List of Illustrations

Preface

1. What Is "Gene Sharing"?

New Functions for Old Proteins and the Question of Gene Duplication

Origin of the Term "Gene Sharing"

Gene Sharing: General Definition and Implications

Protein Location and Gene Regulation

Why the Term "Gene Sharing"?

Mechanisms for Diversifying Gene Functions

Posttranslational Modifications

Conditions for Initiating Gene Sharing

Contrasting Phenotype with Protein Function

Take-Home Message

2. Multifunctions and Functional Shifts: Echos from the Past

Preadaptation, Prospective Adaptation, and Hopeful Monsters

Quirky Functional Shifts and Exaptation

Spandrels and Gene Sharing

Gene Regulation and Tinkering

Take-Home Message

3. The Elusive Concept of a "Gene"

The Classical Gene Concept

The Mendel-Morgan Chromosomal Theory of the Gene

Later Developments: One Gene/One Enzyme/One Polypeptide

The Molecular Era of the Gene: So Much Data, So Many Possibilities

Quantifying Genes before the Molecular Era

Quantifying Genes in the Molecular Era: Fewer than Expected

Noncoding Regulatory Genes

Protein Diversity

The Ambiguous Gene

The "Molecular Gene" Concept

The "Molecular Process Gene" Concept

The "Evolutionary Gene" Concept

Two Concepts for One Gene: Gene-P/Gene-D

Gene Sharing: A Concept Incorporating an "Open Gene"

Take-Home Message

4. Eyes and Lenses: Gene Sharing by Crystallins

Eye Diversity: Many Forms to Perform a Function

The Lens

Crystallins and the Optical Properties of the Lens

Diversity and Taxon-Specificity of Lens Crystallins

Crystallins Are Borrowed Proteins

The bg-Crystallins: A Superfamily with Distant Stress Connections

The Enzyme-Crystallins of Vertebrates

Crystallins of Invertebrates

Crystallin Gene Regulation in Vertebrates: A Similar Cast of Transcription Factors

Convergent Evolution of Crystallin Gene Expression

Evolutionary Dynamism of shsp/aB-Crystallin Gene Expression

Convergent Evolution of Invertebrate and Vertebrate Crystallin Promoters

Potential for Lens-Specific Promoter Activity

Convergent Evolution and Relaxed Stringency for Crystallins

Take-Home Message

5. The Enigmatic "Corneal Crystallins": Putative Cases of Gene Sharing

The Cornea

Aldehyde Dehydrogenase: A Candidate Corneal Crystallin

Other Candidate Corneal Crystallins: Transketolase, Isocitrate Dehydrogenase, and Cyclophilin

Adseverin: A Corneal Crystallin in Zebrafish

A Signaling Role for Adseverin

Corneal Gene Expression

The Refracton Hypothesis: Implications for Gene Sharing

Take-Home Message

6. Gene Sharing As a Common Event: Many Multifunctional Proteins

Glycolytic Enzymes and the Versatile Hexokinases

Citrate Synthase: An Enzyme and a Cytoskeletal Structure

Lactate Dehydrogenase: An Enzyme for All Seasons

Regulation of mRNA Translation by Enzyme Binding

Glyceraldehye-3-phosphate Dehydrogenase: Constant Surprises

Enolase: Another Versatile Protein

Bacterial Surface Enzymes

Xanthine Oxidoreductase: Enzyme and Envelope

The Thioredoxin/Ribonucleotide Reductase System and Thioredoxin Family Members: From Redox to Morphogenesis

Serum Albumin: Transport Protein, Enzymatic Vasodilator and Detoxifier

Gelsolin: Roles in Cytoskeletal Structure, Gene Expression, Cell Death, and Signal Transduction

Cytochrome c: Roles in Electron Transport, Cell Death, and Light Filtration

Take-Home Message

7. Gene Sharing during Gene Expression

Complexity of Transcription

Nuclear Receptors

Metabolic Enzymes and Gene Expression

Y-Box Proteins

Transcription Factors as Translational Regulators: Bicoid

Translation Factors for RNA Export: eIF4

Homeoproteins, Chromosomal Proteins and Actin

The Dynamic Flux of Nuclear Proteins

Take-Home Message

8. Gene Sharing As a Dynamic Evolutionary Process: Antifreeze Proteins and Hemoglobins

Antifreeze Proteins

Hemoglobins

Take-Home Message

9. Gene Duplication and the Evolution of New Functions

Gene Duplication and Retention of Redundant Genes

Birth and Death of Duplicated Genes

Adaptive Evolution by Positive Selection: New Functions after Gene Duplication

Subfunctionalization and Gene Sharing

Rapid Subfunctionalization with Slow Neofunctionalization

Gene Sharing Is Independent of Gene Duplication

Lens Crystallins: Gene Sharing at Different Stages of Duplication

Take-Home Message

10. Gene Sharing and Systems Biology: Implications and Speculations

Networks

Evolvability

Selective Pressure Affecting Gene Regulation

Functional Switching and the Notion of Functional "Trespassing"

Functional Noise

Genetic Differences in Levels of Gene Expression

The Molecular Clock

Gene Knockout Experiments

Gene Deletion of b-Catenin

Horizontal Gene Transfer

Take-Home Message

11. Recapitulations: Ambiguities and Possibilities

Ambiguity of Cause and Effect

Natural Selection Versus Random Drift

Gene Sharing and Robustness: When Is a Mutation Neutral?

Inconsistency with Design

Naming Is Not Knowing

The Question of Tissue Homology

Phylogenetic Trees: The Complication of Function

Defining and Counting Genes

Definition of Polypeptide Function: The Ambiguity of Molecular Mechanism

Between Genotype and Phenotype

Gene Sharing and the Importance of Research on Diverse Species

Medical Implications

Glossary

References

Index

Joram Piatigorsky is a molecular biologist in Bethesda, Maryland.