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Epigenetics: Linking Genotype and Phenotype in Development and Evolution

Benedikt Hallgrímsson
Brian k. Hall
Copyright Date: 2011
Edition: 1
Pages: 472
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  • Book Info
    Book Description:

    Illuminating the processes and patterns that link genotype to phenotype, epigenetics seeks to explain features, characters, and developmental mechanisms that can only be understood in terms of interactions that arise above the level of the gene. With chapters written by leading authorities, this volume offers a broad integrative survey of epigenetics. Approaching this complex subject from a variety of perspectives, it presents a broad, historically grounded view that demonstrates the utility of this approach for understanding complex biological systems in development, disease, and evolution. Chapters cover such topics as morphogenesis and organ formation, conceptual foundations, and cell differentiation, and together demonstrate that the integration of epigenetics into mainstream developmental biology is essential for answering fundamental questions about how phenotypic traits are produced.

    eISBN: 978-0-520-94882-2
    Subjects: Ecology & Evolutionary Biology

Table of Contents

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  1. Front Matter
    (pp. i-iv)
  2. Table of Contents
    (pp. v-vi)
    (pp. vii-viii)
  4. 1 Introduction
    (pp. 1-6)
    Benedikt Hallgrímsson and Brian K. Hall

    Epigeneticsis the study of emergent properties in the origin of the phenotype in development and in modification of phenotypes in evolution. Features, characters, and developmental mechanisms and processes are epigenetic if they can be understood only in terms of interactions that arise above the level of the gene as a sequence of DNA. Methylation and imprinting of gene sequences are examples of epigenetics at the level of the structure and function of the gene, sometimes referred to as the “phenotype” of the gene, a concept that blurs (appropriately, we believe) the distinction between genotype and phenotype established over 100...

  5. Part I Historical and Philosophical Foundations

    • 2 A Brief History of the Term and concept Epigenetics
      (pp. 9-13)
      Brian K. Hall

      This chapter provides a brief evaluation of the history of epigenetics as a term and as a concept. Although the term was not coined until the 1940s, the concept that genes are influenced by factors beyond the genome (the “epi” inepigenetics) is much older and can be traced to late nineteenth-century discussions of whether the nucleus or the cytoplasm “controlled” development, to earlier nineteenth-century discussions of whether the sperm or egg provided the primary material for development and therefore for life, and even earlier to the eighteenthcentury concepts of organismal structure as either preformed and arising by unfolding—the...

    • 3 Heuristic Reductionism and the Relative Significance of Epigenetic Inheritance in Evolution
      (pp. 14-40)
      James Griesemer

      The role of epigenetic inheritance in evolution is hotly contested. Some claim that recently discovered epigenetic mechanisms of gene regulation constitute a nongenetic inheritance system that underwrites a “Lamarckian dimension” of inheritance and therefore of evolution. Others judge epigenetic inheritance to be relatively insignificant in evolution, even in principle, due to disanalogies with the genetic system (unstable states, high mutation rates, non-Mendelian, Lamarckian). I argue for a role for relative significance arguments and reductionism in heuristic strategies for investment in epigenetics research. I argue that “biologists argue the way they do” (Beatty, 1997) because of differing goals and commitments of...

  6. Part II Approaches to Epigenetics

      (pp. 43-69)
      Lori A. McEachern and Vett Lloyd

      Genomic imprintingis an epigenetic process in which an allele is marked according to the sex of the parent transmitting it. These sex-specific marks may affect single genes, gene clusters, or entire chromosomes and result in maternal and paternal alleles or chromosomes that are epigenetically distinct from one another. This difference in epigenetic status can lead to differential transcriptional activity, chromosome loss, or chromosome inactivation. In an organism, allelic differences that result from genomic imprinting can be observed as the exclusive or preferential expression of a gene when it is inherited from one parent but not the other. Thus, in...

    • 5 Methylation Mapping in Humans
      (pp. 70-86)
      Christoph Grunau

      The importance of DNA methylation mapping in humans was rapidly recognized once it became apparent that 5-methylcytosine (5mC) is not only an exotic and negligible modification of the DNA but an important carrier of epigenetic information. In particular the finding that cancer is characterized by aberrant methylation increased the interest of the scientific community. Many laboratories attempted to characterize these changes in methylation and to use them as biomarkers for the diagnosis of disease. It had been known since the 1950s (Wyatt, 1951) that human DNA contains 5mC (later determined to be roughly 1%), and the initial experiments of Vanyushin...

