Molecular ensembles make evolution unpredictable.

ABSTRACT: Evolutionary prediction is of deep practical and philosophical importance. Here we show, using a simple computational protein model, that protein evolution remains unpredictable, even if one knows the effects of all mutations in an ancestral protein background. We performed a virtual deep mutational scan-revealing the individual and pairwise epistatic effects of every mutation to our model protein-and then used this information to predict evolutionary trajectories. Our predictions were poor. This is a consequence of statistical thermodynamics. Proteins exist as ensembles of similar conformations. The effect of a mutation depends on the relative probabilities of conformations in the ensemble, which in turn, depend on the exact amino acid sequence of the protein. Accumulating substitutions a

SUBMITTER: Sailer ZR 

PROVIDER: S-EPMC5691298 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature