Data from: 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（signaling pathway）可使细胞感知并响应其所处环境。诸多细胞信号传导策略在从真菌到人类的演化过程中均保守存在，但其活性与表型效应在同一物种的不同个体间却存在广泛差异。目前仍缺乏针对自然发生的遗传变异对信号通路影响的系统性评估。在酿酒酵母（Saccharomyces cerevisiae）中，对激活信号通路的各类应激源的响应与抗性在不同分离株间存在显著差异。本研究提出了一种数量性状位点（quantitative trait locus，QTL）定位方法，可在酿酒酵母的遗传与表型多样性背景下，鉴定出驱动此类表型差异的遗传变异。我们通过12株不同菌株间的循环杂交（round-robin cross），鉴定出了调控关键依赖于丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）信号级联反应的表型的QTL。这些QTL关联的遗传变异既存在于MAPK信号网络自身，也分布于其他相互关联的信号通路中。最后，我们展示了如何利用多菌株背景下的定位结果，缩小候选因果遗传变异的筛选范围。