Genomic Diversity and the Architectures of Adaptation and Incompatibility

基因组多样性以及适应和不相容的架构

• 批准号: 10368935
• 负责人: JOHN E POOL
• 金额: $ 22.88万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10368935
• 关键词: Address; African; Architecture; Consequentialism; Disease; Drosophila genus; European; Evolution; Future; Generations; Genes; Genetic; Genetic Drift; Genetic Epistasis; Genetic Variation; Genetic study; Genome; Genomics; Heart Diseases; Immune; Individual; Infertility; Medical; Natural Selections; Penetrance; Performance; Population; Portraits; Process; Reproduction; Research; Role; Shapes; Signal Transduction; Spontaneous abortion; System; Time; Transgenic Organisms; Variant; Work; computer studies; cost effective; diabetes risk; disorder risk; experimental study; genetic architecture; genetic resource; genetic variant; genomic data; human disease; insect disease vector; novel strategies; programs; reproductive; scale up; tool; trait

Project Summary: Genomic Diversity and the Architectures of Adaptation and Incompatibility This research program addresses fundamental yet unresolved questions at the interface between genetic variation and evolutionary processes. In particular, it focuses on three interconnected research themes: (1) The Genetic Complexity of Adaptive Trait Evolution, (2) The Genetic Basis of Early Stage Reproductive Isolation, and (3) The Determinants of Genomic Diversity and Adaptive Potential. It fuses ambitious but cost-effective Drosophila experiments with novel approaches to the analysis of large genomic data sets. D. melanogaster offers critical advantages for this work. The global expansion of this species enables the study of adaptive trait differences, and partial reproductive isolation, between populations that diverged in the last ~10,000 years. Due to this recent time-scale, adaptive differences may be detected from genetic variation. The experimental efficiency of Drosophila allows the study of large lab populations across many generations. Its compact genome allows economical sequencing. Once relevant genes are found, functional confirmation and study are aided by a well-annotated genome and a wealth of genetic resources and transgenic tools. This research will bolster understanding of The Genetic Complexity of Adaptive Trait Evolution. Initial findings have suggested a portrait of adaptation that often begins with standing genetic variation, includes variants with larger effect sizes, and features variable genetic architectures among individuals. Proposed work will solidify and extend these inferences in multiple respects, including by launching scaled-up mapping studies for a wider range of adaptive traits, and pursuing previous hints of epistasis involving adaptive variants. Proposed work will also open up a promising new system for studying The Genetic Basis of Early Stage Reproductive Isolation. African and European D. melanogaster show evidence of incompatibilities impacting viability and reproduction, but these have received no genetic study. This research will deploy a combination of incompatibility mapping and population genomics to identify specific incompatibility genes for further study, and it will advance understanding of the genetic architecture of the earliest stages of reproductive isolation. Finally, this research will clarify The Determinants of Genomic Diversity and Adaptive Potential. This work will feature experimental and computational studies on the relative roles of neutral and adaptive genetic diversity in future adaptation, and the most relevant ways to quantify each. It will also investigate the relative importance of different types of natural selection in shaping genomic diversity, including by probing the utility of genetic differentiation between populations to separate the signals of positive and negative selection. Collectively, this research is highly consequential for basic evolutionary genetics. It also holds strong medical relevance in terms of the relevance of local adaptation and epistasis for the genetic basis of human disease and infertility, and for understanding the evolutionary dynamics of insect disease vectors.

项目概要：基因组多样性与适应性和不相容性的结构 这项研究计划解决了遗传学与基因工程之间的界面上的基本但尚未解决的问题。 变异和进化过程。特别是，它侧重于三个相互关联的研究主题：（1） 适应性性状进化的遗传复杂性（2）早期生殖的遗传基础 隔离，和（3）基因组多样性和适应潜力的决定因素。它雄心勃勃，但 具有成本效益的果蝇实验与新的方法来分析大型基因组数据集。 D. melanogaster为这项工作提供了关键的优势。这个物种的全球扩张使得 研究适应性特征差异，部分生殖隔离，在不同的人群， 大约一万年。由于这个最近的时间尺度，适应性差异可以从遗传变异中检测出来。 果蝇的实验效率允许跨多代研究大型实验室种群。 其紧凑的基因组允许经济的测序。一旦发现相关基因，功能确认 基因组注释良好，遗传资源丰富，转基因工具丰富，有助于基因研究。 这项研究将加强对适应性性状进化的遗传复杂性的理解。初始 研究结果表明，适应的画像，往往开始于长期的遗传变异，包括 变异具有较大的效应量，并具有个体间可变的遗传结构。拟议工作 我将在多个方面巩固和扩展这些推论，包括启动扩大规模的测绘研究 更广泛的适应性特征，并追求以前的暗示上位性涉及适应性变异。 拟议的工作也将为研究早期阶段的遗传基础开辟一个有前途的新系统 生殖隔离。非洲和欧洲D.黑腹动物显示出不相容性的证据， 生存能力和繁殖能力，但这些都没有得到遗传研究。这项研究将部署一个组合 不亲和作图和群体基因组学的研究，以确定具体的不亲和基因， 它将促进对生殖隔离最早阶段的遗传结构的理解。 最后，本研究将阐明基因组多样性和适应潜力的决定因素。这 工作将以中性和适应性遗传的相对作用为特色的实验和计算研究 未来适应的多样性，以及量化每一种多样性的最相关方法。它还将调查相对 不同类型的自然选择在塑造基因组多样性方面的重要性，包括通过探索 种群间的遗传分化，分离正负选择信号。 总的来说，这项研究对基础进化遗传学具有重要意义。它还具有强大的 在局部适应性和上位性与人类遗传基础的相关性方面的医学相关性 疾病和不育，以及了解昆虫疾病媒介的进化动力学。