Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA.
Quantitative Biology Initiative, Harvard University, Cambridge, MA, USA.
Science. 2022 May 6;376(6593):630-635. doi: 10.1126/science.abm4774. Epub 2022 May 5.
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.
上位性可显著影响进化轨迹。近几十年来，蛋白质水平的适应度景观揭示了特定突变之间广泛的特殊上位性。相比之下，其他研究发现，在整个基因组的突变中，存在普遍且明显非特异性的全局报酬递减和成本递增的上位性模式。在这里，我们使用分层的 CRISPR 基因驱动系统，在出芽酵母中构建了来自基因组的 10 个错义突变的所有组合，并在六个环境中测量了它们的适应性。我们表明，由此产生的适应度景观表现出全局适应性相关的趋势，但这些趋势是由特定的特殊相互作用产生的。因此，我们为最近的理论工作提供了实验验证，该理论认为，与适应性相关的趋势可以作为特殊上位性的一般后果而出现。
