Environment-independent distribution of mutational effects emerges from microscopic epistasis

A study aimed at uncovering patterns of microscopic and macroscopic epistasis in yeast Saccharomyces cerevisiae in variable environments. Paper abstract draft: Predicting how new mutations alter phenotypes is difficult because mutational effects vary across genotypes and environments. Recent studies found that the effects of many mutations on fitness scale with the fitness of the background genotype, but how the environment modulates this scaling is unknown. We measured the fitness effects of ~100 insertion mutations in 42 strains of Saccharomyces cerevisiae in six laboratory environments. We found that the environment does not alter the background-fitness scaling but tunes one global parameter, the background fitness at which most mutations switch sign. As a result, the distribution of mutational effects is remarkably predictable across genotypes and environments. This apparent simplicity points to some underlying physiological constraints that remain to be discovered.

本研究旨在揭示可变环境下酿酒酵母（Saccharomyces cerevisiae）微观上位性与宏观上位性的作用模式。论文摘要草稿如下：预测新突变如何改变表型颇具挑战，因为突变效应会随遗传背景与环境的变化而波动。近期研究表明，多数突变对适合度的影响会随遗传背景的适合度水平发生缩放，但环境如何调控这一缩放关系目前仍未知。我们在6种实验室环境中，对42株酿酒酵母的约100个插入突变的适合度效应进行了测定。研究发现，环境并不会改变遗传背景适合度的缩放关系，而是会调节一个全局参数——即大多数突变效应发生符号转换时的背景适合度水平。据此，突变效应的分布在不同遗传背景与环境下均呈现出显著的可预测性。这一表观上的简洁性暗示了尚未被发掘的潜在生理约束机制。