Tinkering with transcription factor proteins: the role of transcription factor adaptation in developmental evolution

Evolution of transcriptional regulation is often seen as being driven by the origin of transcription factor binding sites in cis-regulatory DNA. But there is strong evidence that transcriptional specificity of transcription factor proteins is determined by protein-protein interaction with other transcription factors. Here we summarize the evidence that transcription factor protein function itself is evolving and suggest that this might play an integral if not leading role in the evolution of gene regulation.