Molecular Causes and Fitness Consequences of Complex Trait Variation

复杂性状变异的分子原因和适应性后果

基本信息

批准号：
8899587
负责人：
Storrs Thomas Mitchell-Olds
金额：
$ 29.78万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-30 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8899587
关键词：
Address Alleles Arabidopsis Biochemical Biochemistry Chemicals Chemistry Complex Data Diet Environment Equilibrium Evolution Frequencies Gene Expression Genes Genetic Genetic Polymorphism Genetic Variation Genetic screening method Genotype Geography Glucosinolates Habitats Health Heterogeneity Human Human Genetics Immigrant Immigration Individual Insecta Malignant Neoplasms Measurement Measures Methods Molecular Mutation Natural Selections Nature Nucleotides Organism Outcome Pathway Analysis Pathway interactions Pattern Performance Phenotype Plant Model Plants Pollen Population Population Genetics Population Heterogeneity Process Quantitative Trait Loci Recording of previous events Relative (related person)Research Resistance Risk Sampling Site Source Structure System Testing Time Transgenic Organisms Validation Variant fitness genome wide association study genome-wide improved migration novel programs research study spatial temporal variation trait

项目摘要

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.

描述（由申请人提供）：在人群和物种内维持遗传变异的进化因素的相对重要性是什么？尽管尚不清楚，两种进化机制导致人口的性状差异。反复出现的有害变体提供了持续的有害等位基因的涌入，这些等位基因通过纯化选择逐渐消除。此外，由于有利的表型，平衡选择可以维持多态性。了解这些替代方案的重要性对我们周围生物体的人类健康和变异的遗传学具有重要意义。这些问题将在模型植物Boechera Stricta中使用良好特征的途径中使用克隆的定量性状基因座（QTL）来解决。该系统提供了已知的分子机制，并且可以在不受干扰的人群和未受干扰的栖息地中测量适应性，从而可以在历史上相关环境中对进化假设进行检验。这些分析结合了生物化学和调节功能的遗传变异，自然界的抗性特征和适应性的测量以及功能等位基因的地理和历史。这样的实验要了解复杂性状变化的进化意义，必须面对QTL程序的局限性：可以发现的大效应等位基因可能对进化重要的基因而言无代表性。这项拟议的研究超出了这一限制。从影响自然界的防御性化学和个人适应性的大效应多态性开始，已经确定了多个小型功能等位基因差异。提出的实验将准确地量化对防御性化学和基因表达的等位基因影响，并将衡量这种自然界变异的后果，以了解时空中自然选择的变化。这些方法可以阐明进化因素的相对重要性，这些因素维持生态上重要特征的遗传变异。