Epigenetics in all its beauty

View Large Image | Download PowerPoint SlideDuring the past decade, the terms ‘epigenetics’ or ‘epigenetic’ have assumed an exceedingly narrow meaning, essentially only referring to the covalent modifications of either the DNA, histones or other components of the chromatin. When Waddington coined the term, he had a much wider meaning in mind, essentially covering all the causal processes producing the phenotype, except the immediate processes of gene expression [1xThe Strategy of the Genes. Waddington, C.H. See all References[1]. This definition includes all the cell–cell interactions that happen in development as well as the well-known tissue- and organ-level process, such as the influence of muscle pull on the shape of bones, or the influence of blood flow on blood vessel growth. It also included influences of environmental factors. This idea played an important role in the early devo-evo (or, more usually, evo-devo) movement, before the molecular genetic revolution in developmental biology.It is important to mention that epigenetic concepts were not meant to signify an anti-genetic viewpoint, but rather to emphasize that genetic causation can be very indirect and can act through long and tangled causal webs. The intention of Epigenetics. Linking Genotype and Phenotype in Development and Evolution, edited by Benedikt Hallgrimsson and Brian Hall, is to restore the idea of epigenetics to its original breadth and scope. The book contains papers from a historian of science, developmental biologists, anthropologists, population geneticists and evolutionary biologists to pull together the various strands of research and thinking that once had been called ‘epigenetic’, including the more recent developments (i.e. DNA and histone modification).The book has 23 chapters and it would not be meaningful to try to summarize each of them or even a significant subset of them here. Instead, I would like to use the content of the book to answer the fundamental question raised by this work: what would be lost if the original perspective of epigenetics was lost to science. In particular, I am interested in what the role of this concept is in evolutionary biology.To understand the role that the concept of epigenetics played in the early days of the evo-devo movement, it is useful to remember the even deeper historical roots of the term and idea. Epigenesis was the idea that, during development, the various parts of the organisms are built anew, rather than being preformed in some way in the germ cells. The important point here is that epigenesis was conceived in opposition to preformist ideas about development.Of course, ever since the 19th century, biologists did not have to battle the old form of preformism. With the rise of genetics during the 20th century, however, a new form of quasi-preformism arose, basically replacing the old homunculus with the genome, whereas the developmental process creating the phenotype was put in a black box. For much of biology, and in particular population genetics, this black boxing of development was not problematic, because variation and heritability could be explained by differences in the allelic composition of the genotype. However, there was a crack in the armor of this theoretical edifice, namely cases where the heritable factors could be demonstrated to have a very indirect relationship to the phenotype. An example is mammalian coat patterns. In mammals, one often finds systematic pigmentation differences between the legs and the body, for instance white legs and a black or brown body. The explanation of this phenotype is not genes for white legs but an interaction between temperature requirements of the enzymes producing the pigment and the fact that the body of a mammal tends to be warmer than its extremities. Here, simple physics, rather than specific genes, intrudes into the explanation of the phenotype.The same limit of the genetic model from the mid-20th century became obvious when research turned to the explanation of evolutionary novelties. The question was, if a new body part arises in evolution, say a sesamoid bone, then one has no homolog in ancestral generations; therefore, how then can there be a gene ‘for’ that new character when it was not there before? Of course the answer is that there is no gene for the new trait; instead, there are genes controlling the developmental process and, under certain conditions, this process crosses a threshold and leads to novel phenotypic elements, say a bone or a pigment spot. This way of thinking led to the side-effect hypothesis for the origin of evolutionary novelties [2xDevelopmental mechanisms at the origin on morphological novelty: a side-effect hypothesis. Muller, G.B. : 99–130See all References[2], which was an early concept of evolutionary developmental biology that still holds currency today.In these situations, it is important to remember that developmental processes are real physical processes that follow rules that are not explicitly prescribed in the genome. The phenotype is the result of the interaction between genes, their gene products and the environment. As such, epigenetics contributes not only to a more complete understanding of development, but also a broader view of how evolutionary outcomes are produced. Epigenetics, thus, is a conceptual signpost that ought not to be forgotten as long as we strive to understand how organisms work and how they originated through mutation, selection, drift and the interaction with the environment and the other parts of their own bodies. I hope that this book will teach students and researchers to remember the tangled web of causality that lies between the genotype and the phenotype, and to be inspired to research its intricacies as well as its broad implications for a deep understanding of life.