Introduction

Benedikt Hallgrímsson and Brian K. Hall

Epigenetics is 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 years ago. Inductive interactions between two cell populations that lead to the formation of a third are examples of epigenetic phenomena at the cell population level.

Aspects of bone morphology are epigenetic in origin because they arise as the result of interactions between muscle activity and bone. The result of those interactions is not predictable from the intrinsic development of either tissue but can be understood only at the level of their interaction. Interactions between individuals of the same or different species also are epigenetic, as seen in the adjustment of the number of soldiers in an ant colony in response to depletion of soldier numbers and to hormonal cues or in the interactions between predator and prey species in plankton, where diffusible chemicals from the predator elicit the formation of features in the prey not seen in the absence of the predator.

Epigenetics falls broadly within the area of systems biology premised on the concept that system-level phenomena are essential as explanatory factors in biology. Concepts such as epigenetics are required not because biological systems are fundamentally indeterminate but because their complexity prohibits the construction of an exhaustive deterministic framework. Epigenetic explanations arise whenever we create theoretical constructs to make sense of the complex relationships between genetic and phenotypic variation and evolution. In these senses, canalization, developmental stability, and integration are epigenetic phenomena. Developmental pathways, networks, and processes also are epigenetic concepts. Explanations of development and evolution that focus on properties of processes or pathways, such as the Atchley and Hall (1991) model for mandibular development or Salazar-Ciudad and Jernvall's (2005) interactome for tooth development, are epigenetic explanations. In both of these cases, the relevant parts of the explanations for phenotypic variation are at the level of the interactions among gene products, among cell populations, and among the processes generated that link the two levels.

Biological systems may or may not be completely deterministic above the level of subatomic particles. However, they are functionally indeterminate in the sense that their complexity prevents us in most cases from creating frameworks that predict phenotypic outcomes directly from DNA sequences or sequence variation. Epigenetics is the study of the construction of frameworks that allow us to bridge the gulf between genotype and phenotype and thus integrate the vast amount of information that is being generated about the roles of specific genes in developmental systems. Thus, epigenetics is more than the study of emergent properties in developmental systems. It defines an area of study and a level of processes that creates a coherent understanding of the emergent relationship between genotype and phenotype.

The term epigenetics has increased in use in the molecular, evolutionary, and developmental literature in recent years. Its varied use in evolutionary and developmental biology has made it meaningless to many. Our definition is very much in the spirit of Waddington's (1957) concept of the "epigenotype." We follow Hall (1990) and Salazar-Ciudad and Jernvall (2005) in defining epigenetics as the study of the epigenotype, which is the study of the properties of the pathways and processes that link the genotype and phenotype.

Molecular genetics, developmental biology, and, to a lesser degree, evolutionary developmental biology have deemphasized the study of epigenetics. This is due to technical...