Structural Robustness Confers Evolvability in Proteins

Theory suggests that biological robustness allows for the maintenance of fitness in the face of mutational change, and to the extent that this mutational change translates to heritable phenotypic change, that biological robustness allows for evolvability. However, empirical demonstrations that robustness promotes evolvability remain scant. This is in part due to the difficulty of defining and measuring both evolvability and robustness in real biological systems. Here we test whether protein structural robustness is associated with the extent of adaptive change a protein experiences. We find this to be the case for two forms of protein robustness—designability and modularity, which we measure via contact density and helix/sheet density, respectively. We interpret this association to be primarily the result of reduced constraints on amino acid substitutions in highly designable and/or modular proteins, resulting in less antagonistic pleiotropy and faster adaptation through natural selection.