Evolutionary Biology
Cell-Cell Communication, and Complex Disease

Even in this advanced age of genomics, the evolutionary process of unicellular and multicellular organisms is continually in debate. Evolutionary Biology, Cell?Cell Communication, and Complex Disease challenges current wisdom by using physiology to present an integrative view of the nature, origins, and evolution of fundamental biological systems.

Providing a deeper understanding of the way genes relate to the traits of living organisms, this book offers useful information applying evolutionary biology, functional genomics, and cell communication studies to complex disease. Examining the 4.5 billion-year evolution process from environment adaptations to cell-cell communication to communication of genetic information for reproduction, Evolutionary Biology hones in on the "why and how" of evolution by uniquely focusing on the cell as the smallest unit of biologic structure and function.

Based on empirically derived data rather than association studies, Evolutionary Biology covers:

• A model for forming testable hypotheses in complex disease studies

• The integrating role played by the evolution of metabolism, especially lipid metabolism

• The evolutionary continuum from development to homeostasis

• Regeneration and aging mediated by signaling molecules

Ambitious and game-changing Evolutionary Biology suggests that biology began as a mechanism for reducing energy within the cell, defying the Second Law of Thermodynamics. An ideal text for those interested in forward thinking scientific study, the insights presented in Evolutionary Biology help practitioners effectively comprehend the evolutionary process.

About the Authors xiii

1 THE CELLULAR ORIGIN OF VERTEBRATES 1

The Origins of Unicellular Life on Earth 1

Prokaryotes versus Eukaryotes 4

Coevolution of traits 5

Cholesterol Facilitates Lipid Rafts for Cell–Cell Communication 7

The Endomembrane System 9

The Cellular Mechanism of Evolution 10

Why Evolve? 11

Cell–Cell Communication and Aging 12

2 REDUCING LUNG PHYSIOLOGY TO ITS MOLECULAR PHENOTYPES 17

Hormonal Acceleration of Lung Development 17

Neutral Lipid Traffi cking and Lung Evolution 19

Other Examples of Cellular Cooperativity 23

Summary 24

3 A CELL–MOLECULAR STRATEGY FOR SOLVING THE EVOLUTIONARY PUZZLE 25

Rationale for Cell–Molecular Evolution 25

Mechanism of Mammalian Lung Development 28

Avian Lung Structure–Function Relationship: The Exception that Proves the Rule 32

Does Ontogeny Recapitulate Phylogeny? The Role of PTHrP in Lung Development 32

Interrelationship between PTHrP, Development, Physiology, and Repair: Is Repair a Recapitulation of Ontogeny and Phylogeny? 33

4 THE EVOLUTION OF CELL–CELL COMMUNICATION 35

Cell–Cell Communication as the Mechanistic Basis for Evolutionary Biology 36

The Darwinian Biologic Spacetime Continuum and Einstein’s Vision of the Universe 37

Reverse Engineering of Physiologic Traits as a Portal for Viewing Evolution 38

Cell–Cell Communication as the Basis for the Evolution of Metazoans 41

Understanding Lung Evolution from the Middle Out 42

The Cell–Cell Communication Model of Lung Evolution Traces Contemporary Phenotypes Back to Ancestral Phenotypes 43

Predictive Value of the Lung Cell–Cell Communication Model for Understanding the Evolution of Physiologic Systems 44

Sexual Dimorphism of Lung Development: A Case Study in Cell–Cell Communication and Evolutionary Plasticity 46

Androgen Affects the Expression of Growth Factors Involved in Lung Development 48

Evidence for an Association between Steroid-Resistant/Responsive Phenotypes and Human Lymphocyte Antigen (HLA) Haplotypes 49

5 HOW TO INTEGRATE CELL-MOLECULAR DEVELOPMENT, HOMEOSTASIS, ECOLOGY, AND EVOLUTIONARY BIOLOGY: THE MISSING LINKS 53

Neutral Theory versus Intelligent Design 54

Internal Selection Theory 54

The Counterintuitive Nature of Physiology and Solution to the Dead Sea Scrolls Puzzle 57

