Genetic Mapping of MAPK-Mediated Complex Traits Across S. cerevisiae

Signaling pathways enable cells to sense and respond to their environment. Many cellular signaling strategies are conserved from fungi to humans, yet their activity and phenotypic consequences can vary extensively among individuals within a species. A systematic assessment of the impact of naturally occurring genetic variation on signaling pathways remains to be conducted. In S. cerevisiae, both response and resistance to stressors that activate signaling pathways differ between diverse isolates. Here, we present a quantitative trait locus (QTL) mapping approach that enables us to identify genetic variants underlying such phenotypic differences across the genetic and phenotypic diversity of S. cerevisiae. Using a Round-robin cross between twelve diverse strains, we identified QTL that influence phenotypes critically dependent on MAPK signaling cascades. Genetic variants under these QTL fall within MAPK signaling networks themselves as well as other interconnected signaling pathways. Finally, we demonstrate how the mapping results from multiple strain background can be leveraged to narrow the search space of causal genetic variants.

信号通路使得细胞能够感知并对其环境做出反应。众多细胞信号传导策略从真菌至人类均得以保留，然而，其活性和表型后果在同一物种个体间的差异却极为显著。对自然发生的遗传变异对信号通路影响的系统性评估尚待进行。在酿酒酵母（S. cerevisiae）中，对激活信号通路的应激源的响应和抵抗性在不同分离株之间存在差异。在此，我们提出了一种定量性状位点（QTL）定位方法，该方法使我们能够识别出在酿酒酵母遗传和表型多样性中导致此类表型差异的遗传变异。通过十二个不同菌株之间的循环互交，我们识别出影响依赖于MAPK信号级联的表型的QTL。这些QTL所包含的遗传变异既存在于MAPK信号网络之中，亦存在于其他相互连接的信号通路之中。最终，我们展示了如何利用来自多个菌株背景的映射结果来缩小因果遗传变异的搜索空间。