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Idiosyncratic epistasis leads to global fitness-correlated trends.

ABSTRACT: Epistasis can markedly affect evolutionary trajectories. In recent decades, protein-level fitness landscapes have revealed extensive idiosyncratic epistasis among specific mutations. By contrast, other work has found ubiquitous and apparently nonspecific patterns of global diminishing-returns and increasing-costs epistasis among mutations across the genome. Here, we used a hierarchical CRISPR gene drive system to construct all combinations of 10 missense mutations from across the genome in budding yeast and measured their fitness in six environments. We show that the resulting fitness landscapes exhibit global fitness-correlated trends but that these trends emerge from specific idiosyncratic interactions. We thus provide experimental validation of recent theoretical work arguing that fitness-correlated trends can emerge as the generic consequence of idiosyncratic epistasis.

SUBMITTER: Bakerlee CW

PROVIDER: S-EPMC10124986 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Idiosyncratic epistasis leads to global fitness-correlated trends.

Bakerlee Christopher W CW Nguyen Ba Alex N AN Shulgina Yekaterina Y Rojas Echenique Jose I JI Desai Michael M MM

Science (New York, N.Y.) 20220505 6593

Epistasis can markedly affect evolutionary trajectories. In recent decades, protein-level fitness landscapes have revealed extensive idiosyncratic epistasis among specific mutations. By contrast, other work has found ubiquitous and apparently nonspecific patterns of global diminishing-returns and increasing-costs epistasis among mutations across the genome. Here, we used a hierarchical CRISPR gene drive system to construct all combinations of 10 missense mutations from across the genome in buddi ...[more]

PMID: 35511982

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