    • 6 Asexuality and epigenetic variation
      (pp. 87-102)
      Root Gorelick, Manfred Laubichler and Rachel Massicotte

      Epigenetic processes are of fundamental importance for all living organisms as an individual phenotype is shaped by both its genome and its epigenome (Richards, 2006; Bossdorf et al., 2008). Byepigenetic, we mean all molecular signals that are literally on top of DNA, such as cytosine methylation, chromatin marks, histone modification, and RNAi (Allis et al., 2007), many of which are responsible for classical developmental processes, as seen by embryologists. Collectively, we refer to all of these molecular lecular epigenetic signals as theepigenome(Suzuki and Bird, 2008). Like Holliday and Pugh (1975), we consider these molecular epigenetic signals to...

    • 7 Epigenesis, Preformation, and the Humpty Dumpty Problem
      (pp. 103-115)
      Ellen W. Larsen and Joel Atallah

      Humpty Dumpty, of nursery rhyme fame, was an egg that fell off a wall and “all the King’s horses and all the King’s men, couldn’t put Humpty together again.” If we think of an incubated fertilized hen’s egg maintained under proper conditions of temperature, humidity, and egg rolling, a chick will develop in a few weeks. Try the same thing with a lightly scrambled egg, and . . . ? Why, when all the material, including the genome, exists in the bowl, do we not expect a downy hatchling to develop? To understand why embryo content alone is insufficient for...

    • 8 A Principle of Developmental Inertia
      (pp. 116-134)
      Alessandro Minelli

      Biology has long suffered from comparison with physics—biology is largely concerned with the description of historically determined phenomena, rather than with eternal laws. Recently, however, the status of biology has increased substantially, largely because of its success in studying genes and their expression and because of the widely appreciated importance of life sciences for the welfare of humanity and to safeguard our living space on Earth.

      To some extent, progress in the life sciences has involved technical, rather than conceptual, improvements in the way we study life phenomena. We are still largely confronted with experimental results obtained from a...

  7. Part III Epigenetics of Vertebrate Organ Development

    • 9 The Role of Epigenetics in Nervous System Development
      (pp. 137-163)
      Chris Kovach, Pierre Mattar and Carol Schuurmans

      A fundamental question is how cells acquire their specific identities and functional properties during embryogenesis. The intricate molecular controls that guide progression from pluripotent stem cells, which make up the early embryo, to a differentiated cell with a unique identity have begun to be elucidated (Figure 9.1). They include extrinsic signals, such as secreted or transmembrane signaling molecules, as well as intrinsic cues within cells, primarily transcription factors. It is currently well established that transcription factors play essential roles in cell fate specification, acting as key regulators of most, if not all, developmental programs in both invertebrates and vertebrates. However,...

    • 10 Morphogenesis of Pigment Patterns: EXPERIMENTAL AND MODELING APPROACHES
      (pp. 164-180)
      Lennart Olsson

      we intuitively think that the flock must be ruled by some overarching principle that governs the behavior of the birds. This is wrong, however, as are so many of our intuitions about natural phenomena. If we could understand nature just by everyday observations, science would be easy and all natural phenomena already properly explained. Instead, complex emergent phenomena in particular are counterintuitive, and Lewis Wolpert (2000) has pointed to the “unnatural nature of science” as a major reason that it has developed so late in human history and that it is difficult.

      The type of phenomenon exemplified by the flock...

    • 11 Epigenetic Interactions of the Cardiac Neural Crest
      (pp. 181-194)
      Martha Alonzo, Kathleen K. Smith and Margaret l. Kirby

      Epigenetic interactions as envisioned by Waddington involved animal, tissue, or cell responses to environmental cues such as hormones, cell–cell interactions, and mechanical and electrical forces. These mechanisms shape the “landscape” a cell travels through to reach its final differentiated state. In the case of neural crest cells, which migrate from their origin in the dorsal neural tube to distant target sites, there is a signaling landscape in addition to a changing geographic landscape. The signaling landscape includes both received signals and emitted signals. To fully appreciate the epigenetic interactions of the cardiac neural crest, it is first important to...

