Data from: Diminishing-returns epistasis among random beneficial mutations in a multicellular fungus

Adaptive evolution ultimately is fuelled by mutations generating novel genetic variation. Non-additivity of fitness effects of mutations (called epistasis) may affect the dynamics and repeatability of adaptation. However, understanding the importance and implications of epistasis is hampered by the observation of substantial variation in patterns of epistasis across empirical studies. Interestingly, some recent studies report increasingly smaller benefits of beneficial mutations once genotypes become better adapted (called diminishing-returns epistasis) in unicellular microbes and single genes. Here, we use Fisher's geometric model (FGM) to generate analytical predictions about the relationship between the effect size of mutations and the extent of epistasis. We then test these predictions using the multicellular fungus Aspergillus nidulans by generating a collection of 108 strains in either a poor or a rich nutrient environment that each carry a beneficial mutation and constructing pairwise combinations using sexual crosses. Our results support the predictions from FGM and indicate negative epistasis among beneficial mutations in both environments, which scale with mutational effect size. Hence, our findings show the importance of diminishing-returns epistasis among beneficial mutations also for a multicellular organism, and suggest that this pattern reflects a generic constraint operating at diverse levels of biological organization.

适应性进化最终由产生新遗传变异的突变所驱动。突变适合度效应的非加性（称为上位性（epistasis））可能会影响适应性的动力学过程与可重复性。然而，由于不同实证研究中上位性模式存在显著差异，我们对上位性的重要性与影响的理解仍受限于此。有趣的是，近期多项研究发现，当基因型的适应性水平提升后，有益突变带来的收益会逐渐减小，该现象被称为收益递减上位性（diminishing-returns epistasis），这一结论已在单细胞微生物与单基因研究中得到验证。本研究借助费希尔几何模型（Fisher's geometric model, FGM），推导得到关于突变效应大小与上位性程度之间关系的解析预测。随后，我们以多细胞真菌构巢曲霉（Aspergillus nidulans）为实验对象，开展验证工作：分别在贫瘠与丰富营养环境中构建108株携带单一位点有益突变的菌株，并通过有性杂交构建两两组合菌株。研究结果支持费希尔几何模型的预测，同时发现在两种营养环境中，有益突变间均存在负上位性，且该效应的强度随突变效应大小发生变化。综上，本研究表明有益突变间的收益递减上位性同样存在于多细胞生物中，且该模式反映了在生物组织不同层级普遍存在的一般性约束。