title: Microbial evolution. Global epistasis makes adaptation predictable despite sequence-level stochasticity.
abstract: 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 in adaptability among 64 closely related genotypes. Despite these differences, sequencing of 104 evolved clones showed that initial genotype did not constrain future mutational trajectories. Instead, reconstructed combinations of mutations revealed a pattern of diminishing-returns epistasis: Beneficial mutations have consistently smaller effects in fitter backgrounds. Taken together, these results show that beneficial mutations affecting a variety of biological processes are globally coupled; they interact strongly, but only through their combined effect on fitness. As a consequence, fitness evolution follows a predictable trajectory even though sequence-level adaptation is stochastic.
authors: Department of Organismic and Evolutionary Biology, Harvard University, Cambridge MA 02138.|FAS Center for Systems Biology, Harvard University, Cambridge MA 02138.
authors: Sergey
authors: S
authors: Kryazhimskiy
authors: Department of Organismic and Evolutionary Biology, Harvard University, Cambridge MA 02138.|FAS Center for Systems Biology, Harvard University, Cambridge MA 02138.
authors: Daniel P
authors: DP
authors: Rice
authors: Department of Physics, Harvard University, Cambridge MA 02138.|FAS Center for Systems Biology, Harvard University, Cambridge MA 02138.
authors: Elizabeth R
authors: ER
authors: Jerison
authors: Department of Organismic and Evolutionary Biology, Harvard University, Cambridge MA 02138.|Department of Physics, Harvard University, Cambridge MA 02138.|FAS Center for Systems Biology, Harvard University, Cambridge MA 02138.
authors: Michael M
authors: MM
authors: Desai
mesh_terms: D000222:Adaptation, Physiological; D001483:Base Sequence; D019020:Directed Molecular Evolution; D004843:Epistasis, Genetic; D019143:Evolution, Molecular; D005800:Genes, Fungal; D056084:Genetic Fitness; D016681:Genome, Fungal; D005838:Genotype; D008957:Models, Genetic; D058977:Molecular Sequence Annotation; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000502:physiology*; D017422:Sequence Analysis, DNA; D013269:Stochastic Processes