Epistasis and predictability of adaptation

Populations adapt to their environment by accumulating beneficial mutations, but predicting evolutionary outcomes is difficult because the effects of new mutations are contingent on prior mutations. We carried out an evolution experiment in budding yeast that quantifies this contingency. We evolved 10 populations starting from each of 64 founder strains that previously accumulated a small number of mutations. Sequencing of the evolved clones revealed that each population took a unique mutational trajectory towards higher fitness. Despite this diversity at the genetic level, different founders adapted at highly predictable rates that were determined by their initial fitness. We found that this remarkable predictability of fitness trajectories despite randomness at the sequence level occurs because the effects of new mutations on fitness depend only on the fitness of the strain in which they occur, but not on the specific prior mutations in that strain. Thus, while it may be impossible to predict which specific mutations a population will acquire during evolution, epistasis can channel the corresponding phenotypic changes towards a limited number of outcomes and thereby make phenotypic evolution predictable.