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，尽管它们在突破性的生物发现方面具有巨大的潜力。这项研究将表征来自两个不同谱系的诺氏鱼类的HOX簇，这些生物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。已知HOX基因复合体密切参与轴向模式和结构的形成，这些结构可能在一定程度上有助于南极鱼类的适应性进化。许多后生动物HOX聚类数据集随时可以用于比较，并且已经为要检查的物种建立了细菌人工染色体(BAC)文库：一种后生动物(Notothenia coriicep，黄腹岩鳕鱼)和一种渠道类(Chaenocephalus aceratus，Scotia Sea“gapehead”icefish)。所得到的数据集将被证明对于描绘那些在极端环境的适应性进化中具有作用的序列非常有用。该数据将允许鉴定真正的顺式调控(增强子)序列。此外，我们还将进行实验，以描述HOX簇中与调节造血谱系规范有关的假定的组织特异性增强子元件。这些实验背后的理论基础是这样一个事实，即其中一种鱼(银鱼)的红系程序已经完全被废除。因此，比较基因组学方法应该发现那些在银鱼谱系中丢失但在其他谱系中保留的序列。比较实验将在斑马鱼中进行，那里已经开发了一个强大的系统来研究早期血祖细胞的谱系特征。这项工作的更广泛的影响包括生成进化生物学家、发育生物学家和生理学家可以访问的大型、公开可用的基因组数据集。我们之前的各种原始脊椎动物(鲨鱼、比奇尔、河豚、斑马鱼、腔棘鱼)的HOX数据集已经被科学界反复使用/分析。这一结果还将对一个重要的生物现象--血液的发展--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为少数族裔本科生的研究性培训制定了计划。