Molecular Causes and Fitness Consequences of Complex Trait Variation

描述(由申请人提供)： 维持种群和物种内遗传变异的进化因素的相对重要性是什么？两种进化机制有助于种群中的性状变异，尽管它们的相对重要性尚不清楚。反复出现的有害变异提供了有害等位基因的持续涌入，这些有害等位基因通过净化选择逐渐被移除。此外，由于有利的表型，平衡选择可以保持多态。了解这些替代品的重要性对人类健康的遗传学和我们周围有机体的变异具有重要意义。这些问题将通过克隆的数量性状基因座(QTL)在模式植物严格牛角草(Boechera Structa)中得到解决。这个系统提供了已知的分子机制，可以在未受干扰的种群和未受干扰的生境中测量适合度，从而能够在历史相关的环境中测试进化假说。这些分析结合了生化和调节功能的遗传变异，抗性特征和自然界适合度的测量，以及功能等位基因的地理和历史。为了理解复杂性状变异的进化意义，这些实验必须面对QTL程序的限制：可以发现的大效应等位基因可能不能代表对进化至关重要的基因。这项拟议的研究突破了这一限制。从影响防御化学和个体健康的大效多态开始，已经确定了多个小效功能等位基因的差异。拟议的实验将精确地量化等位基因对防御化学和基因表达的影响，并将测量这种自然界变异的后果，以了解自然选择在空间和时间上的变异。这些方法可以阐明维持生态重要性状遗传变异的进化因素的相对重要性。

DESCRIPTION (provided by applicant): What is the relative importance of evolutionary factors that maintain genetic variation within populations and species? Two evolutionary mechanisms contribute to trait variation in populations, although their relative importance remains unclear. Recurring deleterious variants provide a continual influx of harmful alleles which are gradually removed by purifying selection. In addition, balancing selection can maintain polymorphisms due to advantageous phenotypes. Understanding the importance of these alternatives has important implications for the genetics of human health and variation in the organisms around us. These questions will be addressed using a cloned quantitative trait locus (QTL) within a well-characterized pathway in the model plant Boechera stricta. This system provides known molecular mechanisms, and fitness can be measured in undisturbed populations and undisturbed habitats, enabling tests of evolutionary hypotheses in historically relevant environments. These analyses combine genetic variation in biochemical and regulatory function, measurements of resistance traits and fitness in nature, and the geography and history of functional alleles. Such experiments to understand the evolutionary significance of complex trait variation must confront the limitations of the QTL program: the large-effect alleles that can be discovered may be unrepresentative of the genes that matter for evolution. This proposed research moves beyond this limitation. Beginning with a large-effect polymorphism that influences defensive chemistry and individual fitness in nature, multiple, small-effect functional allelic differences have been identified. The proposed experiments will quantify precisely the allelic effects on defensive chemistry and gene expression, and will measure the consequences of this variation in nature in order to understand variation of natural selection in space and time. These approaches can elucidate the relative importance of evolutionary factors that maintain genetic variation for ecologically important traits.