summary
2. Introduction
3. Conclusions
4. References
4 A Levels‐of‐Selection View of Evolutionary Physiology
1. Summary
2. Conclusions
3. References
5 The Cell as the Smallest Functional Unit of Biology/Physiology
1. Summary
2. In the Beginning
3. The Advent of Multicellularity
4. Evolution: Cellular Style
5. The Water–Land Transition and Vertebrate Evolution
6. The Cellular Approach to Evolution Is Predictive
7. We Are Not Just in This Environment, We Are of It
8. Bioethics Based on Evolutionary Ontology and Epistemology, Not Descriptive Phenotypes, and Genes
9. The Theory of Everything (TOE)
10. Coda
11. References
6 Development of Tissues and Organs
1. Summary
2. Introduction
3. Lung Alveolar Morphogenesis
4. Parathyroid Hormone‐Related Protein
5. Stretch‐Induced Cell–Cell Interactions
6. References
7 When Homeostasis Fails
1. Summary
2. Introduction
3. Peroxisome Proliferator Activated Receptor Gamma as a Connection to the Evolution of the LIF
4. PPARγ, Statins, and TOR as Mechanisms for Homeostasis
5. Pleiotropy: The Deus ex Machina (Ghost in the Machine)
6. Rubik’s Cube as a Metaphor for Pleiotropic Evolution
7. The Lung as the Prototypical Pleiotropic Mechanism
8. The Lung as an Interactive Barrier: Homolog of the Plasma Membrane, Skin, and Brain
9. NKX2.1, Thyroid, Pituitary, and Lung Pleiotropy
10. The Phylogeny of the Thyroid
11. An Evolutionary Vertical Integration of the Phylogeny and Ontogeny of the Thyroid
12. A Retrospective Understanding of Evolution
13. Denouement
14. Conclusions
15. References
8 Wnt Signaling During Development
1. Summary
2. Introduction
3. Role of Growth Factors in Alveolar Homeostasis
4. The Kidney Glomerulus as a Homolog of the Lung Alveolus
5. Pathologic Consequences of Failed Paracrine Signaling
6. Reference
9 Integrated Regulation of Homeostasis – Vascular, Nervous, Endocrine, Neuroendocrine, Autonomic
1. Summary
2. Introduction
3. Water–Land Transition as the Catalyst for Vertebrate Evolution
4. Parathyroid Hormone‐Related Protein Signaling Is Key to Understanding the Evolution of the Lung
5. The Physics of Lung Evolution
6. Functional Homology between Membrane Lipids and Oxygenation
7. Atmospheric Oxygen, Physiologic Stress, Gene Duplication, and Lung Evolution
8. Duplication of the β Adrenergic Receptor and the Glucocorticoid Receptor Genes
9. Evolution of Endothermy/Homeothermy as Evidence for the Effect of Stress on Vertebrate Physiologic Evolution
10. Hibernation as Reverse Evolution
11. Predictive Power of the Cellular–Molecular Approach to Evolution
12. Conclusions
13. References
10 Endogenous and Exogenous Mechanisms for Healing
1. Summary
2. Introduction
3. Endogenous Mechanisms for Healing
4. Exogenous Mechanisms for Healing Using Evolutionary Principles
5. References
11 Systems Biology as Recapitulation of Ontogeny and Phylogeny
1. Summary
2. Introduction
3. A Paradigm Shift in Evolution
4. Endothermy as “Proof of Principle” for the Evolution of Serial Exaptations
5. Endothermy Defies Physics, Fostering Migration
6. Conclusions
7. References
12 Terminal Addition as Physiologic Homeostasis and Regeneration, or Evolutionary Medicine
1. Summary
2. Introduction
3. Conflicting Viewpoints
4. Terminal Addition as a Perpetual Cellular Link with the Environment
5. Terminal Addition as Layered Cell–Cell Signaling
6. Epigenetic Impacts and Terminal Addition
7. Physiologic Stress, Vascular Shear Stress, Radical Oxygen Species, and Mutation within Constraints = The Mechanism of Terminal Addition
8. Homeobox Genes, Colinearity, and Terminal Addition
9. The Alveolar Lipofibroblast as Terminal Addition
10. The Participation of Glomerular Mesangial Cells
11. PTHrP Effects on the Anterior Pituitary, Adrenal Cortex, and Adrenal Medulla
12. Catecholamines, Lung, and Heart Biology
13. Oxytocin, Endothermy, and the Retina
14. Central Nervous System
15. Terminal Addition, “Reverse Evolution,” and Evolutionary Medicine
16. Discussion
17. Terminal Addition: The Fundament of Haeckel’s Biogenetic Law
