Molecular Genetics of Evolutionary Innovations

进化创新的分子遗传学

• 批准号: 9277141
• 负责人: ARTYOM KOPP
• 金额: $ 32.62万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9277141
• 关键词: Anatomy; Animal Model; Animals; Behavior; Biological; Biological Models; Cell Differentiation process; Chronic Disease; Communicable Diseases; Complex; DNA Sequence; Drosophila genus; Elements; Evolution; Gene Expression; Gene Expression Regulation; Genes; Genetic; Genome; Genomics; Geology; Goals; Health; Human; Human Biology; Individual; Knowledge; Life; Modification; Molecular; Molecular Genetics; Molecular Profiling; Morphology; Mutation; Nutrient; Organ; Pathway interactions; Pattern; Phenotype; Planet Earth; Population; Predisposition; Recruitment Activity; Regulatory Element; Regulatory Pathway; Research; Risk Factors; Series; Structure; Testing; Tissues; Translating; Variant; Work; cell type; innovation; novel; public health relevance; single molecule; social organization; trait

Project summary “Evolutionary innovation” refers to the origin of entirely new traits, as opposed to the modification of existing traits. Although such novelties are relatively rare, all the complexity and diversity of life has ultimately been shaped by evolutionary innovations that occurred in a nested pattern, with every innovation dependent on many earlier novelties. Despite their critical importance for everything from geological nutrient cycles that support all life on Earth to human sentience that distinguishes us from our closest relatives, the molecular mechanisms of evolutionary innovations are understood far less than the evolution of existing traits. This is true at all levels of biological organization, from single molecules to the most complex features of animal form and function. We understand the evolution of existing organs and cell types better than the origin of new ones; quantitative variation in gene expression has been explored in much greater detail than the origin of novel regulatory pathways; much more is known about the evolution of existing genes than about the origin of new genes, and so on. It is this gap in our knowledge that motivates our work. To achieve a comprehensive understanding of evolutionary innovations, it is necessary to connect novelties at all levels of biological organization: from new functional elements in the genome, to new genetic pathways, to new morphological structures. Research in our lab will advance in three directions, using the Drosophila model system. First, we will identify the molecular mechanisms responsible for the origin of new morphological structures that evolved recently within Drosophila. We will identify the DNA sequences that gave rise to phenotypic innovations, and reconstruct the cell differentiation pathways than translate these changes into novel morphologies. Second, we will examine the genomic mechanisms that qualitatively remodel the gene expression profiles of different organs and cell types, and quantify the relative contributions of each type of genomic change to the turnover of genes expressed in each tissue. We will test whether the regulatory circuits that control gene expression evolve predominantly by incorporating individual genes, or by recruitment of larger genetic modules. Third, we will identify the molecular changes responsible for the origin of new regulatory elements that control gene expression from non-functional ancestral sequences. By focusing on novel regulatory elements that evolved within natural populations of a single species, we will reconstruct the series of mutations that create new functional elements in the genome, and elucidate the impact of these mutations on gene regulation. Together, these approaches will promote a deep mechanistic understanding of evolutionary innovations.

项目摘要 “进化创新”指的是全新性状的起源，而不是对 现有的特征。尽管这种新奇的事物相对罕见，但生命的复杂性和多样性 最终被以嵌套模式发生的进化创新所塑造，每一次创新 依赖于许多早期的新奇事物。尽管它们对从地质学到生物学的一切都至关重要 营养循环，支持地球上的所有生命，以人类的感知，使我们从我们最接近的 相对而言，进化创新的分子机制远不如进化 现有的特征。这在生物组织的各个层次都是如此，从单个分子到最多的 动物形态和功能的复杂特征。我们了解现有器官和细胞的进化 类型比新的起源更好;基因表达的定量变化已经在 比新的调控途径的起源更详细;更多的是了解的演变， 而不是新基因的起源，等等。正是我们知识上的这一差距， 我们的工作 要实现对进化创新的全面理解， 生物组织各个层次的新事物：从基因组中的新功能元件，到新的遗传物质， 新的形态结构。我们实验室的研究将在三个方向上推进， 果蝇模型系统。首先，我们将确定负责新的起源的分子机制。 最近在果蝇中进化的形态结构。我们将鉴定出 引起了表型创新，并重建细胞分化途径，而不是翻译这些 变成了新的形态第二，我们将研究基因组机制， 重塑不同器官和细胞类型的基因表达谱， 每种类型的基因组变化对每个组织中表达的基因的周转的贡献。我们将 测试控制基因表达的调节回路是否主要通过整合 单个基因，或通过招募更大的遗传模块。第三，我们将识别分子变化 负责控制基因表达的新调控元件的起源， 祖先序列通过关注在自然种群中进化的新的调节元件， 我们将重建一系列突变，这些突变在细胞中产生新的功能元件。 基因组，并阐明这些突变对基因调控的影响。总之，这些方法将 促进对进化创新的深刻机械理解。