In his 1957 book entitled The Strategy of the Genes, British scientist Conrad Hal Waddington noted that the genetic sequence does not map directly onto the phenotype we can observe in nature. Contrary to the gene-centric views held by many of his contemporaries, Waddington emphasised that phenotypes ultimately depend on the interaction between genes and an array of often environment-sensitive developmental factors he labelled as ‘epigenetic’.1,[*] Using Waddington’s famous ‘epigenetic landscape’ metaphor, the process that connects genotype to phenotype can be described as travelling downhill through a series of valleys from a starting point at the top of the landscape. Some valleys are deep and narrow, which means that the ultimate phenotype will be robustly produced across a wide range of rearing environments. In other cases, the directing landscape is flat and can lead to a variety of end points (i.e. different phenotypes) because the development of a trait is sensitive to environmental influences, often mediated by epigenetic factors.2 Waddington went on to propose that epigenetic factors could play a role in evolution, by allowing organisms to adjust to environmental conditions. Such adaptive phenotypes are subsequently stabilised through selection on genetic variation,3 a hypothesis now known as ‘plasticity-first’ evolution.4
