For almost a century, our understanding of evolution has been based on the modern evolutionary synthesis, also known as “neo-Darwinism.” This paradigm assumes that natural selection is acting solely on the amount and structuring of heritable genetic variation, for which the ultimate origin is random mutation. Accordingly, genetic uniformity will severely constrain the adaptive flexibility of a given population or species, sooner or later resulting in evolutionary failure.

During the 1990s, a challenge to this foundation was posed: several studies revealed that heritable phenotypic variation did not need to be based on variation in primary (coding) DNA sequences; instead, novel permutations of spatial and temporal patterns of gene expression could be achieved via a suite of noncoding changes, even in the complete absence of genetic variability.