Treusch Sebastian, Albert Frank W, Bloom Joshua S, Kotenko Iulia E, Kruglyak Leonid
Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America.
Department of Human Genetics, University of California, Los Angeles, Los Angeles, California, United States of America.
PLoS Genet. 2015 Jan 8;11(1):e1004913. doi: 10.1371/journal.pgen.1004913. eCollection 2015 Jan.
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.
信号通路使细胞能够感知并响应其环境。许多细胞信号传导策略从真菌到人类都是保守的，然而它们的活性和表型后果在一个物种内的个体之间可能有很大差异。对自然发生的遗传变异对信号通路影响的系统评估仍有待进行。在酿酒酵母中，不同菌株对激活信号通路的应激源的反应和抗性存在差异。在这里，我们提出了一种数量性状基因座（QTL）定位方法，使我们能够在酿酒酵母的遗传和表型多样性中识别出导致此类表型差异的遗传变异。通过在十二个不同菌株之间进行循环杂交，我们确定了影响严重依赖MAPK信号级联反应的表型的QTL。这些QTL下的遗传变异位于MAPK信号网络本身以及其他相互连接的信号通路中。最后，我们展示了如何利用来自多个菌株背景的定位结果来缩小因果遗传变异的搜索空间。
