The gradual modification of transcription circuits over evolutionary time scales is an important source of the diversity of life. Over the past decade, studies in animals have shown how seemingly small molecular changes in gene regulation can have large effects on morphology and physiology and how selective pressures can act on these changes. More recently, genome-wide studies, particularly those in single-cell yeasts, have uncovered evidence of extensive transcriptional rewiring, indicating that even closely related organisms regulate their genes using markedly different circuitries.