小效应尺寸突变对酵母数量性状的广泛累积影响。
Widespread Cumulative Influence of Small Effect Size Mutations on Yeast Quantitative Traits.
机构信息
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Systems Biology Graduate Program, Harvard University, Cambridge, MA, USA.
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
出版信息
Cell Syst. 2018 Dec 26;7(6):590-600.e6. doi: 10.1016/j.cels.2018.11.004.
Quantitative traits are influenced by pathways that have traditionally been defined through genes that have a large loss- or gain-of-function effect. However, in theory, a large number of small effect size genes could cumulatively play a substantial role in pathway function. Here, we determine the number, strength, and identity of all non-essential test genes that affect two quantitative galactose-responsive traits in addition to re-analyzing two previously screened quantitative traits. We find that over a quarter of assayed genes have a detectable, quantitative effect on phenotype. Despite their ubiquity, these genes are enriched in core cellular processes in a trait-specific manner. In a simulated population with 50% frequency of all-or-none alleles, we show that small effect size alleles are capable of contributing more to trait variation than alleles in a canonical, large effect size pathway. In total, by demonstrating that the genes effecting quantitative traits can be highly distributed and interconnected, this work challenges the concept of pathways as modular and independent.
数量性状受途径的影响，这些途径传统上是通过具有较大功能丧失或获得效应的基因来定义的。然而，从理论上讲，大量具有小效应量的基因可能会累积地在途径功能中发挥重要作用。在这里，我们确定了除重新分析两个以前筛选过的定量性状外，影响两个定量半乳糖响应性状的所有非必需测试基因的数量、强度和身份。我们发现，超过四分之一的被测试基因对表型具有可检测的定量影响。尽管它们无处不在，但这些基因以特定于性状的方式富集在核心细胞过程中。在一个具有 50%全有或全无等位基因频率的模拟群体中，我们表明，小效应量等位基因比经典的、大效应量途径中的等位基因更能导致性状变异。总的来说，通过证明影响定量性状的基因可以高度分布和相互关联，这项工作挑战了途径作为模块化和独立的概念。
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