Evolutionary turnover of tissue-specific transcriptomes in Drosophila

描述（由申请人提供）：体内所有细胞共享相同的基因组，但具有不同的身份并执行不同的功能。一个器官的功能能力取决于其“转录组”的组成--在该器官中活跃表达的基因子集。在进化过程中，转录组更新-通过基因表达的获得和损失对组织特异性转录组进行质的重塑-可以导致器官功能的重大变化。这在雄性生殖系统中尤其如此，在包括人类及其近亲在内的所有动物中，雄性生殖系统的进化分化率最高。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周转的基因组机制。这些基因组机制涵盖了从全新基因的起源到招募旧基因以实现新功能的范围。我们的第一个目标是量化这些机制中的每一种对转录组周转的贡献率，以了解每种机制在塑造器官功能中的相对重要性。此外，我们将确定转录组周转是否以稳定的速度发生，或者在特定物种的起源过程中加速。我们的第二个目标是描述基因调控网络的变化，这些变化是由新基因进入生殖器官引起的。为了实现这一点，我们将开发一种新的转基因方法，在体内蛋白质修饰，并使用这种方法来确定最近在进化中招募到男性生殖系统的调控基因的下游目标。我们的第三个目标是了解将新基因引入转录组如何影响器官功能，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组织特异性募集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雄性生育力的进化过程，以及更普遍的促进动物进化复杂性和多样性的基因组机制。

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.