Estimating The Contribution Of Folding Stability To Non-Specific Epistasis In Protein Evolution

摘要: The extent of non-additive interaction among mutations or epistasis reflects the ruggedness fitness landscape, mapping genotype to reproductive fitness. In protein evolution, there is strong support for importance and prevalence epistasis, but whether a universal mechanism behind remains unknown. It also unclear which biophysical properties proteins, such as folding stability, activity, binding affinity, dynamics, have strongest contribution epistasis. Here, we determine selection stability in evolution. By combining theoretical estimates rates molecular evolution thermodynamics, show that simple implies at least ~30% ~60% amino acid substitutions would experienced Additionally, our model predicts substantial marginal stabilities therefore linking strength selection. Estimating governing factors will provide better understanding could improve methods