Molecular causes and fitness consequences of complex trait variation

描述（由申请人提供）：尽管基因组学的最新进展已经揭示了大量的核苷酸多态性，但对基因为什么会分离影响数量性状的变体知之甚少。这项拟议的研究旨在确定哪些进化过程影响复杂性状的自然遗传变异。为了鉴定和解释潜在QTL的等位基因变体，该实验系统具有四个基本特征：1）生态上重要的复杂性状，2）已知途径中的可克隆QTL，3）可以测量适合度的不受干扰的环境，以及4）保留时间和地理历史的序列特征的不受干扰的群体。这些进化分析使用生物化学将基因型与表型联系起来，并使用自然环境来衡量适应性。然而，这项工作的基本理由是测试有关影响复杂性状变异的进化过程的假设。为了实现这一目标，将克隆一个影响生态重要性数量变异的QTL。具有优于单基因分辨率的近等基因系将用于测量在其自然环境中生长的功能相异等位基因的适合度和表型。最后，序列变异将被用来推断历史和进化的影响，在未受干扰的人口等位基因变异。公共卫生相关性：这项研究将有助于我们理解复杂的性状变异，这是人类疾病的主要原因之一。此外，这些实验还研究了芥子油苷的遗传学，芥子油苷是生物医学研究的焦点，因为它们在预防多种形式的癌症以及幽门螺杆菌引起的胃炎中发挥作用。

DESCRIPTION (provided by applicant): Although recent advances in genomics have revealed a tremendous amount of nucleotide polymorphism, little is known about why genes segregate for variants that influence quantitative traits. This proposed research seeks to determine which evolutionary processes influence natural genetic variation for complex traits. In order to identify and interpret allelic variants underlying QTLs, this experimental system has four fundamental characteristics: 1) An ecologically important complex trait, 2) a clonable QTL in a known pathway, 3) undisturbed environments where fitness can be measured, and 4) undisturbed populations which retain sequence signatures of temporal and geographic history. These evolutionary analyses use biochemistry to connect genotype with phenotype, and use natural environments to measure fitness. Nevertheless, the fundamental justification for this work is to test hypotheses regarding the evolutionary processes which influence complex trait variation. Towards this goal, a QTL will be cloned which influences ecologically important quantitative variation. Near isogenic lines with better than single gene resolution will be used to measure the fitness and phenotypes of functionally divergent alleles grown in their natural environments. Finally, sequence variation will be used to infer historical and evolutionary influences on allelic variation in undisturbed populations. Public Health Relevance: This proposed research will contribute to our understanding of complex trait variation, which is one of the primary causes of human disease. In addition, these experiments examine the genetics of glucosinolates, which are a focus of biomedical research due to their role in prevention of many forms of cancer, as well as gastritis attributable to Helicobacter pylori.