    • 12 Epigenetics in Bone and Cartilage Development
      (pp. 195-220)
      Tamara A. Franz-Odendaal

      This chapter describes the epigenetic processes involved in bone and cartilage development (osteogenesis and chondrogenesis, respectively). As defined earlier in this book, features, characters, or developmental processes are epigenetic if they can be understood only in terms of interactions that occur above the gene level. While the mapping of genomes is expanding at a great pace, our understanding of how gene networks result in morphological distinction or phenotypic variation is lagging behind. Understanding the epigenetic factors involved in skeletal (bone and cartilage) development includes understanding how epithelial and mesenchymal tissues interact; how positional signals, for example, are interpreted by cells;...

    • 13 Muscle–Bone Interactions and the Development of Skeletal Phenotype: JAW MUSCLES AND THE SKULL
      (pp. 221-237)
      Susan W. Herring

      The association between the musculature and the skeleton is both physiological and physical. Cell origins for the two tissues are not identical. For example, the cranial neural crest forms much of the skull but contributes only connective tissue to the muscles (Noden and Trainor, 2005). Nevertheless, muscular and skeletal cells go through a common mesenchymal stage of differentiation. Muscles and bones are also linked by genes and hormones which affect both tissues. Muscles and bones are attached to each other and jointly share the responsibility for support and movement of body parts.

      The most fundamental aspect of the interaction between...

    • 14 Evolution of the Apical Ectoderm in The Developing Vertebrate Limb
      (pp. 238-255)
      Lisa Noelle Cooper, Brooke Autumn Armfield and J. G. M. Thewissen

      Vertebrate limbs display a diverse array of morphologies, including the fins of teleosts and lungfish, wings of birds and bats, arms of humans, and flippers of cetaceans. Due to this morphological diversity, limbs are a topic of intense study in paleontology, phylogenetic systematics, descriptive embryology, and functional morphology. Evolutionary developmental biology (evo–devo) in particular has focused on understanding the developmental pathways that establish diverse limb phenotypes by integrating data from gene-expression and proteinsignaling with transplantation and ablation experiments. As a result of the increase in the number of evo–devo studies on diverse taxa, additional variants in the limb...

    • 15 Role of Skeletal Muscle in the Epigenetic Shaping of Organs, Tissues, and Cell Fate Choices
      (pp. 256-268)

      Since the inception of my independent laboratory in July 2000, I have been able to study the role of muscle in the shaping of developing tissues, which is an important example of Waddington epigenetics. This has been the focus of my research program. Muscle tissue is one of the four basic tissue types of which the body consists. There are three types of muscle tissue, and we are interested in one of them, the skeletal or striated muscle. We can study the developmental role of muscle in the whole mouse embryo or fetus because it is enough to knock out...

  8. Part IV Epigenetics in Evolution and Disease

    • 16 Epigenetic Integration, Complexity, and Evolvability of the Head: RETHINKING THE FUNCTIONAL MATRIX HYPOTHESIS
      (pp. 271-289)
      Daniel E. Lieberman

      As I get older, I find myself increasingly hesitant to use the wordepigeneticsbecause I worry about employing a term that is so liable to engender confusion and disagreement. Many biologists defineepigeneticsin a narrow sense solely as heritable changes in the phenotype that derive from molecular mechanisms other than sequence changes in the genotype (the classic example being methylation). However, Waddington, who coined the word in 1942, and other early users of the term had a broader concept in mind, one that captured the variable effects of interactions between genes, embryonic development, and the environment. According to...

      (pp. 290-316)
      Miriam Leah Zelditch and Donald L. Swiderski

      Epigenetic interactions are obviously necessary for normal development—without them there would be no primary embryonic induction, no epithelial–mesenchymal interactions, and no interactions between differentiated tissues such as muscles and bones. These interactions are necessary not only for normal development but also for normal function, if only because they produce the structures that carry out function. The ability of jawed vertebrates to eat typically requires having a jaw, and without epithelial–mesenchymal interactions there would be no jaw. However, eating requires more than just having a jaw, and epigenetic interactions do more than just produce it. Epigenetic interactions also...

