Idiosyncratic epistasis leads to global fitness-correlated trends

Epistasis can dramatically affect evolutionary trajectories. In recent decades, protein-level fitness landscapes have revealed extensive idiosyncratic epistasis among specific mutations. In contrast, other work has found ubiquitous and apparently non-specific patterns of global diminishing-returns and increasing-costs epistasis among mutations across the genome. Here, we use a hierarchical CRISPR gene drive system to construct all combinations of 10 missense mutations from across the genome in budding yeast, and measure 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 that has argued that fitness-correlated trends can emerge as the generic consequence of idiosyncratic epistasis.

上位性（epistasis）可显著影响演化轨迹。近数十年来，蛋白质水平适应度景观（protein-level fitness landscapes）领域的研究已揭示，特定突变间存在大量特异型上位性。与之相对，另有研究发现全基因组范围内的突变之间普遍存在非特异性的全局收益递减与成本递增型上位性模式。本研究借助分级CRISPR基因驱动系统（hierarchical CRISPR gene drive system），构建出酿酒酵母（budding yeast）全基因组范围内10个错义突变（missense mutations）的全部组合，并在六种环境中测定其适应度。研究结果表明，所得适应度景观呈现全局适应度相关趋势，但此类趋势实则源于特异型上位性互作。据此，本研究为近期相关理论研究提供了实验验证——后者提出，适应度相关趋势可作为特异型上位性的一般性结果出现。