18. Somewhere between Gene and Phenotype Lies the Process of Evolution
19. Conclusions
20. References
13 Phantom Limbs
1. Summary
2. Introduction
3. Background to Phantom Limb Sensation
4. Relevance of Phantom Limb Sensation to Terminal Addition
5. Phantom Limb Sensation as Non‐Localization
6. Limbs and Hearts
7. Relationship of Limbs to Bipedalism and the Evolution of Birds and Mammals
8. Of Limbs and Consciousness
9. Life as Fractals
10. Consciousness, the Epitome of the Continuum from Inanimate to Animate
11. References
14 Man’s Place in the Universe
1. Summary
2. Introduction
3. Anthropomorphisms Subvert the Biologic Imperative to Cooperate
4. Euphysiology
5. References
15 Evolution, Deception, and Public Health
1. Summary
2. Part I. Deception Is Deceiving: The Exception that Proves the Rule
3. Part II. Resolution of the Ambiguities by Assimilating the Deception
4. Part III. Deception and Public Health
5. Part IV. Prediction: Bioethics Based on First Principles of Physiology
6. References
Index
End User License Agreement

List of Illustrations

Chapter 01
1. Figure 1.1 The geological time scale. Originally based on relative time derived from uniformitarian principles, radiometric dating of geological strata now allows both relative and chronological time measures. Newly ratified periods of the Proterozoic (e.g. the Cryogenian) are based not on stratigraphic events but on measures of chronological time.
2. Figure 1.2 A phylogenetic tree. Analogous to the fossil record, time proceeds from bottom to top, while diversity and disparity are measured on the x‐axis. A stem group diverges from its sister group while deriving novel character states (horizontal bars). The stem group taxa are entirely extinct. The last common ancestor (LCA) shares all the derived character states with the crown group, which includes all living and some extinct members of the group or clade.
Chapter 02
1. Figure 2.1 Major transitions in the history of life. The origin of life entailed groups of replicating molecules. These groups of molecules formed simple cells. Simple cells banded together in complex cells that became eukaryotes. Eukaryotes repeatedly formed multicellular organisms. The advantages of size increase favored each transition, while conflicts among lower‐level units hindered them.
2. Figure 2.2 A description of life. All living things need to take up energy from the environment and convert it into a useable form; some of this energy is then used to replicate life’s informational content.
3. Figure 2.3 A trait‐group model of group selection. Two types of molecules exist in a population. Cooperators (circles with arrows) convert energy and release energy‐rich products into the environment. Defectors (circles) rely on these products for their own replication. The latter are favored by within‐group competition, while the former are favored by between‐group competition.
4. Figure 2.4 The stochastic corrector model. A replicator (circles with arrows) gives rise by mutation to a second replicator (circles without arrows), which replicates more efficiently and faster. Protocells, however, divide when the number of replicators is small, allowing cells with equal numbers of replicators to form purely by chance. If replicators complement each other catalytically, selection will favor the cells with equal numbers.
5. Figure 2.5 Surface‐to‐volume constraints. In a spherical cell, surface area (A) increases as the square of the radius, while volume (V) increases as the cube. Prokaryotes with external, energy‐converting membranes cannot easily increase in size.
6. Figure 2.6 The perils of cells within cells. A cell (red) uses the products of energy conversion for its own selfish replication.
Chapter 03
1. Figure 3.1 A phylogeny of eukaryotes (excavates + SAR + plants + amoebozans + opisthokonts). Multicellular eukaryotes evolved repeatedly in SAR (= stramenopiles, alveolates, and rhizaria), plants, amoebozoans, and opithokonts.
