Redundant and Cryptic Enhancer Activities of the Gene.

-regulatory sequences known as enhancers play a key role in regulating gene expression. Evolutionary changes in these DNA sequences contribute to phenotypic evolution. The gene, which is required for pigmentation, has emerged as a model system for understanding how -regulatory sequences evolve, providing some of the most detailed insights available into how activities of orthologous enhancers have diverged between species. Here, we examine the evolution of -regulatory sequences on a broader scale, by comparing the distribution and function of enhancer activities throughout the 5' intergenic and intronic sequences of , , and We find that -regulatory sequences driving expression in a particular tissue are not as modular as previously described, but rather have many redundant and cryptic enhancer activities distributed throughout the regions surveyed. Interestingly, cryptic enhancer activities of sequences from one species often drove patterns of expression observed in other species, suggesting that the frequent evolutionary changes in expression observed among species may be facilitated by gaining and losing repression of preexisting -regulatory sequences.