What is the nature of the genetic changes underlying phenotypic evolution? We have catalogued 1008 alleles described in the literature that cause phenotypic differences among animals, plants, and yeasts. Surprisingly, evolution of similar traits in distinct lineages often involves mutations in the same gene (“gene reuse”). This compilation yields three important qualitative implications about repeated evolution. First, the apparent evolution of similar traits by gene reuse can be traced back to two alternatives, either several independent causative mutations or a single original mutational event followed by sorting processes. Second, hotspots of evolution—defined as the repeated occurrence of de novo mutations at orthologous loci and causing similar phenotypic variation—are omnipresent in the literature with more than 100 examples covering various levels of analysis, including numerous gain-of-function events. Finally, several alleles of large effect have been shown to result from the aggregation of multiple small-effect mutations at the same hotspot locus, thus reconciling micromutationist theories of adaptation with the empirical observation of large-effect variants. Although data heterogeneity and experimental biases prevented us from extracting quantitative trends, our synthesis highlights the existence of genetic paths of least resistance leading to viable evolutionary change.

Heliconius butterfly wing pattern mimicry is driven by cis-regulatory variation of the optix gene.

Although animals display a rich variety of shapes and patterns, the genetic changes that explain how complex forms arise are still unclear. Here we take advantage of the extensive diversity ofHeliconiusbutterflies to identify a gene that causes adaptive variation of black wing patterns within and between species. Linkage mapping in two species groups, gene-expression analysis in seven species, and pharmacological treatments all indicate thatcis-regulatory evolution of theWntAligand underpins discrete changes in color pattern features across theHeliconiusgenus. These results illustrate how the direct modulation of morphogen sources can generate a wide array of unique morphologies, thus providing a link between natural genetic variation, pattern formation, and adaptation.