The Basal State of Hox Gene Control and Function in Ray-finned Fish Phylogeny

射线鳍鱼系统发育中Hox基因控制和功能的基础状态

• 批准号: 0447478
• 负责人: Chi-hua Chiu
• 金额: $ 41.98万
• 依托单位: Rutgers University New Brunswick
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0447478&HistoricalAwards=false
• 关键词: Basal; State; Hox; Gene; Control

Hox genes encode transcriptional regulator proteins that play an important role in body axis formation and are likely to have a major influence on the development and evolution of body plans. Human and mouse possess thirty-nine Hox genes distributed on four Hox clusters, A, B, C, D. Recent studies have found a dynamic mode of Hox cluster evolution occurred in the ray-finned fishes. Derived ray-finned fishes (teleosts) such as zebrafish and pufferfish have 7-8 Hox clusters that have undergone considerable sequence evolution. Hence, comparisons of Hox gene control and function between taxa such as zebrafish and human are complicated. The PI will investigate Hox gene control and function in the bichir (Polypterus senegalus), the most basal living ray-finned fish that possesses several primitive fish morphological characters including primitive pectoral fins. The PI has already shown that the bichir has a single HoxA cluster; hence, the bichir does not have the duplication that produced extra HoxA clusters in derived teleosts. This research has three Objectives: (1) to determine the Hox complement of clusters and genes in the bichir, (2) to utilize bichir HoxA cluster sequences to identify HoxA11 cis-regulatory elements that are responsible for the expression pattern in an ancestral fish fin, and (3) to survey for the presence of so-identified ancestral HoxA11 cis-regulatory elements in additional teleost lineages. The experimental approach involves (1) cloning, sequencing, and informatics of bichir Hox clusters, (2) using transgenic reporter technologies to functionally test candidate ancestral HoxA11 cis-regulatory sequences, and (3) isolating HoxA clusters of additional teleost lineages with targeted sequencing of so-identified ancestral HoxA11 cis-regulatory sequences. Results of this research will contribute to a mechanistic foundation for the evolution of terrestrial limbs from aquatic fins. Knowledge on Hox gene control and function in the earliest ray-finned fishes will enhance understanding of the evolutionary forces acting on duplicated Hox clusters of derived ray-finned fishes. This research has/will generated a large body of genomic sequence data of Hox clusters in the bichir and other ray-finned fishes that are/will be deposited in GenBank and shared openly in the scientific community via research publications and websites. In terms of broader impact, this project will provide good training opportunities for undergraduate, graduate, and postdoctoral students in the postgenomic era.

Hox 基因编码转录调节蛋白，在身体轴的形成中发挥重要作用，并可能对身体计划的发育和进化产生重大影响。人和小鼠拥有39个Hox基因，分布在A、B、C、D 4个Hox簇上。最近的研究发现射线鳍鱼中存在Hox簇进化的动态模式。斑马鱼和河豚等衍生的射线鳍鱼类（硬骨鱼）具有 7-8 个 Hox 簇，这些簇经历了相当大的序列进化。因此，斑马鱼和人类等类群之间 Hox 基因控制和功能的比较很复杂。 PI 将研究 bichir（塞内加尔多鳍鱼）中的 Hox 基因控制和功能，bichir 是现存最基础的射线鳍鱼类，具有多种原始鱼类形态特征，包括原始胸鳍。 PI 已经表明 bichir 有一个 HoxA 簇；因此，bichir 不具有在派生的硬骨鱼中产生额外 HoxA 簇的重复。这项研究有三个目标：（1）确定bichir中簇和基因的Hox互补，（2）利用bichir HoxA簇序列来鉴定负责祖先鱼鳍表达模式的HoxA11顺式调节元件，以及（3）调查其他硬骨鱼谱系中是否存在如此鉴定的祖先HoxA11顺式调节元件。实验方法包括（1）bichir Hox簇的克隆、测序和信息学，（2）使用转基因报告技术对候选祖先HoxA11顺式调控序列进行功能测试，以及（3）通过对如此鉴定的祖先HoxA11顺式调控序列进行靶向测序来分离其他硬骨鱼谱系的HoxA簇。这项研究的结果将为水生鳍进化为陆生肢体奠定机制基础。关于最早的射线鳍鱼类的 Hox 基因控制和功能的知识将增强对作用于衍生射线鳍鱼类的重复 Hox 簇的进化力量的理解。这项研究已经/将产生大量比齐尔鱼和其他射线鳍鱼类的 Hox 簇基因组序列数据，这些数据将/将存放在 GenBank 中，并通过研究出版物和网站在科学界公开共享。从更广泛的影响来看，该项目将为后基因组时代的本科生、研究生和博士后提供良好的培养机会。