A Genomic Analysis of Complex Trait Variation in Mimulus

描述(申请人提供)：大多数复杂的性状变异是由几个常见的等位基因引起的，还是很大程度上是由于许多稀有变异的综合作用？每个座位的等位基因对数量性状的影响有多大？效应大小是否与基因座上的等位基因频率相关？这些都是贯穿整个生物学的重要问题。突变-选择平衡预测多态基因座将具有稀有等位基因，而平衡选择模型预测中等等位基因频率。这些进化机制的各自贡献决定了站立变异与适应性进化的相关性，以及数量性状进化受到突变而不是选择的限制的程度。在人类健康中，所谓的常见病/常见变异假说就是对这些情况的陈述，其有效性具有明确的临床意义。拟议的研究推进了正在进行的实验，使用模式植物Mimulus guttatus，以提供对维持自然种群遗传变异的遗传和生态因素的严格探索。其目的是确定与健康相关的性状变异的序列水平决定因素。这项研究涉及古典和现代遗传学、分子生物学、统计建模和田间实验相结合。这项研究不仅应该确定自然选择是否保持了生态上重要特征的遗传变异，而且还应该开始阐明涉及的特定选择因素。第三个目标还开发了一种新的数量性状基因座群体定位方法，该方法可能适用于广泛的生物体。拟议的研究将在该项目的四年中每年培训本科生、博士生和博士后研究人员。

DESCRIPTION (provided by applicant): Is most complex trait variation caused by a few common alleles, or is it largely due to the aggregate contributions of many rare variants? How large are per-locus allelic effects on quantitative traits? Is effect size correlated with allele frequency across loci? These are questions of import throughout biology. Mutation- selection balance predicts that polymorphic loci will have rare alleles while balancing selection models predict intermediate allele frequencies. The respective contributions of these evolutionary mechanisms determines the relevance of standing variation to adaptive evolution and the extent to which quantitative trait evolution is limited by mutation as opposed to selection. In human health, the so-called common disease/common variant hypothesis is a statement on these conditions and its validity has clear clinical implications. The proposed studies advance ongoing experiments using the model plant Mimulus guttatus to provide a rigorous exploration of the genetic and ecological factors that maintain genetic variation in natural populations. The aims are to determine sequence-level determinants of variation in fitness-related traits. This research involves a combination of classical and modern genetics, molecular biology, statistical modeling, and field experimentation. The research should determine not only whether natural selection maintains genetic variation in ecologically important traits, but will begin to elucidate the particular selective agents that are involved. The third aim also develops a novel procedure for population mapping of quantitative trait loci that is potentially applicable to a broad range of organisms. The proposed studies will train undergraduates, doctoral students, and postdoctoral researchers in each of the four years of the project.