Gene-environment interaction in yeast gene expression.
Gene-environment interaction in yeast gene expression.
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DOI：
10.1371/journal.pbio.0060083
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发表时间：
2008-04-15
期刊：
影响因子：
9.8
通讯作者：
Kruglyak L
中科院分区：
文献类型：
--
作者：
Smith EN;Kruglyak L
遗传变异对表型性状的影响往往取决于环境和生理条件，但这种基因与环境的相互作用知之甚少。最近发展的方法将数千个基因的转录丰度视为数量性状，为广泛表征基因-环境相互作用的结构提供了机会。我们研究了两种酵母菌株（BY和RM）在两种不同条件下（葡萄糖和乙醇为碳源）基因表达差异的遗传和分子基础。我们观察到，大多数转录本因菌株和条件而异，分别有2,996、3,448和2,037个转录本表现出显著的菌株、条件和菌株条件相互作用效应。我们分析了在两种生长条件下由BY和RM杂交产生的100多个分离片段的表达谱，并鉴定了1,382个转录本的1,555个连锁，显示出显著的基因与环境相互作用。在基因座水平上，通常与顺式调控元件多态性相对应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果或相同的作用方向。远链通常对应于影响反式作用因子的多态性，它更依赖于条件，在两种条件下往往表现出不同方向的影响。我们描述了一个影响许多生长相关转录物表达的位点，并表明大多数变异是由基因IRA2的多态性解释的。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，并且经历了选择压力的变化。我们的研究结果提供了基因-环境相互作用的遗传结构的广泛概述，以及详细的分子示例，并导致对环境如何调节不同类别的调控变异体的影响的关键见解。这些观察结果将指导旨在理解复杂性状的遗传基础的研究设计。个体经常遇到不同的环境条件，对这些条件的生理和行为反应可能取决于个体的基因组成。这种现象被称为基因-环境相互作用。例如，感染了恶性疟原虫的个体容易感染疟疾，但如果他们携带血红蛋白的镰状细胞等位基因就不会。人们对基因-环境相互作用的一般特性了解甚少，如果个人要在其基因组信息的指导下做出明智的健康选择，更好的了解是必不可少的。我们在基因组水平上研究了基因-环境相互作用，通过研究酵母基因表达的自然变异，同时表征了它在4000多个性状中的作用。我们比较了实验室和葡萄园的酵母菌株在两种条件下（葡萄糖和乙醇作为碳源）生长，它们分别采用两种不同的代谢状态：发酵和有氧呼吸。我们表明基因-环境相互作用是一种普遍现象，描述了不同类型的遗传变异如何影响相互作用的性质，并提供了相互作用的详细分子例子。我们表明基因-环境相互作用是基因表达调控中的一种常见现象，我们描述了不同类型的遗传变异如何影响相互作用的性质，我们提供了相互作用的详细分子例子。
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. Individuals frequently encounter different environmental conditions, and the physiological and behavioral responses to these conditions can depend on an individual's genetic makeup. This phenomenon is known as gene–environment interaction. For example, individuals who are infected with the Plasmodium falciparum parasite are susceptible to malaria, but not if they carry the sickle-cell allele of hemoglobin. The general properties of gene–environment interaction are poorly understood, and a better understanding is essential if individuals are to make informed health choices guided by their genomic information. We have investigated gene–environment interaction on a genomic level, characterizing its role in over 4,000 traits at once by investigating natural variation in yeast gene expression. We compared lab and vineyard strains of yeast growing in two conditions (glucose and ethanol as carbon sources) in which they adopt two different metabolic states: fermentation and aerobic respiration, respectively. We show that gene–environment interaction is a common phenomenon, describe how different classes of genetic variants affect the nature of the interactions, and provide detailed molecular examples of interactions. We show that gene-environment interaction is a common phenomenon in the regulation of gene expression, we describe how different classes of genetic variants affect the nature of the interactions, and we provide detailed molecular examples of interactions.
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