2. Figure 3.2 Conflict and conflict mediation in the emergence of biological units [7].
3. Figure 3.3 Eukaryogenesis following environmental release. The lifting of an environmental barrier allowing the formation of large, complex cells would have led to numerous lineages becoming eukaryotes.
4. Figure 3.4 Circumventing surface‐to‐volume constraints in the origin of eukaryotes. By moving small, energy‐converting cells inside a larger cell, surface‐to‐volume constraints could be alleviated, and the complex cell could grow to larger sizes.
5. Figure 3.5 Eukaryotic sex allows symbiont migration. Two eukaryotic cells fuse during sex and energetically selfish symbionts migrate from one cell to the other.
6. Figure 3.6 Co‐option of calcium signaling by proto‐mitochondria. To maintain metabolic homeostasis, a proto‐mitochondrion near the external membrane (a) takes up calcium ions and pumps them back out. This depolarizes its membrane. A proto‐mitochondrion distant from the membrane (b) cannot do this. Membrane hyper‐polarization leads to excessive production of reactive oxygen species. Another proto‐mitochondrion (c) survives by loose‐coupling between substrate oxidation and proton extrusion.
Chapter 04
1. Figure 4.1 Surface‐to‐volume constraints again. A chain or sheet of cells has relatively more surface relative to volume than a single large cell.
2. Figure 4.2 Contrasting views of the relationships of the five early‐diverging groups of animals. The “sponge sister” view (a) and the “ctenophore sister” view (b) agree that animals are monophyletic and sister to choanoflagellates but differ in the placement of the group sister to all other animals.
3. Figure 4.3 A simple colony of choanoflagellates.
4. Figure 4.4 Complexity and conflict. Multicellular organisms meet the physiological requirements of individual cells by differentiating some cells into physiological systems. Complexity and cell–cell conflicts both increase. Mediation of cell–cell conflicts also increases complexity.
Chapter 05
1. Figure 5.1 Ouroboros. After the Greek legend of a snake catching its tail.
2. Figure 5.2 From lipid–calcium homeostasis to complex physiology. The ontogenetic and phylogenetic integration (∫) of calcium–lipid homeostasis, from unicellular organism incorporation of lipid into the plasma lemma 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 β adrenergic 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.
Chapter 06
1. Figure 6.1 Cell–Cell Communication and Lung Embryogenesis. Depicted here (from the top down) is the development of the intact lung mediated by endodermal–mesodermal interactions. In contrast, the isolated endoderm and mesoderm, respectively, do not develop in isolation, whereas the recombination of these tissue layers will develop comparably with the intact tissue.
2. Figure 6.2 Mesodermal–Endodermal Growth Factor‐Receptor Interactions Mediate Lung Alveolar Development. Triggered by the distension of the alveolar wall, [1] parathyroid hormone‐related protein (PTHrP) produced by the endoderm [2] binds to its receptor on the mesoderm [3], stimulating uptake and storage of neutral lipid [4]. Prostaglandin E₂[5] produced by the endoderm binds to its receptor on the mesoderm [6], stimulating the release of lipid‐bound adipocyte differentiation related protein (ADRP) [7]. Leptin [8] secreted by the mesoderm binds to its receptor on the endoderm [9], stimulating neutral lipid incorporation into surfactant phospholipid [10], which is subsequently secreted into the alveolar space [11].
Chapter 07
1. Figure 7.1 The Evolutionary Mechanism of Pleiotropy. The pleiotropic distribution of a gene (symbolized by a “gear” on the surface of a Rubik’s Cube) within the organism is determined by its utility during evolution. The gene may have subsequently been co‐opted for a different biologic trait necessitated by the prevailing environmental conditions. Under different environmental conditions, that same gene may have been delegated for a different purpose (depicted by the “twisting of the Rubik’s Cube,” changing the distribution of the gene on the surface of the cube), bearing in mind that the process must always comply with the First Principles of Physiology. That centralized control is the key to understanding the integrated homeostatic control of physiology.
2. Figure 7.2 Homology between Alveolus and Glomerulus. Both structures are “stretch” transducers whose function is mediated by PTHrP signaling. Loss of PTHrP signaling causes “default” of the specialized fibroblast to a myofibroblast (depicted as a brown fibrous cell dominated by the Wingless/Int (Wnt) pathway, characteristic of fibrosis.
