美国哈佛大学Michael M. Desai研究团队发现异质上位性导致整体适应度相关趋势。该研究于2022年5月6日发表于国际一流学术期刊《科学》杂志上。

他们使用分层 CRISPR 基因驱动系统构建芽殖酵母基因组中 10 个错义突变的所有组合，并检测它们在六种环境中的适应度。他们表明，由此产生的适应性景观表现出整体适应相关的趋势，但这些趋势来自特定的特殊相互作用。因此，他们为最近的理论工作提供了实验验证，认为与适应度相关的趋势可以作为异质上位性的一般结果出现。

研究人员表示，上位性可以显著影响进化轨迹。 近几十年来，蛋白质水平的适应性景观揭示了特定突变之间广泛的异质上位性。相比之下，其他工作发现了在整个基因组突变之间普遍存在，且明显非特异性的整体收益递减和成本增加的上位性模式。

附：英文原文

Title: Idiosyncratic epistasis leads to global fitness–correlated trends

Author: Christopher W. Bakerlee, Alex N. Nguyen Ba, Yekaterina Shulgina, Jose I. Rojas Echenique, Michael M. Desai

Issue&Volume: 2022-05-06

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.

DOI: abm4774

Source: https://www.science.org/doi/10.1126/science.abm4774