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？两个进化机制有助于性状变异的人口，虽然他们的相对重要性仍然不清楚。反复出现的有害变异提供了有害等位基因的持续流入，这些等位基因通过纯化选择逐渐去除。此外，平衡选择可以保持由于有利的表型的多态性。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生物的变异具有重要意义。这些问题将解决使用克隆的数量性状位点（QTL）内的一个良好的特点在模式植物Boechera stricta的途径。该系统提供了已知的分子机制，并且可以在未受干扰的种群和未受干扰的栖息地中测量适合度，从而能够在历史相关环境中测试进化假设。这些分析结合了联合收割机在生物化学和调节功能方面的遗传变异、自然界中抗性性状和适合度的测量以及功能等位基因的地理和历史。这些旨在理解复杂性状变异的进化意义的实验必须面对QTL计划的局限性：可以发现的大效应等位基因可能不代表对进化有影响的基因。这项研究超越了这一限制。从影响防御化学和个体适应性的大效应多态性开始，已经确定了多个小效应功能等位基因差异。拟议的实验将精确量化等位基因对防御化学和基因表达的影响，并将测量这种变化在自然界中的后果，以了解自然选择在空间和时间上的变化。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.