Abstract
The relationship between mutation, protein stability and protein function plays a central role in molecular evolution. Mutations tend to be destabilizing, including those that would confer novel functions such as host-switching or antibiotic resistance. Elevated temperature may play an important role in preadapting a protein for such novel functions by selecting for stabilizing mutations. In this study, we test the stability change conferred by single mutations that arise in a G4-like bacteriophage adapting to elevated temperature. The vast majority of these mutations map to interfaces between viral coat proteins, suggesting they affect protein-protein interactions. We assess their effects by estimating thermodynamic stability using molecular dynamic simulations and measuring kinetic stability using experimental decay assays. The results indicate that most, though not all, of the observed mutations are stabilizing.
Highlights
One of the overarching objectives of evolutionary biology is to understand what has happened in the past, why it occurred, and how it may be predictive of further evolution [1]
Proteins tend to exist in a range of folding stabilities (DG = -3 to -10 kcal/ mol) where, at equilibrium, the vast majority of molecules are in the folded state [2]
In this study we test the hypothesis that beneficial mutations that arise in a microbial population exposed to elevated temperature have stabilizing effects. We do this by assessing the stability of capsids for viral mutants that were obtained by adaptation under elevated temperature but without selection for any other novel function (Figure 1B)
Summary
One of the overarching objectives of evolutionary biology is to understand what has happened in the past, why it occurred, and how it may be predictive of further evolution [1]. Most mutations decrease the thermodynamic and kinetic folding stability of proteins. We do this by assessing the stability of capsids for viral mutants that were obtained by adaptation under elevated temperature but without selection for any other novel function (Figure 1B).
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