Experimental mapping of the joint sequence space of an ancient transcription factor (TF) and its DNA binding sites reveals that epistasis across the molecular interface permitted the evolution of a new and specific TF-DNA complex.
The acquisition of new foreign DNA by the prokaryotic adaptive immune system CRISPR-Cas is shown to depend on the fundamental sequence specificity of the Cas1 integrase.
The extra dimensions in protein sequence space open up indirect paths of adaptation and alleviate the constraint on the selective accessibility to high fitness genotypes.
The epistasis observed in TF-DNA binding preferences can be explained by the presence of two optima of very similar Gibbs energy that are located relatively far from each other in sequence space.