Cis- and trans-acting mutations contribute differently to gene expression evolution.

Cis-regulatory variants often have larger effects and alter expression of fewer genes.

Both coding and non-coding variants contribute to trans-regulatory variation.

Regulatory networks can diverge without gene expression divergence.

Transcription factor (TF) function evolves slower than TF binding sites.

Studies of regulatory variation in yeast — at the level of new mutations, polymorphisms within a species, and divergence between species — have provided great insight into the molecular and evolutionary processes responsible for the evolution of gene expression in eukaryotes. The increasing ease with which yeast genomes can be manipulated and expression quantified in a high-throughput manner has recently accelerated mechanistic studies of cis- and trans-regulatory variation at multiple evolutionary timescales. These studies have, for example, identified differences in the properties of cis- and trans-acting mutations that affect their evolutionary fate, experimentally characterized the molecular mechanisms through which cis- and trans-regulatory variants act, and illustrated how regulatory networks can diverge between species with or without changes in gene expression.

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