Exploring the genetic causes and phenotypic consequences of transcriptome turnover

探索转录组更新的遗传原因和表型后果

• 批准号: 9530383
• 负责人: Ammon Thompson
• 金额: $ 6.12万
• 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: 2017-07-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9530383
• 关键词: Brain; CRISPR/Cas technology; Cells; Cellular Structures; Characteristics; Complement; Complex; Consequentialism; Coupled; Data; Data Set; Development; Dimensions; Disease; Drosophila genus; Drosophila melanogaster; Ectopic Expression; Essential Genes; Evolution; Experimental Genetics; Expression Profiling; Eye; Fertilization; Frequencies; Gene Deletion; Gene Duplication; Gene Expression; Gene Expression Regulation; Genes; Genetic; Genetic Materials; Genetic Research; Genome; Genomics; Gland; Health; Home environment; Human; Knock-out; Knowledge; Link; Male Genital Organs; Measures; Modeling; Mutation; Organ; Organism; Outcome; Outcomes Research; Phenotype; Phylogeny; Physiological; Play; Primates; Process; Proteins; RNA Interference; Research; Research Personnel; Role; Running; Shapes; Source; Statistical Data Interpretation; Techniques; Testing; Testis; Time; Tissues; Training; Transgenic Organisms; Untranslated RNA; body system; cell type; comparative; duplicate genes; experience; experimental study; insight; knock-down; male; male fertility; markov model; novel; rate of change; reproductive organ; success; tool; transcription factor; transcriptome; transcriptomics

Project Summary Transcriptome turnover is the process by which an organ system or cell type gains and loses the expression of genes over evolutionary time. Comparative data indicate that gains and losses of genes within a tissue-specific transcriptome are widespread phenomena that can have a large impact on tissue function and physiological characteristics of organisms. Genes enter and leave the tissue transcriptome through two classes of genomic changes: structural and regulatory. Structural changes are changes in genome content that occur through processes such as gene duplication and deletion. Regulatory changes are changes in the tissue- specific expression of conserved genes, which occur through the gain or loss of non-coding sequences that control the expression of genes. These regulatory alterations happen through either cis (mutations in non- coding sequences that regulate a gene directly) or trans changes (mutations that alter an upstream regulating protein such as a transcription factor). The mechanism by which genes turnover in the tissue transcriptome may predict their likelihood of cooption into new regulatory circuits in the new tissue and of playing an adaptive role in the new transcriptome. This research seeks to investigate the relative rates of structural and regulatory turnover and the relative essentiality of genes gained through these mutational processes. Comparative transcriptome profiles, evolutionary models and statistical analysis will be used to estimate the relative frequency of structural versus regulatory turnover in rapidly evolving reproductive organs in 11 species in the D. melanogater species group: the structurally complex testes and structurally simple accessory glands. To compare their essentiality expression of genes that gained expression through regulatory versus structural mechanisms will be knocked down in D. melanogaster accessory glands to directly compare their essentiality to organ function. The impact of transcription factor cooption on the transcriptome and phenotype of the accessory glands will be investigated through transgenic techniques. The outcome of this research will be an understanding of the frequency and phenotypic impact of genomic mutation types that contribute to transcriptome turnover. This will provide a more detailed understanding of which mutational processes may be the most important sources of new adaptive genetic materials for evolving organs. Characterizing the rate and phenotypic impact of the forces moving genes in and out of organ transcriptomes—whether structural or regulatory; cis or trans—will also allow researchers to use comparative transcriptomics data to home in on the functionally important aspects of the transcriptome when studying human health and disease.

项目摘要 转录组周转率是器官系统或细胞类型会获得并失去的过程 基因在进化时期的表达。比较数据表明，基因的收益和损失 组织特异性转录组是宽度现象，可能对组织功能和 生物的生理特征。基因通过两个类别输入并离开组织转录组 基因组变化：结构和调节性。结构性变化是发生的基因组含量的变化 通过基因复制和缺失等过程。调节性变化是组织的变化 组成基因的特定表达，这是通过非编码序列的增益或丢失而发生的 控制基因的表达。这些调节性改变是通过顺式发生的（非 - 直接调节基因的编码序列）或翻译（改变上游调节的突变 蛋白质，例如转录因子）。基因转录组中基因周转的机制 可能可以预测他们在新组织中加入新调节电路的可能性并进行自适应 在新转录组中的角色。 这项研究旨在研究结构和法规周转的相对率，以及 通过这些突变过程获得的基因的相对重要性。比较转录组轮廓， 进化模型和统计分析将用于估计结构的相对频率与 黑色素菌种群中11种生殖器官快速发展的监管转移： 结构复杂的测试和结构简单的附件腺。比较他们的本质 通过调节与结构机制获得表达的基因的表达将被敲击 在D. melanogaster附属腺体中直接将其与器官功能进行比较。影响 在附件腺的转录组和表型上的转录因子合作将是 通过转基因技术进行了研究。 这项研究的结果将是对 有助于转录组周转率的基因组突变类型。这将提供更详细的 了解哪些突变过程可能是新的适应性通用的最重要来源 不断发展的器官的材料。表征力在和中移动基因的力的速率和表型影响 在器官转录组中，无论是结构性还是调节性；顺式或跨性别 - 将允许研究人员使用 比较转录组学数据在转录组的功能上重要方面到HOME时 研究人类健康和疾病。