    • 18 Epigenetic Contributions to Adaptive Radiation: INSIGHTS FROM THREESPINE STICKLEBACK
      (pp. 317-336)
      Susan A. Foster and Matthew A. Wund

      Phenotypic plasticityis variation in trait expression caused by influences of the environment on the expression of the phenotype. Plasticity can buffer organisms against the exigencies of environmental variation, enhancing fitness and facilitating the persistence of populations in novel environments (e.g., Baldwin, 1902; Schlichting and Pigliucci, 1998). In many contexts, texts, phenotypic plasticity is unquestionably adaptive; and like other aspects of phenotype, plasticity can evolve (Scheiner, 1993; Schlichting and Pigliucci, 1998; Pigliucci, 2005, for reviews). What is less clear is how phenotypic plasticity influences evolution. On the one hand, it could shield the genome from selection, slowing genetic responses to...

    • 19 Learning, Developmental Plasticity, and the Rate of Morphological Evolution
      (pp. 337-356)
      Christopher J. Neufeld and A. Richard Palmer

      Much has been written about how learning—the developmental plasticity of behavior—and morphological plasticity—the developmental plasticity of form—may individually affect the rate of morphological evolution (reviewed in Maynard Smith, 1987; Pigliucci, 2001; Weber and Depew, 2003; West-Eberhard, 2003). Surprisingly, rather little has been said explicitly about how these two kinds of plastic responses might amplify one another. Learning increases the frequency of certain behaviors as a result of past experience. Increased frequency of a behavior may, in turn, yield developmentally plastic responses in morphology. Finally, behaviors are continually modified via learning, in response to the suitability of...

    • 20 Epigenetics: Adaptation or Contingency?
      (pp. 357-376)
      Thomas F. Hansen

      Living organisms are enormously complex. Through development, the complex phenotype is built by cells using the genetic information encoded in some billions of base pairs of genome. This process is amazingly accurate. Excluding extrinsic mortality, most fertilized eggs are converted into normal functional adults of the requisite type. The conversion from genotype to phenotype requires accurate orchestration of numerous events on different hierarchical scales, from molecular interactions that control gene expression through the production of intracellular structures and metabolism, generation of cell-specific morphology and behavior, organization of tissues, orchestration of coordinated growth, and induction of tissues on different distances up...

    • 21 The Epigenetics of Dysmorphology: CRANIOSYNOSTOSIS AS AN EXAMPLE
      (pp. 377-397)
      Christopher J. Percival and Joan T. Richtsmeier

      Important discoveries in the field of evolutionary developmental biology have added significantly to our understanding of the evolution of developmental processes and the production of novel phenotypes, thereby advancing our knowledge of the molecular bases of genetic disease. This is especially true in the field of craniofacial biology, where anomalies of the head and neck account for 75% of all congenital birth defects (Chai and Maxson, 2006). Advances in the understanding of craniofacial dysmorphogenesis have come from varying approaches. Perhaps the most successful approach over the past 20 years has been the genetic mapping of diseases using human samples followed...

    • 22 Epigenetics of Human Disease
      (pp. 398-423)
      Peter D. Gluckman, Mark A. Hanson, Alan S. Beedle, Tatjana Buklijas and Felicia M. Low

      Research into the ways in which vulnerability to chronic noncommunicable disease in humans is governed by patterns of gene expression determined by molecular epigenetic marks established during development in large part follows from, and is closely linked to, the growing interest in the “developmental origins of health and disease” (DOHaD). Historically, development played a limited role in medical thought on the causation of human disease. This has dramatically changed in the last two decades, with the accumulation of epidemiological and animal experimental data pointing to early life as a critical period when much of future susceptibility to disease is established....

    • 23 Epigenetics: The Context of Development
      (pp. 424-438)

      The termepigeneticswas coined by Conrad Hal Waddington in 1957 as a merger ofepigenesiswithgenetics. Waddington (1957) defined epigenetics as the causal control of development or the causal control of gene action, without reference to specific mechanisms. As implied by the prefix epi, his intent was to convey mechanisms acting above the gene level. His metaphor of the epigenetic landscape provided a framework for conceptualizing how such mechanisms operate to bridge genotype and phenotype. At the time, the molecular basis for genetics and development ment was very poorly understood. For this reason, Waddington’s original concept of epigenetics...

  9. INDEX
    (pp. 439-459)
  10. Back Matter
    (pp. 460-460)