Smith Erin N, Kruglyak Leonid
Lewis-Sigler Institute for Integrative Genomics and Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey, United States of America.
PLoS Biol. 2008 Apr 15;6(4):e83. doi: 10.1371/journal.pbio.0060083.
The effects of genetic variants on phenotypic traits often depend on environmental and physiological conditions, but such gene-environment interactions are poorly understood. Recently developed approaches that treat transcript abundances of thousands of genes as quantitative traits offer the opportunity to broadly characterize the architecture of gene-environment interactions. We examined the genetic and molecular basis of variation in gene expression between two yeast strains (BY and RM) grown in two different conditions (glucose and ethanol as carbon sources). We observed that most transcripts vary by strain and condition, with 2,996, 3,448, and 2,037 transcripts showing significant strain, condition, and strain-condition interaction effects, respectively. We expression profiled over 100 segregants derived from a cross between BY and RM in both growth conditions, and identified 1,555 linkages for 1,382 transcripts that show significant gene-environment interaction. At the locus level, local linkages, which usually correspond to polymorphisms in cis-regulatory elements, tend to be more stable across conditions, such that they are more likely to show the same effect or the same direction of effect across conditions. Distant linkages, which usually correspond to polymorphisms influencing trans-acting factors, are more condition-dependent, and often show effects in different directions in the two conditions. We characterized a locus that influences expression of many growth-related transcripts, and showed that the majority of the variation is explained by polymorphism in the gene IRA2. The RM allele of IRA2 appears to inhibit Ras/PKA signaling more strongly than the BY allele, and has undergone a change in selective pressure. Our results provide a broad overview of the genetic architecture of gene-environment interactions, as well as a detailed molecular example, and lead to key insights into how the effects of different classes of regulatory variants are modulated by the environment. These observations will guide the design of studies aimed at understanding the genetic basis of complex traits.
基因变异对表型性状的影响通常取决于环境和生理条件，但这种基因 - 环境相互作用却鲜为人知。最近开发的将数千个基因的转录丰度视为数量性状的方法，为广泛描述基因 - 环境相互作用的结构提供了契机。我们研究了在两种不同条件（以葡萄糖和乙醇作为碳源）下生长的两种酵母菌株（BY和RM）之间基因表达变异的遗传和分子基础。我们观察到，大多数转录本在菌株和条件之间存在差异，分别有2996、3448和2037个转录本显示出显著的菌株、条件以及菌株 - 条件相互作用效应。我们对来自BY和RM杂交的100多个分离株在两种生长条件下进行了表达谱分析，并确定了1382个显示出显著基因 - 环境相互作用的转录本的1555个连锁关系。在基因座水平上，通常对应于顺式调控元件多态性的局部连锁在不同条件下往往更稳定，因此它们更有可能在不同条件下表现出相同的效应或相同的效应方向。通常对应于影响反式作用因子多态性的远距离连锁则更依赖于条件，并且在两种条件下常常表现出不同方向的效应。我们鉴定了一个影响许多与生长相关转录本表达的基因座，并表明大部分变异是由IRA2基因中的多态性所解释的。IRA2的RM等位基因似乎比BY等位基因更强烈地抑制Ras/PKA信号传导，并且经历了选择压力的变化。我们的结果提供了基因 - 环境相互作用遗传结构的广泛概述，以及一个详细的分子实例，并对不同类型调控变异的效应如何受到环境调节产生了关键见解。这些观察结果将指导旨在理解复杂性状遗传基础的研究设计。
