Robustness and evolvability in transcriptional regulation

The relationship between genotype and phenotype is central to our understanding of development, evolution, and disease. This relationship is known as the genotype- phenotype map. Gene regulatory circuits occupy a central position in this map, because they control when, where, and to what extent genes are expressed, and thus drive fundamental physiological, developmental, and behavioral processes in living organisms as different as bacteria and humans. Mutations that affect these gene expression patterns are often implicated in disease, so it is important that gene regulatory circuits are robust to mutation. Such mutations can also bring forth beneficial phenotypic variation that embodies or leads to evolutionary adaptations or innovations. Here we review recent theoretical and experimental work that sheds light on the robustness and evolvability of gene regulatory circuits.