Global epistasis makes adaptation predictable despite sequence-level stochasticity

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Science  27 Jun 2014:
Vol. 344, Issue 6191, pp. 1519-1522
DOI: 10.1126/science.1250939

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Clouding evolution's crystal ball

Because of a sort of mutation buffering process, different starting mutations can tend to end up with similar overall affects on an organism's fitness. Kryazhimskiy et al. evolved lines of yeast, each originating from distinct single genotypes, under the same selective regimen. A subset of clones from these adapted populations was subjected to fitness assays and sequenced. Populations with lower initial fitness, adapted more rapidly than populations with higher initial fitness, so that in the end the fitness levels were similar.

Science, this issue p. 1519


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.

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