The gene regulatory basis of the genotype-phenotype map

项目摘要 这项研究计划旨在揭示形态特征在发育过程中是如何遗传编码的 并在进化过程中被改变。基因调控网络是产生一个细胞的物理特征的关键。 它们在生物体中起着重要作用，因为它们在发育过程中控制着每个基因的时空表达。现在 人们普遍认为，物种之间和种群内部（包括人类）的表型差异 群体中，通常由改变表达水平或时间的调节网络的变化引起。 尽管在这一领域取得了很大的进展，但我们对网络功能和进化的理解仍然缺乏。 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 和人口来产生特征这项研究将利用高度听话的果蝇 模型来回答这些问题。 该计划的第一个主题将解决一个基因调控网络控制快速发展的三个- 果蝇的三维解剖结构。我们将剖析构成这一结构的网络， 确定各个组件如何集成到网络中。与此同时，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， 将鉴定改变这些结构的三维形状的遗传变化。执行 这些研究将为基因调控网络的组装提供前所未有的视角， 修饰以产生组织结构的物理差异并产生精细的形态。 第二个主题包括对果蝇色素沉着特征的研究，这些特征在种群之间存在差异， 物种之间。大多数性状涉及多个基因座，这种多基因变异的大部分将来自于 在群体中持续存在而没有表型后果的常设变体。多重累积 遗传变化将被追踪，并与果蝇的一种蛹适应性色素沉着特征联系起来 黑腹菌研究中的色素沉着性状是由Hox转录因子控制的，这些转录因子高度表达于 苍蝇和人类共有的保守的身体模式基因。本项目将研究Hox基因 功能和进化的种群和物种之间，以确定如何基因调控网络， 这一特点出现并多样化。这项工作将提供一个深刻的分子理解如何表型是 生成，告知这些过程的性质，在不太听话的系统，包括人类。

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.