Rediscovering Waddington in the post-genomic age
Conrad Hal Waddington was a revolutionary interdisciplinary thinker well ahead of his time. Many of his ideas have been subsumed into our current understanding of developmental biology [1]. His pioneering theories, first published in the mid-20th century, continue to find validation 50 years later in the molecular era of developmental genetics [2]. Among his many contributions, Waddington [3] introduced the term epigenetics to describe the full variety of emergent developmental phenomena above the level of the genome, and elegantly expressed these ideas in the form of his widely recognised and explicitly evolutionary epigenetic landscape metaphor [3]. These emergent phenomena bridge the gap between genotype and phenotype, and comprise the epigenotype [5]. Because of this close relationship between development and evolution, it is important to grasp how such epigenetic mechanisms function. The diverse use of the term epigenetics in the subsequent literature has led to substantial disagreement about what exactly is being discussed, and at which level(s) of inquiry, despite several attempts to achieve consensus [6, 7]. In most contemporary biological contexts, epigenetics refers to chromatin modification [8]. Not only does Waddington’s more inclusive definition appear to have been largely abandoned, also the different uses of his term have coincided with the near disappearance of the original concept of epigenetics from models of evolutionary change [9]. We see this as a potentially significant problem for evolutionary biologists. In this essay our focus is on the theoretical concepts originally specified by Waddington’s epigenetics. We argue that, in this age of powerful postgenomic laboratory and bioinformatics tools, epigenetics sensu Waddington is more informative and instructive than it has been for decades. Waddington’s epigenetics has the potential to shed new light on the means by which both selectable variation and innovation, two key features of evolutionary theory, are