The Continuum from Microevolution to Macroevolution 58

cis Regulation and Adaptive Evolution 69

Evolution of cis Regulatory Mechanisms 70

6 FROM CELL–CELL COMMUNICATION TO THE EVOLUTION OF INTEGRATED PHYSIOLOGY 75

Cell–cell Signaling and Alveolar Development: A Reductionist Approach to the Evolution of Physiologic Traits 77

An Integrated, Empiric, Middle–Out Approach to Physiology 79

A Molecular Evolutionary Link between the Lung and the Kidney? 82

The Berner Hypothesis and Emergence of the Adipocyte: The Evolutionary Origins of the Lipofi broblast 83

Lung Biology as a Cipher for Evolution 85

Do Stretch Effects on PTHrP Expression Reflect Its Role in Adapting to Gravity? 85

Wolff’s Law Works for Both Bone and Lung 88

Functional Relationship between the External and Internal Environments 89

An Evolutionary Vertical Integration of the Phylogeny and Ontogeny of the Thyroid 91

7 EXPLOITING CELL–CELL COMMUNICATION ACROSS SPACETIME TO DECONSTRUCT EVOLUTION 95

Somewhere between the Gene and the Phenotype Lies the Process of Evolution 98

A Functional Genomic Approach to Evolution as an Example of Terminal Addition 100

Seeking Deep Homologies in Lung Evolution 102

Systems Biology Based on Cell–Cell Communication 105

Vertical Integration of Leptin Signaling, Human Evolution, and the Trojan Horse Effect 108

Leptin and Human Evolution: Food for Thought 109

8 THE PERIODIC TABLE OF BIOLOGY 115

The Prospect of a Periodic Table of Biology 115

Cellular Cooperation Is Key 116

Elemental Biology 118

PTHrP as an Archetype 118

Evolution as the Solution 119

Ramping Up a Mathematical Model of Evolution 121

The Anthropic Principle Results from the Evolution of Cell–Cell Interactions 124

9 VALUE ADDED BY THINKING IN TERMS OF THE CELL–CELL COMMUNICATION MODEL FOR EVOLUTION 125

This is Not a Just-So Story 126

Beyond Genomics 128

From Fat Cells to Integrated Physiology 128

Molecular Homologies Distinguish between the Evolutionary Forest and Trees 129

The Oxygen–Cholesterol–Surfactant–Membrane Connection 130

Cholesterol Metabolism as the Data Operating System for Vertebrate Biology? 131

Translation of Genomics into the Periodic Table for Biology 132

Deep Homologies 134

Selection Pressure for Cell–Cell Communication: The Key to Understanding Evolution 135

10 CELL–CELL COMMUNICATION AS THE BASIS FOR PRACTICING CLINICAL MEDICINE 139

Cell–Cell Communication Maintenance and Breakdown Represent Heath and Disease, Respectively 140

Cell–Cell Communications as a Framework for Human Evolution 140

Canalization, Decanalization, and the Holistic Approach to the Practice of Medicine 141

Exploiting Lung Evolution to Prevent and Treat Chronic Lung Disease 141

Lung Evolution Explains the Magic of Continuous Positive Airway Pressure 142

The Paradox of Infecting the Lung in Order to Treat Lung Disease Caused by Infection 143

Exploiting Lung Evolution to Prevent and Treat Smoking-Related Lung Damage 144

The Trojan Horse Effect of Canalization 145

Impetus for Evolutionary Science as an Integral Part of the Clinical Curriculum 146

Application of Evolutionary Science to Bioethics 147

Evolutionary Science, a Biologic Periodic Table, and a Unifi ed Theory of Biology 148

Summary 149

Name Index 151

Subject Index 153

V.K. Rehan, MD, is Professor of Pediatrics and Director of the Neonatal Intensive Care Unit at Harbor-UCLA Medical Center.  The recipient of numerous teaching honors, Dr. Rehan is involved both in treating patients and continuing research on neo and peri-natal respiratory issues and lung development.