HOX Clusters, Hematopoiesis and Genome Enablement in the Antarctic Notothenoid Fishes

南极Notothenoid鱼类的HOX簇、造血和基因组启用

• 批准号: 0632527
• 负责人: Chris Amemiya
• 金额: $ 55万
• 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: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0632527&HistoricalAwards=false
• 关键词: HOX; Clusters; Hematopoiesis; Genome; Enablement

Genomic approaches have been greatly lacking in Antarctic species despite their tremendous potential for groundbreaking biological discovery. The research will characterize HOX clusters from two disparate lineages of notothenioid fishes, organisms whose evolutionary history and myriad anatomical and physiological adaptations provide a unique opportunity to study the genetics of adaptation to extreme environments. Hox gene complexes are known to be intimately involved in axial patterning and formation of structures that could have contributed, in part, to adaptive evolution of Antarctic fishes. Numerous metazoan HOX cluster datasets are readily available for comparison, and bacterial artificial chromosome (BAC) libraries have already been generated for the species to be examined: a nototheniid (Notothenia coriiceps, yellowbelly rockcod) and a channichthyid (Chaenocephalus aceratus, Scotia Sea "gapehead" icefish). The resulting datasets will prove extremely useful for delineating those sequences having a role in adaptive evolution to the extreme environment. The data will allow identification of bona fide cis-regulatory (enhancer) sequences. In addition, we will carry out experiments to delineate presumptive tissue-specific enhancer elements within the HOX clusters that are involved in regulating hematopoietic lineage specification. The rationale behind these experiments hinges on the fact that the erythroid program in one of these fishes (icefish) has been completely abrogated. Thus, the comparative genomics approach should uncover those sequences that have been lost in the icefish lineage but retained in other lineages. The comparative experiments will be conducted in the zebrafish where a robust system for studying early lineage specification of blood progenitors has been developed.The broader impacts of this work include generation of large, publicly available genomic datasets that will be accessible to evolutionary biologists, developmental biologists, and physiologists. Our previous HOX datasets from various primitive vertebrates (shark, bichir, pufferfish, zebrafish, coelacanth) have been used/analyzed repeatedly by the scientific community. The results will also have implications for an important biological phenomenon, the development of blood. Finally, the project will provide ample opportunities for graduate and undergraduate participation and training, and programs are already in place at the Benaroya Research Institute for research training of minority undergraduate students.

基因组方法在南极物种中一直非常缺乏，尽管它们具有巨大的开创性生物发现潜力。这项研究将表征来自两个不同谱系的notothenioid鱼类的HOX集群，这些鱼类的进化历史和无数的解剖和生理适应为研究适应极端环境的遗传学提供了独特的机会。众所周知，Hox基因复合体密切参与轴向图案和结构的形成，这可能在一定程度上促进了南极鱼类的适应性进化。许多后生动物HOX聚类数据集很容易进行比较，细菌人工染色体（BAC）库已经产生的物种进行检查：一个nototheniid（Notothenia coriiceps，黄腹岩鳕）和channichthyid（Chaenocephalus aceratus，斯科舍海“gapehead”冰鱼）。由此产生的数据集将被证明是非常有用的描绘这些序列具有适应性进化的极端环境中的作用。这些数据将允许鉴定真正的顺式调节（增强子）序列。此外，我们将进行实验，以描绘推定的组织特异性增强子元件内的HOX集群参与调节造血谱系规范。这些实验背后的基本原理取决于这样一个事实，即这些鱼类之一（冰鱼）的红细胞程序已经完全废除。 因此，比较基因组学的方法应该发现那些序列已经失去了在冰鱼血统，但保留在其他血统。比较实验将在斑马鱼中进行，在那里已经开发了一个强大的系统来研究血液祖细胞的早期谱系特化。这项工作的更广泛的影响包括生成大型的、公开可用的基因组数据集，这些数据集将被进化生物学家、发育生物学家和生理学家访问。我们以前从各种原始脊椎动物（鲨鱼，bichir，河豚，斑马鱼，腔棘鱼）的HOX数据集已被科学界反复使用/分析。 这些结果也将对一个重要的生物学现象--血液的发育--产生影响。 最后，该项目将为研究生和本科生的参与和培训提供充足的机会，贝纳罗亚研究所已经制定了少数民族本科生研究培训方案。