Thermodynamic Origin of the Linear Pressure Dependence of DNA Thermal Stability

High pressure affects the structure and function of DNA and is a key parameter for studying the origin and physical limits of life. Different types of DNA structures systematically show a linear pressure dependence of thermal stability (up to ∼200 MPa), which is maintained even when the solution composition is changed. The reasons behind the linear pressure dependence are not understood. We have performed a thermodynamic analysis of the pressure-, temperature- and composition-dependent (un)­folding of various polynucleotide duplexes and G-quadruplexes. We demonstrate that the reason for the observed linearity is the link between compressibility and expansibility, both of which largely depend on DNA hydration. We predicted the temperature and pressure dependence of compressibility and expansibility of (un)­folding and explain how they affect the corresponding volume change and thermodynamic stability parameters. These predictions indicate the existence of a convergence temperature at which compressibility and volume of (un)­folding simultaneously become equal to zero.