A primary goal of evolutionary biology is to identify the genetic basis of phenotypic evolution. Early efforts often focused on the role of mutations in genes that encode structural proteins because these were the genomic elements most accessible at the time. Regulatory elements such as enhancers and promoters can also accumulate mutations with enormous effect on phenotypic evolution by altering the timing, amount or location of gene expression. However, it is difficult to identify these elements — let alone predict their functions — on the basis of sequence, which makes tying specific regulatory changes to evolved phenotypes a continued challenge. Against this backdrop, a thorough investigation by Chan et al. in 2010 showed how enhancer mutations drive phenotypic adaptation in sticklebacks, becoming an instant classic in the field as a testament to the role of regulatory changes in phenotypic evolution.

The authors focused on three-spined stickleback fish (Gasterosteus aculeatus), which have long been a model of scientific study for the impressive morphological variation observed throughout their range. Their three dorsal spines give the species its name, but most marine populations also feature a robust pelvic girdle that can be locked in an erect position, making the fish challenging for a predator to swallow. However, some stickleback populations have ventured from ocean to freshwater habitats where pelvic spines are no longer useful. In over two dozen cases, these stickleback populations experienced repeated pelvic spine reduction or loss, supporting the age-old adage, ‘use it or lose it’. Chan et al. sought to uncover the precise underlying molecular mechanisms contributing to these spine reductions.