Characterizing the landscape of evolvability

Abstract

A framework to experimentally traverse the large space of functionally neutral variants in a toxin–antitoxin protein complex reveals insights on evolvability and entrenchment of molecular interactions.

Fig. 1 |. Mutational analysis of toxin–antitoxin binding.

a–c, A series of deep mutational scanning experiments, along with high-throughput growth assays and modelling, were used to identify antitoxin variants that disrupt function (a); toxin variants that preserve toxicity and binding (b), and a combination of mutants that rescue disrupted binding in the antitoxin background (c). Many of these toxin compensatory mutants did not directly interact at the interface and were recognized by multiple antitoxin variants. Protein structures rendered with Protein Imager.