Molecular Mechanisms of Natural Variation in Arabidopsis

描述(由申请人提供)：这项建议解决了一个简单的问题：植物对环境的反应自然发生变化的分子机制是什么？在研究最深入的植物信号通路中，有那些调节环境光影响的信号通路，还有那些将光信息与其他变量相结合来控制开花的信号通路。尽管利用正向和反向遗传学以及功能基因组学工具进行了相当大的努力，但在涉及光信号和开花反应的基因方面，我们的知识仍然存在许多空白。因此，我们提出了一种遗传和基因组相结合的方法来鉴定不同自然菌株之间的差异基因，这些基因的差异导致了不同品系在光信号转导和开花反应上的差异。我们已经通过鉴定几个基因中自然产生的功能变异，证明了这类研究的可行性。此外，我们已经生成了大量资源，使拟议的研究成为可能。 具体地说，我们建议(1)识别控制光信号和开花的额外基因组区域；(2)精细定位和识别自然变异的基因；(3)对已识别的基因及其自然变异进行详细的机制分析；以及(4)对这些自然变异以及其他影响自然变异的候选基因进行物种范围的研究。 重要的是，我们还希望获得对光和开花反应的新的基本见解。为了支持这一断言，我们已经确定了两个影响幼苗对光的反应的基因组区域，但不包含任何从实验室突变实验中已知的控制这一过程的基因。我们有强有力的初步证据表明，至少有一个区域包含一个功能改变的等位基因，其对光调节发育的影响无法从受影响基因的敲除表型中预测出来。因此，这项拟议的工作将扩大我们对光和开花反应的机械知识，以及我们对A.thaliana中自然发生的遗传变异的理解。这些研究将为未来更大规模的调查奠定基础。

DESCRIPTION (provided by applicant): This proposal addresses a simple question: what are the molecular mechanisms that underlie naturally occurring variation in plant responses to the environment? Among the best-studied plant signaling pathways are those that mediate the effects of ambient light, along with those that integrate light information with other variables to control flowering. Despite considerable efforts using forward and reverse genetics as well as the tools of functional genomics, there remain many gaps in our knowledge of the genes involved in light signaling and flowering responses. Therefore, we propose a combination of genetic and genomic approaches to identify genes that vary between natural isolates of Arabidopsis thaliana, and whose variation leads to strain-specific differences in light signal transduction and flowering responses. We have already demonstrated the feasibility of such studies by identifying naturally occurring functional variants in several genes. In addition, we have generated a large set of resources that enable the proposed studies. Specifically, we propose to (1) identify additional genomic regions controlling light signaling and flowering; (2) fine-map and identify genes underlying natural variation; (3) perform detailed mechanistic analyses of the identified genes and their natural variants; and (4) to conduct species-wide studies of these natural variants as well as of other candidates affecting natural variation. Importantly, we also expect to gain new basic insights into light and flowering responses. In support of this assertion, we have already identified two genomic regions that affect a seedling's response to light, but do not contain any gene known from laboratory mutagenesis experiments to control this process. We have strong preliminary evidence that at least one of the regions contains a change-of-function allele whose effect on light-regulated development would not have been predicted from the knockout phenotype of the affected gene. The proposed work will thus expand both our mechanistic knowledge of light and flowering responses, and our understanding of naturally occurring genetic variation in A. thaliana. These studies will set the stage for future, larger-scale investigations.