CAREER: Phenotypic and developmental effects of enhancer variation on cichlid craniofacial evolution

职业：增强子变异对慈鲷颅面进化的表型和发育影响

• 批准号: 1942178
• 负责人: Kara Powder
• 金额: $ 116.72万
• 依托单位: Clemson University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-15 至 2025-02-28
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1942178&HistoricalAwards=false
• 关键词: CAREER; Phenotypic; developmental; effects; enhancer

Genes are precisely turned on and off by their regulatory elements. This project examines how altered gene regulation can generate changes in animal development, specifically in the facial skeleton. This work will identify regulatory elements through genome analysis, quantify how altered gene regulation during embryonic development changes facial shape, and assess the effects of DNA mutations on regulatory function using microscopy. Given that (1) 85% of disease-causing mutations affect gene regulation and (2) changes to gene regulation are predicted to be a major source of evolutionary diversity, this work will provide insights into how DNA changes can produce both natural variation in animal development and disease in humans. Educational activities will improve factors key in retention of undergraduate and K-12 students in STEM disciplines. This will be accomplished through (1) mentorship of undergraduates and (2) creation of inquiry-based activities for the middle school classroom that will be implemented in local schools and distributed to educators nationally. Understanding the functional impact of genetic variation in cis-regulation is a major gap in our understanding of the generation of phenotypic diversity. The research objective of this project is to analyze the phenotypic function of non-coding, gene regulatory enhancers within the context of craniofacial evolution in cichlid fishes, a textbook example of an adaptive radiation. The specific aims are to (1) utilize four complementary genomic strategies to comprehensively identify candidate enhancers with genetic variation, (2) quantify phenotypic and transcriptional effects of modulating enhancer activity using CRISPR-Cas9, and (3) empirically assess the effect of genetic variation on enhancer activity. With a focus on the functional effect of enhancers in vivo in terms of activity, transcriptional regulation, and effect on phenotype, this work will address a major gap in knowledge of the genotype-phenotype relationship. These data will provide empirical information for those designing models of the grammar of gene regulation, a framework to significantly accelerate the discovery and systematic documentation of causal genetic variations in non-coding DNA, and experimental evidence for a central theory of Evolutionary Developmental Biology (Evo-Devo).This project is jointly funded by the Developmental Systems Cluster of IOS, and by the Established Program to Stimulate Competitive Research (EPSCoR)This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

基因正是由它们的调控元件来开启和关闭的。这个项目研究改变的基因调控如何在动物发育中产生变化，特别是在面部骨骼中。这项工作将通过基因组分析确定调控元件，量化胚胎发育过程中改变的基因调控如何改变面部形状，并使用显微镜评估DNA突变对调控功能的影响。鉴于(1)85%的致病突变影响基因调控，(2)基因调控的变化被预测为进化多样性的主要来源，这项工作将为DNA变化如何在动物发育和人类疾病中产生自然变异提供洞察力。教育活动将改善留住STEM学科本科生和K-12学生的关键因素。这将通过(1)指导本科生和(2)为中学课堂创建探究性活动来实现，这些活动将在当地学校实施，并分发给全国教育工作者。理解顺式调控中遗传变异的功能影响是我们理解表型多样性产生的一个主要差距。这个项目的研究目标是分析非编码的基因调控增强子在慈鱼头面部进化的背景下的表型功能，这是适应性辐射的教科书例子。其具体目的是(1)利用四种互补的基因组策略来综合识别具有遗传变异的候选增强子，(2)使用CRISPR-Cas9来量化调节增强子活性的表型和转录效应，以及(3)经验地评估遗传变异对增强子活性的影响。这项工作将重点放在体内增强子在活性、转录调控和对表型的影响方面的功能效应，这项工作将解决关于基因-表型关系的一个主要知识空白。这些数据将为那些设计基因调控语法模型的人提供经验信息，显著加快非编码DNA因果遗传变异的发现和系统记录的框架，以及进化发育生物学核心理论(EVO-DEVO)的实验证据。该项目由iOS的发展系统集群和既定的刺激竞争研究计划(EPSCoR)联合资助。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Interactions among multiple selective pressures on the form–function relationship in insular stream fishes

多重选择压力对岛流鱼类形态与功能关系的相互作用

• DOI: 10.1093/biolinnean/blab098
• 发表时间: 2021
• 期刊: Biological Journal of the Linnean Society
• 影响因子: 1.9
• 作者: Diamond, Kelly M;Lagarde, Raphaël;Griner, J Gill;Ponton, Dominique;Powder, Kara E;Schoenfuss, Heiko L;Walker, Jeffrey A;Blob, Richard W
• 通讯作者: Blob, Richard W

Morphometric and Genetic Description of Trophic Adaptations in Cichlid Fishes.

• DOI: 10.3390/biology11081165
• 发表时间: 2022-08-03
• 期刊: Biology
• 影响因子: 4.2

Genetic basis of ecologically relevant body shape variation among four genera of cichlid fishes.

慈鲷四个属生态相关体形变异的遗传基础。

• DOI: 10.1111/mec.16977
• 发表时间: 2023
• 期刊: Molecular ecology
• 影响因子: 4.9
• 作者: DeLorenzo,Leah;Mathews,Destiny;Brandon,AAllyson;Joglekar,Mansi;CarmonaBaez,Aldo;Moore,EmilyC;Ciccotto,PatrickJ;Roberts,NatalieB;Roberts,ReadeB;Powder,KaraE
• 通讯作者: Powder,KaraE

Neural crest cells as a source of microevolutionary variation.

• DOI: 10.1016/j.semcdb.2022.06.001
• 发表时间: 2023-08
• 期刊: SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
• 影响因子: 7.3
• 作者: Brandon, A. Allyson;Almeida, Daniela;Powder, Kara E.
• 通讯作者: Powder, Kara E.