Genomic Basis of Vertebrate Diversity

脊椎动物多样性的基因组基础

• 批准号: 7880774
• 负责人: DAVID M KINGSLEY
• 金额: $ 260.09万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-19 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7880774
• 关键词: Animals; Behavior; Behavioral; Biological Models; Chromosome Mapping; DNA Sequence Rearrangement; Data; Disease susceptibility; Environment; Fishes; Gasterosteidae; Gene Mutation; Genes; Genetic; Genomics; Goals; Human; Measures; Modeling; Molecular; Morphology; Mus; Mutation; Organism; Pathway interactions; Physiological; Physiology; Play; Population; Population Genetics; Role; Testing; Variant; Vertebrates; Y Chromosome; base; comparative; comparative genomics; genome-wide; human population genetics; innovation; sex; trait

DESCRIPTION: The long-term goal of this project is to understand the genomic mechanisms that generate phenotypic diversity in vertebrates. Rapid progress in genomics has provided nearly complete sequences for several organisms. Comparative analysis suggests many fundamental pathways and gene networks are conserved between organisms. And yet, the morphology, physiology, and behavior of different species are obviously and profoundly different. What are the mechanisms that generate these key differences? Are unique traits controlled by few or many genetic changes? What kinds of changes? Are there particular genes and mechanisms that are used repeatedly when organisms adapt to new environments? Can better understanding of these mechanisms help explain dramatic differences in disease susceptibility that also exist between groups? The Stanford CEGS will use an innovative combination of approaches in fish, mice, and humans to identify the molecular basis of major phenotypic change in natural populations of vertebrates. Specific aims include: 1) cross stickleback fish and develop a genome wide map of the chromosomes, genes, and mutations that control a broad range of new morphological, physiological, and behavioral traits in natural environments; 2) test which population genetic measures provide the most reliable "signatures of selection" surrounding genes that are known to have served as the basis of parallel adaptive change in many different natural populations around the world; 3) assemble the stickleback proto Y chromosome and test whether either sex or autosomal rearrangements play an important role in generating phenotypic diversity, or are enriched in genomic regions that control phenotypic change; 4) test whether particular genes and mechanisms are used repeatedly to control phenotypic change in many different vertebrates. Preliminary data suggests that mechanisms identified as the basis of adaptive change in natural fish populations may be broadly predictive of adaptive mechanisms across a surprisingly large range of animals, including humans. Genetic regions hypothesized to be under selection in humans will be compared to genetic regions under selection in fish. Regions predicted to play an important role in natural human variation and disease susceptibility will be modeled in mice, generating new model systems for confirming functional variants predicted from human population genetics and comparative genomics.

描述：该项目的长期目标是了解在脊椎动物中产生表型多样性的基因组机制。基因组学的快速进步为几种生物提供了几乎完整的序列。比较分析表明，许多基本途径和基因网络在生物之间是保守的。然而，不同物种的形态，生理和行为显然是截然不同的。产生这些关键差异的机制是什么？独特的特征是否受到很少或许多遗传变化的控制？什么样的变化？当生物适应新环境时，是否有特定的基因和机制反复使用？对这些机制的更好理解能否有助于解释群体之间也存在的疾病敏感性的巨大差异？斯坦福大学将使用鱼类，小鼠和人类方法的创新组合来确定脊椎动物自然种群重大表型变化的分子基础。具体目的包括：1）交叉粘性鱼并开发了染色体，基因和突变的基因组宽图，这些图控制自然环境中各种新的形态，生理和行为特征； 2）测试哪些种群遗传措施为周围基因提供了最可靠的“选择”，这些基因被称为世界上许多不同自然种群的平行自适应变化的基础； 3）组装粘性原型染色体并测试性别或常染色体重排是否在产生表型多样性中起重要作用，还是在控制表型变化的基因组区域中富集； 4）测试是否反复使用特定的基因和机制来控制许多不同脊椎动物的表型变化。初步数据表明，被确定为天然鱼类种群自适应变化的基础的机制可能可以广泛预测包括人类在内的大量动物（包括人类）的自适应机制。假设在人类中被选择的遗传区域将与鱼类中正在选择的遗传区域进行比较。预计将在自然人类变异中发挥重要作用，并且将在小鼠中建模疾病敏感性，从而生成新的模型系统，以确认从人群遗传学和比较基因组学预测的功能变异。