Collaborative: The Role of Gene Duplication in the Evolution of Chordate Developmental Regulation

协作：基因复制在脊索动物发育调控进化中的作用

• 批准号: 0321461
• 负责人: Chris Amemiya
• 金额: $ 31.5万
• 依托单位: Benaroya Research Institute at Virginia Mason
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0321461&HistoricalAwards=false
• 关键词: Collaborative; Role; Gene; Duplication; Evolution

0321461AmemiyaThe interconnection between development and evolution (Devo-Evo) was recognized in the mid-1800's by Darwin and Haeckel, though it has not been until very recently that the mechanistic basis for this crucial link has been readily addressable to experimental biology. In this collaborative project a question concerning the developmental evolution of the vertebrate bauplan is addressed: what are the developmental and evolutionary consequences of gen(om)e duplication during vertebrate phylogeny? It has been known for a long time that the evolution of the vertebrates was associated with a major expansion of genome size, either by gene or genome duplications. The present project focuses on the Hox gene clusters, a complex of genes that encode transcription factors known to be involved in a wide range of biological activities, including the development of the body axis, fins and limbs and many other organs. Vertebrates have the peculiar tendency to duplicate and retain Hox clusters, while no such tendency is apparent in invertebrates. It is not known why vertebrates have this tendency and whether these duplication events had an influence on the evolution of the vertebrate body plan. The goals of this project are to understand the extent and history of Hox cluster duplications among the vertebrates (specifically focusing on the teleosts), and to determine whether such duplications have facilitated evolutionary change both functionally and morphologically. We will use the ray finned fish radiation, in which the most recent Hox cluster duplication has been documented, as our experimental focus. The experimental approach involves: (1) tracing the patterns of molecular evolution of the Hox clusters and their genes, with the aim to determine whether the teleost Hox cluster duplication was coincident with the teleost radiation; (2) using Bacterial Artificial Chromosome technology and computational genomics methods in order to detect changes in the organization of clusters as well as identify changes in the pattern of non-coding sequence conservation; (3) employing BAC-reporter transgenesis as a comparative tool to draw inferences with respect to the effects of gene duplication on expression patterns; and (4) employing statistical tests to both coding and non-coding regions of Hox clusters to draw inferences with regard to the evolutionary forces (selection/drift) acting on duplicated genes and clusters. This investigation represents a part of an ongoing collaboration between three investigators of diverse backgrounds: Frank Ruddle (Yale University) has expertise in mammalian developmental biology, mouse transgenesis and homeobox genes; Gunter Wagner (Yale University) has an extensive background in quantitative-mathematical approaches to evolution and developmental evolution; and Chris Amemiya (formerly Boston University and now at Virginia Mason Research Center) has expertise in vertebrate zoology, genetics, and genomics. Each investigator is focussing on different aspects of the project but with the same overall goals in mind. This consortial approach has proven effective in the past and considerable progress has been made since the previous funding cycle. The broad impact of this proposal is measured in two ways: (1) by employing a highly interdisciplinary and novel approach for evaluating a complex problem in biology; and (2) by providing a wealth of research and educational resources. These training opportunities, including new summer traineeships for teachers and undergraduates of underrepresented minorities.

19世纪中期，达尔文和海克尔认识到了发育和进化之间的相互联系(发展-进化)，尽管直到最近，这一关键联系的机制基础才容易地用实验生物学来解决。在这个合作项目中，一个关于脊椎动物Bauplan的发育进化的问题被解决了：在脊椎动物系统发育过程中，基因(Om)重复的发展和进化后果是什么？众所周知，脊椎动物的进化与基因组大小的重大扩张有关，无论是通过基因复制还是基因组复制。本项目的重点是HOX基因簇，这是一种编码转录因子的基因复合体，已知参与广泛的生物学活动，包括体轴、鳍和四肢以及许多其他器官的发育。脊椎动物有复制和保留HOX簇的特殊倾向，而无脊椎动物则没有明显的这种倾向。目前尚不清楚脊椎动物为什么会有这种倾向，以及这些重复事件是否对脊椎动物身体计划的进化产生了影响。该项目的目标是了解脊椎动物(特别是硬骨鱼)之间HOX簇重复的范围和历史，并确定这种重复是否促进了功能和形态上的进化变化。我们将使用射线鳍鱼辐射作为我们的实验重点，在该辐射中，最近的Hox星团复制已经被记录在案。实验方法包括：(1)追踪HOX簇及其基因的分子进化模式，以确定硬骨HOX簇复制是否与硬骨辐射一致；(2)使用细菌人工染色体技术和计算基因组学方法，以检测簇组织的变化以及识别非编码序列保守模式的变化；(3)使用BAC-Report转基因作为比较工具，以推断基因复制对表达模式的影响；以及(4)对HOX簇的编码区和非编码区进行统计检验，以推断作用于重复基因和簇的进化力(选择/漂移)。这项研究是三位具有不同背景的研究人员之间持续合作的一部分：Frank Ruddle(耶鲁大学)拥有哺乳动物发育生物学、小鼠转基因和同源盒基因方面的专业知识；Gunter Wagner(耶鲁大学)在进化和发育进化的定量数学方法方面拥有丰富的背景；Chris Ameiya(前波士顿大学，现供职于弗吉尼亚·梅森研究中心)拥有脊椎动物动物学、遗传学和基因组学方面的专业知识。每个调查员都专注于项目的不同方面，但心中有相同的总体目标。这一联合办法在过去被证明是有效的，自上一个供资周期以来取得了相当大的进展。这项建议的广泛影响通过两种方式来衡量：(1)采用高度跨学科和新颖的方法来评估生物学中的复杂问题；(2)通过提供丰富的研究和教育资源。这些培训机会，包括为代表不足的少数群体的教师和本科生提供新的暑期实习生职位。