Parallel molecular mechanisms for enzyme temperature adaptation

The mechanisms that underly the adaptation enzyme activities and stabilities to temperature are fundamental to our understanding of molecular evolution and how enzymes work. Herein, we investigate the molecular and evolutionary mechanisms of enzyme temperature adaption, combining deep mechanistic studies with comprehensive sequence analyses of thousands of enzymes. We show that temperature adaptation in ketosteroid isomerase (KSI) arises primarily from one residue change with limited, local epistasis and we establish the underlying physical mechanisms. This residue change occurs in diverse KSI backgrounds, suggesting parallel adaptation to temperature. We identify residues associated with organismal growth temperature in 1005 diverse bacterial enzyme families, suggesting widespread parallel adaptation. We assess the properties of these residues, molecular interactions and interaction networks that appear to underly temperature adaptation. Methods This Dryad data repository contains the starting datasets, analysis code and results (p-values and phylogenetic signals) for logistic regression models applied to 17,060,900 residue-positions in 2194 enzymes: Pinney, M.M, Mokhtari, D.A, Akiva, E., Yabukarski, F., Sanchez, D.M., Liang, R., Doukov, T., Martinez, T.J., Babbitt, P.C., Herschlag, D., Parallel Molecular Mechanisms for Enzyme Temperature Adaptation. See Pinney, et. al., for detailed Materials and Methods on how this dataset was collected and analyzed and for all associated references.