Global Epistasis Makes Adaptation Predictable Despite Sequence-Level Stochasticity

摘要: Epistatic interactions between mutations can make evolutionary trajectories contingent on the chance occurrence of initial mutations. We used experimental evolution in Saccharomyces cerevisiae to quantify this contingency, finding differences adaptability among 64 closely related genotypes. Despite these differences, sequencing 104 evolved clones showed that genotype did not constrain future mutational trajectories. Instead, reconstructed combinations revealed a pattern diminishing-returns epistasis: Beneficial have consistently smaller effects fitter backgrounds. Taken together, results show beneficial affecting variety biological processes are globally coupled; they interact strongly, but only through their combined effect fitness. As consequence, fitness follows predictable trajectory even though sequence-level adaptation is stochastic.