In the Light of Directed Evolution: Pathways of Adaptive Protein Evolution

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Prevalence of Epistasis in the Evolution of Influenza A Surface Proteins (2011, background): “Yet, numerous studies of protein evolution in vitro [27–29] as well as studies in bacteria [30] and viruses [20,31,32] have shown that beneficial mutations are often pleiotropic: in addition to their original beneficial effect, they cause some, usually negative, side effects on other protein propert”
Deep mutational scanning: assessing protein function on a massive scale (2011, background): “Furthermore, mutations that stabilize the folded structure of a protein can have powerful positive epistatic interactions with other adaptive mutations [53].”
Probing the Mutational Interplay between Primary and Promiscuous Protein Functions: A Computational-Experimental Approach (2012, background): “Protein promiscuity has been extensively studied in recent years due to its important biotechnological applications [6–12], to its role in adaptive metabolic plasticity [13–15] and also because of its fundamental connection with molecular evolution.”