Genetic mapping of MAPK-mediated complex traits Across S. cerevisiae.
Genetic mapping of MAPK-mediated complex traits Across S. cerevisiae.
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DOI：
10.1371/journal.pgen.1004913
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发表时间：
2015-01
期刊：
影响因子：
4.5
通讯作者：
Kruglyak L
中科院分区：
文献类型：
--
作者：
Treusch S;Albert FW;Bloom JS;Kotenko IE;Kruglyak L
信号通路使细胞能够感知和响应环境。从真菌到人类，许多细胞信号传导策略是保守的，但它们的活性和表型结果在一个物种内的个体之间可能有很大差异。自然发生的遗传变异对信号通路的影响的系统评估仍有待进行。In S.酿酒酵母，无论是响应和抗性激活信号转导途径的压力不同菌株之间。在这里，我们提出了一个数量性状基因座（QTL）定位方法，使我们能够确定遗传变异的基础上，这种表型差异的遗传和表型多样性的S。啤酒。使用12个不同菌株之间的循环杂交，我们确定了影响表型的QTL，这些表型严重依赖于MAPK信号级联。这些QTL下的遗传变异属于MAPK信号网络本身以及其他相互连接的信号通路。最后，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。野生酵母菌株的表型不同，由高度保守的信号通路控制。然而，天然存在的遗传变异如何影响酵母中的信号通路仍然是未知的。我们已经开发了一种方法，以促进映射的遗传变异，这些表型差异的基础上，在一组野生菌株。我们的定位方法需要最小的应变工程，并使映射群体的快速隔离从任何应变背景。特别是，我们已经绘制了12个高度多样化的酵母菌株的遗传变异。此外，我们演示了如何从这12个菌株的映射结果可以联合使用，以缩小遗传变异的数量确定一组推定的因果变异。我们确定了在细胞信号传导中具有各种作用的基因的遗传变异。我们的研究结果说明了不同信号通路的相互作用，以及哪些信号基因更可能包含具有大表型影响的变体。
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. Wild yeast strains differ in phenotypes that are controlled by highly conserved signaling pathways. Yet it remains unknown how naturally occurring genetic variants influence signaling pathways in yeast. We have developed an approach to facilitate the mapping of genetic variants that underlie these phenotypic differences in a set of wild strain. Our mapping approach requires minimal strain engineering and enables the rapid isolation of mapping populations from any strain background. In particular, we have mapped genetic variants in twelve highly diverse yeast strains. Further, we demonstrate how the mapping results from these twelve strains can be used jointly to narrow the number of genetic variants identified to a set of putative causal variants. We identify genetic variants in genes with various roles in cell signaling. Our results illustrate the interplay of different signaling pathways and which signaling genes are more likely to contain variants of large phenotypic impact.
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影响因子：
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通讯作者：
Schiestl, Robert H.
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