Global Epistasis Makes Adaptation Predictable Despite Sequence-Level Stochasticity

By Sergey Kryazhimskiy, D. P. Rice, Elizabeth R. Jerison, Michael M. Desai. 2014

454 citations recorded by the source corpus.

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 Epistasis makes fitness trajectories unpredictable in yeast, even as they converge upon the same biological pathway. 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.

Subfields: Genetics, Sociology and Political Science

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

In Sociology and Political Science

Citations in the corpus

Revealing evolutionary constraints on proteins through sequence analysis (2018, background): “This phenomenon is known as global [10,14] or nonspecific [9] epistasis, and its relevance has been shown in evolution experiments [14], over and above contributions from specific epistasis [9, 15].”
Epistasis and the Dynamics of Reversion in Molecular Evolution (2016, background): “…to increase, particularly in the case of diminishing-returns epistasis, where mutations that have strong positive effects early in adaptation have much smaller effects towards the end of adaption (Draghi and Plotkin 2013; Kryazhimskiy et al. 2014, c.f. Hartl et al. 1985; Hartl and Taubes 1996).”
Inferring the shape of global epistasis (2018, background): “Today, the idea that epistatic interactions are the result of a nonlinear mapping from an underlying additive trait has been called “unidimensional” (26, 27), “nonspecific” (28), or “global” (29) epistasis, and several heuristic techniques have been proposed to infer epistasis of this form (30–33).”
Inexpensive Multiplexed Library Preparation for Megabase-Sized Genomes (2015, unknown): “Sequencing has become an indispensible tool in modern microbiology, dramatically changing the resolution and speed of studies of biodiversity [1], evolution [2-6], and molecular biology [7], and improving pathogen surveillance [8] and clinical diagnostics [9,10].”
Predicting evolution (2017, background): “The emerging picture of smooth phenotype-fitness maps with ‘macroscopic’ epistasis 38 (Fig.”
Epistasis and Adaptation on Fitness Landscapes (2022, background): “Moreover, an increasing number of studies have followed evolutionary trajectories in the laboratory and dissected epistatic effects along those trajectories (e.g. Kryazhimskiy et al. 2014, Johnson et al. 2019).”