Fuentes Valenzuela Lucas, Francois Paul, Skotheim Jan M
Department of Biology, Stanford University, Stanford, United States.
Department of Biochemistry and Molecular Medicine, University of Montreal, Montreal, Canada.
Elife. 2025 Sep 2;14:RP105265. doi: 10.7554/eLife.105265.
Genetic analyses, which examine the phenotypic effects of mutations both individually and in combination, have been fundamental to our understanding of cellular functions. Such analyses rely on a neutrality function that predicts the expected phenotype for double mutants based on the phenotypes of the two individual non-interacting mutations. In this study, we examine fitness, the most fundamental cellular phenotype, through an analysis of the extensive colony growth rate data available for budding yeast. Our results confirm that the Product neutrality function describes the colony growth rate, or fitness, of a double mutant as the product of the fitnesses of the individual single mutants. This Product neutrality function performs better than Additive or Minimum neutrality functions, supporting its continued use in genetic interaction studies. Furthermore, we explore the mechanistic origins of this neutrality function by analyzing two theoretical models of cell growth. We perform a computational genetic analysis to show that in both models, the Product neutrality function naturally emerges due to the interdependence of cellular processes that maximize growth rates. Thus, our findings provide mechanistic insight into how the Product neutrality function arises and affirm its utility in predicting genetic interactions affecting cell growth and proliferation.
基因分析通过单独和组合研究突变的表型效应，对于我们理解细胞功能至关重要。此类分析依赖于一种中性函数，该函数根据两个非相互作用的单个突变的表型来预测双突变体的预期表型。在本研究中，我们通过分析酿酒酵母广泛的菌落生长速率数据来研究适应性，这是最基本的细胞表型。我们的结果证实，乘积中性函数将双突变体的菌落生长速率或适应性描述为各个单突变体适应性的乘积。该乘积中性函数比加性或最小中性函数表现更好，支持其在遗传相互作用研究中的持续应用。此外，我们通过分析两种细胞生长的理论模型来探索这种中性函数的机制起源。我们进行了计算遗传分析，以表明在这两种模型中，由于最大化生长速率的细胞过程的相互依赖性，乘积中性函数自然出现。因此，我们的研究结果为乘积中性函数的产生提供了机制性见解，并肯定了其在预测影响细胞生长和增殖的遗传相互作用方面的效用。
