An integrative view of the evolution of genetics and the natural
world

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.

John Torday, PhD, is Professor of Pediatrics and Ob/Gyn
at Harbor-UCLA Medical Center where he is also Director of The
Henry L. Guenther Laboratory for Cell/Molecular Research and
Director of Laboratory for Evolutionary Preventive Medicine.
He is the author of over 130 peer-reviewed articles, Dr. Torday
specializes in pre and neo-natal lung development, particularly
regarding cell-cell communication within this pathway.

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.

Even in this advanced age of genomics, the evolutionary process of unicellular and multicellular organisms is continually in debate. Evolutionary Biology, CellCell 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 CellCell Communication 7

The Endomembrane System 9

The Cellular Mechanism of Evolution 10

Why Evolve? 11

CellCell 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 CELLMOLECULAR STRATEGY FOR SOLVING THE EVOLUTIONARY PUZZLE 25

Rationale for CellMolecular Evolution 25

Mechanism of Mammalian Lung Development 28

Avian Lung StructureFunction 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 CELLCELL COMMUNICATION 35

CellCell 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

CellCell Communication as the Basis for the Evolution of Metazoans 41

Understanding Lung Evolution from the Middle Out 42

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

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

Sexual Dimorphism of Lung Development: A Case Study in CellCell 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 CELLCELL COMMUNICATION TO THE EVOLUTION OF INTEGRATED PHYSIOLOGY 75

Cellcell Signaling and Alveolar Development: A Reductionist Approach to the Evolution of Physiologic Traits 77

An Integrated, Empiric, MiddleOut 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 …