The rewiring of transcription circuits in evolution

Abstract

The binding of transcription regulators to cis-regulatory sequences is a key step through which all cells regulate expression of their genes. Due to gains and losses of cis-regulatory sequences and changes in the transcription regulators themselves, the binding connections between regulators and their target genes rapidly change over evolutionary time and constitute a major source of biological novelty. This review covers recent work, carried out in a wide range of species, that addresses the overall extent of these evolutionary changes, their consequences, and some of the molecular mechanisms that lie behind them.

Figure 1

Three common types of evolutionary changes that can alter transcription circuits: A. Gains and losses of cis-regulatory sequences by simple mutation. Because cis-regulatory sequences are typically short and can function from multiple positions with respect to a target gene, gains probably occur nearly as frequently as losses. B. The gain of a favorable protein-protein interaction can occur through a small number of point mutations. C. Through mutations in its “effector” domain, a transcription regulator can be converted from an activator to a repressor or vice versa.

Figure 2

Three handoffs of sets of metabolic genes from one transcriptional regulator to another occurred during fungal evolution [–26].

Figure 3

Circuit movement mediated by cooperative DNA binding. Although only a single target gene is shown, this proposed process, which begins with the evolution of a new protein-protein interaction, could lead to rewiring of a whole set of co-regulated genes. This scenario could also occur in more complex enhancers, where one regulator could substitute for another while other regulators bound to the enhancer remain unchanged. The cis-regulatory sequences indicated with diagonal bars represent low-affinity sequences that are present by chance.