A Genomic Analysis of Complex Trait Variation in Mimulus

描述（由申请人提供）：大多数复杂的性状变异是由少数常见的等位基因引起的，还是很大程度上是由于许多罕见变异的共同贡献？每个基因座等位基因对数量性状的影响有多大？效应大小与基因座间等位基因频率相关吗？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位点将具有罕见的等位基因，而平衡选择模型预测中间等位基因的频率。这些进化机制各自的贡献决定了直立变异与适应性进化的相关性，以及数量性状进化在多大程度上受到突变而不是选择的限制。在人类健康,所谓的常见疾病/常见的变体的假设是这些条件及其有效性的声明有明确的临床意义。这些建议的研究推进了正在进行的使用模式植物Mimulus guttatus的实验，为维持自然种群遗传变异的遗传和生态因素提供了严格的探索。目的是确定序列水平的决定因素变异在健康相关的性状。这项研究涉及古典与现代遗传学、分子生物学、统计建模和现场实验的结合。这项研究不仅要确定自然选择是否维持了生态上重要性状的遗传变异，而且要开始阐明所涉及的特定选择因素。第三个目标还开发了一种新的程序，用于数量性状位点的群体定位，这可能适用于广泛的生物。拟议的研究将在项目的四年中每年培养本科生、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.