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RUI: There is more to the Hox code than you thought - the role of the "Hox fin/limb building toolkit" genes in the evolution of vertebrate diversity

RUI：Hox 代码比你想象的更多——“Hox 鳍/肢构建工具包”基因在脊椎动物多样性进化中的作用

基本信息

批准号：
1656487
负责人：
Karen Crow
金额：
$ 50.96万
依托单位：
San Francisco State University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-02-01 至 2024-01-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1656487&HistoricalAwards=false
关键词：
RUI There more Hox code

项目摘要

One of the primary goals of Evolutionary Developmental Biology is to understand the genetic basis of morphological evolution. While there is intense interest in cataloging and conserving diversity in nature, we are only beginning to understand the mechanisms responsible for generating biodiversity. Fins and limbs are homologous structures that are patterned by a shared genetic repertoire of HoxA/D expression, which has been referred to as the 'Hox fin/limb building toolkit'. A unique expression pattern is associated with the most famous example of a novel limb modification that specifies digit identity and the origin of the thumb in the human hand. The pattern also occurs in fishes and sharks, indicating that it arose in the common ancestor of jawed vertebrates. Recent evidence indicates that the Hox code is more complex than previously recognized, yet few derived morphologies have been evaluated. This project examines the role of Hox genes in the evolution and development of novel fin/limb modifications in three divergent lineages that exhibit unique body plan features, and for which the ecological or physiological significance is understood. This research engages undergraduates in using genomic tools to answer newly tractable questions, and is based at a public state university that serves a large undergraduate population with a high proportion of underrepresented minorities. The focal taxa (sharks, manta rays, paddlefish and surfperches) are highly charismatic and command intense interest in the public eye. The PI has a track record of involving undergraduates in research, professional presentations, and publication, and will develop educational materials to engage the general public in understanding the genetic underpinnings of the evolution of diversity, including fin and limb modifications that share deep homology with our own hands and feet, while serving the NSF's mission of connecting research, education and public outreach. Vertebrates exhibit a remarkable array of fin and limb modifications that are clear homologs of human appendages, yet the genetic underpinnings of most have not been characterized. Their variety forms the basis for the observed morphological diversity in vertebrates, and their novelty provides a unique opportunity for elucidating general principles of morphological evolution. The overarching goal of this research is to evaluate the modularity and plasticity of the Hox fin/limb-building program in the evolution of morphological diversity in vertebrates by addressing the following questions: - Do claspers or cephalic lobes represent independent sets of paired appendages in modern cartilaginous fishes that are patterned by the Hox fin/limb pathway genes? - Are novel deployments of the Hox fin/limb pathway genes associated with morphological diversity in medial fin structures such as the genital protuberance in surfperch anal fin, or the elongated caudal fin in paddlefish?This research will employ a functional genomic screen composed of multiple approaches including RNASeq, in situ hybridization, functional assays, and evaluation of conserved/novel regulatory sequences for the Hox fin/limb toolkit genes that are known to pattern fins/limbs in model taxa.

进化发育生物学的主要目标之一是了解形态进化的遗传基础。虽然人们对编目和保护自然界的多样性有着浓厚的兴趣，但我们才刚刚开始了解生物多样性产生的机制。鳍和肢是同源结构，其由HoxA/D表达的共享遗传库形成，其被称为“Hox鳍/肢构建工具包”。一个独特的表达模式与一个新的肢体修饰的最著名的例子，指定手指身份和拇指在人类手中的起源。这种模式也出现在鱼类和鲨鱼中，表明它起源于有颌脊椎动物的共同祖先。最近的证据表明，Hox代码比以前认识到的更复杂，但很少有衍生的形态进行了评估。该项目研究了Hox基因在三个不同谱系中的新鳍/肢修饰的进化和发展中的作用，这些谱系表现出独特的身体计划特征，并了解其生态或生理意义。这项研究让大学生使用基因组工具来回答新的易处理的问题，并以一所公立州立大学为基础，该大学为大量本科生人口提供服务，其中少数民族的比例很高。重点类群（鲨鱼、曼塔、白鲟和冲浪鲈鱼）极具魅力，引起公众的强烈兴趣。PI有一个让本科生参与研究，专业演讲和出版的记录，并将开发教育材料，让公众了解多样性进化的遗传基础，包括与我们自己的手和脚共享深度同源性的鳍和肢体修改，同时服务于NSF的连接研究，教育和公共宣传的使命。脊椎动物展示了一系列令人瞩目的鳍和肢的变化，这些变化显然是人类附属物的同源物，但大多数的遗传基础还没有被描述。它们的多样性构成了脊椎动物形态多样性的基础，它们的新奇为阐明形态进化的一般原则提供了独特的机会。本研究的总体目标是评估的模块化和可塑性的Hox鳍/肢体建设计划在脊椎动物的形态多样性的演变，解决以下问题：-扣或头叶代表独立的成对附属物在现代软骨鱼类的图案由Hox鳍/肢体通路基因？- 是新部署的Hox鳍/肢体通路基因与形态多样性的中间鳍结构，如生殖器突起冲浪鱼的臀鳍，或细长的尾鳍白鲟？这项研究将采用功能基因组筛选，包括RNASeq，原位杂交，功能测定和评估Hox fin/limb工具包基因的保守/新调控序列，这些基因已知在模型分类群中形成鳍/肢的模式。