Evolutionary turnover of tissue-specific transcriptomes in Drosophila

果蝇组织特异性转录组的进化周转

• 批准号: 8986183
• 负责人: ARTYOM KOPP
• 金额: $ 27.15万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-12-15 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8986183
• 关键词: Activities of Daily Living; Affect; Age; Animals; Cells; ChIP-seq; Computing Methodologies; Data; Development; Drosophila genus; Event; Evolution; Fertility; Future; Gene Expression; Gene Targeting; Genes; Genetic; Genome; Genomics; Gland; Goals; Health; Human; Knock-out; Lead; Male Genital Organs; Mammals; Methods; Modeling; Molecular Evolution; Organ; Pattern; Phylogenetic Analysis; Post-Translational Protein Processing; Prevalence; Process; Proteins; RNA Interference; Recruitment Activity; Regulator Genes; Reproduction; Shapes; Specificity; Testing; Testis; Tissues; Transgenic Organisms; Ursidae Family; Variant; Work; aging gene; genome sequencing; in vivo; knock-down; male; neglect; novel; reproductive organ; transcription factor; transcriptome; transcriptome sequencing

DESCRIPTION (provided by applicant): All cells in the body share the same genome yet assume different identities and perform different functions. The functional capacity of an organ depends on the composition of its "transcriptome" - the subset of genes that are actively expressed in that organ. In the course of evolution, transcriptome turnover - qualitative remodeling of tissue-specific transcriptomes through gains and losses of gene expression - can lead to major changes in organ function. This is particularly true in the male reproductive system, which shows the highest rate of evolutionary divergence in all animals including humans and their closest relatives. The overall goal of this project is to achieve a systematic understanding of the genomic mechanisms responsible for transcriptome turnover in the male reproductive system using a group of closely related Drosophila species as a model. These genomic mechanisms span the range from the origin of entirely new genes to the recruitment of old genes for novel functions. Our first aim is to quantify the rate at which each of these mechanisms contributes to transcriptome turnover, in order to understand the relative importance of each mechanism in shaping organ function. In addition, we will determine whether transcriptome turnover occurs at a steady rate, or is accelerated during the origin of particular species. Our second aim is to characterize the changes in genetic regulatory networks that result from the recruitment of new genes into the reproductive organs. To accomplish this, we will develop a new transgenic method for in vivo protein modification, and use this method to identify the downstream targets of the regulatory genes that were recruited into the male reproductive system recently in evolution. Our third aim is to understand how the introduction of new genes into the transcriptome affects organ function and, especially, male fertility. This will be accomplished by systematically knocking out recently recruited genes of different age specifically in the reproductive organs. Finally, we will use computational methods to understand how tissue-specific recruitment events influence the subsequent evolution of genes and genomes. Together, these approaches will help elucidate the evolutionary processes that influence male fertility and, more generally, the genomic mechanisms that promote complexity and diversity in animal evolution.

描述(申请人提供)：身体中的所有细胞共享相同的基因组，但具有不同的身份和执行不同的功能。一个器官的功能能力取决于它的“转录组”的组成--该器官中活跃表达的基因的子集。在进化过程中，转录组转换--通过基因表达的得失对组织特异性转录体进行质的重塑--可以导致器官功能的重大变化。这在男性生殖系统中尤其如此，它在包括人类及其近亲在内的所有动物中显示出最高的进化分歧率。该项目的总体目标是以一组密切相关的果蝇物种为模型，系统地了解男性生殖系统中负责转录组转换的基因组机制。这些基因组机制跨越了从全新基因的起源到为新功能招募旧基因的范围。我们的第一个目标是量化每一种机制对转录组周转的贡献，以便了解每种机制在塑造器官功能方面的相对重要性。此外，我们将确定转录组的转换是以稳定的速度发生，还是在特定物种的起源过程中加速发生。我们的第二个目标是描述由于新基因被招募到生殖器官而导致的遗传调控网络的变化。为此，我们将开发一种新的转基因体内蛋白质修饰方法，并使用该方法来鉴定最近在进化过程中招募到男性生殖系统中的调控基因的下游靶点。我们的第三个目标是了解在转录组中引入新基因如何影响器官功能，特别是男性生育能力。这将通过系统地敲除最近招募的不同年龄的基因来实现，特别是在生殖器官中。最后，我们将使用计算方法来了解特定组织的招募事件如何影响基因和基因组的后续进化。总之，这些方法将有助于阐明影响男性生育能力的进化过程，以及更广泛地说，促进动物进化中复杂性和多样性的基因组机制。