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

尽管南极物种具有突破性生物学发现的巨大潜力，但它们的基因组方法却非常缺乏。该研究将从两个不同的南极鱼谱系中描述HOX集群，这些生物的进化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基因复合物与轴向模式和结构的形成密切相关，这些结构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聚类数据集可供比较，细菌人工染色体（BAC）文库已经为待检测的物种生成：一种nototheniid （Notothenia coriiceps，黄腹岩鳕）和一种channichthyid （Chaenocephalus aceratus， Scotia海“裂口”冰鱼）。由此产生的数据集将被证明对描述那些在极端环境的适应性进化中起作用的序列非常有用。这些数据将允许鉴定真正的顺式调控（增强子）序列。此外，我们将进行实验来描述HOX集群中参与调节造血谱系规范的推定组织特异性增强子元件。这些实验背后的基本原理取决于这样一个事实，即其中一种鱼类（冰鱼）的红细胞程序已被完全废除。因此，比较基因组学方法应该揭示那些在冰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，在斑马鱼中已经建立了一个研究血液祖细胞早期谱系规范的健全系统。这项工作更广泛的影响包括生成大型的、公开可用的基因组数据集，这些数据集将供进化生物学家、发育生物学家和生理学家使用。我们以前的HOX数据集来自各种原始脊椎动物（鲨鱼，bichir，河豚，斑马鱼，腔棘鱼）已经被科学界反复使用/分析。研究结果还将对一个重要的生物现象——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为少数民族本科生提供了研究培训项目。

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.