3. Figure 7.3 Alveolar Evolution. The top of the schematic describes the cellular development of the alveolus. Below it are the mesenchymal–epithelial interactions that caused the developmental and phylogenetic adaptations over the course of vertebrate evolution. The progressive decrease in alveolar diameter increased the surface area to blood volume ratio, facilitating gas exchange in support of metabolic demand over the course of vertebrate evolution from water to land.
4. Figure 7.4 Homology between the Swim Bladder and Lung. The swim bladder of physostomous fish (left) develops as an out‐pouching of the esophagus to form an inflatable structure that facilitates gas exchange for buoyancy, maximizing metabolic activity in water. The surface of the swim bladder is coated with surfactant to prevent the walls of the bladder from adhering to one another. The lung (right) is also an out‐pouching of the esophagus, the alveoli mediating gas exchange for optimally metabolic function.
5. Figure 7.5 Homology between Lung and Skin. The skin and lung are barriers between the external and internal environments. The stratum corneum of the skin forms a lipid barrier containing antimicrobial peptides, and the alveolus generates surfactant, which has the same property. In both cases, the epithelium synthesizes and secretes lamellar bodies (red arrows) composed of lipids complexed with defensins to prevent microbial invasion.
6. Figure 7.6 Phylogenetic Homology between Thyroid, Lung, and Pituitary Based on Nkx 2.1/TTF‐1. The thyroid, lung, and pituitary all develop from the foregut under the genetic control of Nkx 2.1/TTF‐1.
Chapter 12
1. Figure 12.1 Lung Biologic Continuum from Ontogeny–Phylogeny to Homeostasis and Repair. The schematic compares the cellular–molecular progression of lung evolution from the fish swim bladder to the mammalian lung (left portion) with the development of the mammalian lung, or Evo‐Devo, as the alveoli become progressively smaller (see legend in upper left corner), increasing the surface area–blood volume ratio. This is facilitated by the decrease in alveolar myofibroblasts and the increase in lipofibroblasts, due to the decrease in Wingless/int (Wnt) signaling and increase in PTHrP signaling, respectively. Lung fibrosis progresses in the reverse direction (lower left corner). Lung homeostasis (right portion) is characterized by PTHrP/leptin signaling between the type II cell and lipofibroblast, coordinately regulating the stretch regulation of surfactant production and alveolar capillary perfusion. Failure of PTHrP signaling causes increased Wnt signaling, decreased PPAR γ expression by lipofibroblasts, and transdifferentiation to myofibroblasts, causing lung fibrosis. Repair (arrow from homeostasis back to ontogeny–phylogeny) is the recapitulation of ontogeny–phylogeny, resulting in increased PPARγ expression.
Chapter 14
1. Figure 14.1 From the Big Bang to social systems. On the far left is the Big Bang of the Universe, which scattered the elements based on their atomic mass, creating an informatic hierarchy. Biology exploited the physical environment to generate autonomous cells that used homeostasis to maintain negentropy. Competition between prokaryotes and eukaryotes gave rise to multicellular organisms, which ultimately formed social systems, all based on the First Principles of Physiology.
2. Figure 14.2 Alternating extrinsic and intrinsic selection pressures for the genes of lung phylogeny and ontogeny. The effects of the extrinsic factors (salinity, land nutrients, and oxygen on the x‐axis) on genes that determine the phylogeny and ontogeny of the mammalian lung alternate sequentially with the intrinsic genetic factors (y‐axis), highlighted by the squares and circles, respectively. Steps 1–11 appear in the sequence they appear during phylogeny and ontogeny: (1) AMPs; (2) VDR; (3) type IV collagen; (4) GR; (5) 11β HSD; (6) βAR; (7) ADRP; (8) leptin; (9) leptin receptor; (10) PTHrP; and (11) SP‐B. Steps 12–17 represent the pleiotropic effects of leptin on the Epidermal Growth Factor (EGF) in oval signaling pathways integrating steps 1–6, 10, and 11. Steps 18–20 are major geologic epochs that have “driven” intrinsic lung evolution [3].

This edition first published 2019
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