The gene regulatory basis of the genotype-phenotype map

项目总结 这项研究计划试图揭示形态特征是如何在发育过程中被遗传编码的 并在进化过程中进行了修改。基因调控网络是产生人体生理特征的关键 生物体，因为它们控制着每个基因在发育过程中的空间和时间表达。现在是时候了 人们普遍认为，物种之间和种群内的表型差异，包括人类 人口，通常是由改变表达水平或时机的调控网络的变化引起的。 尽管在这一领域取得了很大进展，但我们对网络功能和演化的理解还存在以下几个方面 主要领域：(1)网络的变化如何产生新的特征？(2)网络如何影响 细胞在发育组织中的行为？(3)影响基因调控的突变如何渗透到网络中 和人口导致的特征吗？这项研究将利用高度驯化的黑腹果蝇 模型来回答这些问题。 本节目的第一个主题将涉及控制快速进化的三个基因调控网络-- 果蝇的立体解剖结构。将对此结构进行模式划分的网络 确定各个组件如何集成到网络中。同时，拟议的研究将 追踪这些网络和驱动形态发生的细胞过程之间的联系。最后， 改变这些结构三维形状的基因变化将被识别出来。表演 这些研究将提供一个前所未有的视角，了解基因调控网络是如何组装的，以及 经过修改以在组织结构中产生物理差异并产生精细的形态。 第二个主题包括对果蝇色素特性的研究，这些特性在不同的种群和 在物种之间。大多数性状涉及多个基因座，而这种多基因变异的很大一部分将来自 在种群中持续存在而不会产生表型后果的常备变异。倍数的积累 将追踪果蝇的基因变化，并将其与推测的适应性色素沉积特性联系起来 黑猩猩。研究中的色素沉着性状由Hox转录因子控制，这些转录因子是高度 苍蝇和人类共有的保守的身体模式基因。这个项目将检测HOX基因 在种群内和物种之间的功能和进化，以确定基因调控网络如何 这一特点出现了，而且多样化了。这项工作将提供一个深入的分子理解如何表型 生成，在不太容易处理的系统(包括人类)中通知这些过程的性质。

PROJECT SUMMARY This research program seeks to reveal how morphological traits are genetically encoded during development and modified during evolution. Gene regulatory networks are key to generating the physical features of an organism, as they govern the spatial and temporal expression of each gene during its development. It is now well accepted that phenotypic differences between species and within populations, including the human population, are often caused by changes to regulatory networks which alter expression levels or timing. Despite much progress in this field, our understanding of network function and evolution is lacking in several major areas: (1) how do new traits emerge from changes to networks? (2) how do networks influence the behavior of cells in developing tissues? (3) how do mutations that affect gene regulation permeate networks and populations to cause traits? This research will leverage the highly tractable Drosophila melanogaster model to answer these questions. The first theme of this program will address a gene regulatory network controlling a rapidly evolving three- dimensional anatomical structure in Drosophila. The network which patterns this structure will be dissected to determine how individual components became integrated into the network. In parallel, the proposed studies will trace the connections between these networks and the cellular processes that drive morphogenesis. Finally, genetic changes which alter the three-dimensional shape of these structures will be identified. Performing these studies will provide an unprecedented view of how gene regulatory networks are assembled and modified to generate physical differences in tissue structure and produce elaborate morphologies. The second theme comprises studies on Drosophila pigmentation traits that differ among populations and between species. Most traits involve multiple loci, and much of this polygenic variation will be derived from standing variants that persist in populations without phenotypic consequences. The accumulation of multiple genetic changes will be traced and connected to a putatively adaptive pigmentation trait in Drosophila melanogaster. The pigmentation trait under study is controlled by Hox transcription factors, which are highly conserved body-patterning genes shared between flies and humans. This project will examine Hox gene function and evolution in populations and between species to determine how the gene regulatory network for this trait arose and diversified. This work will provide a deep molecular understanding of how phenotypes are generated, informing the nature of these processes in less tractable systems, including humans.