Genomic Instability and the Evolution of the Antarctic Notothenioid Fishes

南极诺托类鱼类的基因组不稳定性和进化

• 批准号: 0336932
• 负责人: Harry Detrich
• 金额: $ 44万
• 依托单位: Northeastern University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-10-01 至 2007-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0336932&HistoricalAwards=false
• 关键词: Genomic; Instability; Evolution; Antarctic; Notothenioid

The ancestral Notothenioid fish stock of Antarctica probably arose as a sluggish, bottom-dwelling species that evolved some 40-60 million years ago in the then temperate shelf waters of the Antarctic continent. The grounding of the ice sheet on the continental shelf and changing trophic conditions may have eliminated the taxonomically diverse late Eocene fauna and initiated the rapid diversification of the Notothenioids. On the High Antarctic shelf, Notothenioids today dominate the fish fauna and are recognized as one of the few examples of a species flock of marine fishes. Recent work conducted by this investigator and others suggests strongly that evolutionary change at the level of the genome permeates the Notothenioids and perhaps has been a major driver of the rapid diversification of this suborder of bony fishes. One striking example is the loss by the icefishes (Channichthyidae) of the ability to produce functional erythrocytes and hemoglobin. This natural "knockout" of the erythroid lineage makes the icefish taxon a unique genetic resource for analyzing the signaling pathways and transcriptional machinery involved in erythroid determination and differentiation. The hemoglobin-null and erythrocyte-null phenotypes appear to have been caused, at least in part, by genomic rearrangements and/or deletions mediated by repetitive elements and retrotransposons. One objective of this proposal will be to evaluate the role of genome instability in the evolution of the hematopoietic program of the icefishes. Using fluorescence in situ hybridization-based cytogenetics and bacterial artificial chromosome (BAC) libraries,erythropoietic gene loci will be mapped physically to the genomes of two notothenioids, the red-blooded rockcod Notothenia coriiceps and the white-blooded icefish Chaenocephalus aceratus, to determine the patterns of gene retention, inactivation, and/or loss that cause the erythrocyte-null condition. A second objective will be to exploit the absence of erythrocytes in icefishes to discover novel genes involved in the erythropoietic genetic program by use of new comparative genomic technologies. A third objective will be to determine the functions of newly discovered erythroid genes and their encoded proteins by functional analysis of zebrafish orthologs in zebrafish embryos. In summary, this research will evaluate the evolutionary mechanisms that generated the novel erythropoietic phenotype of the Antarctic icefishes and will exploit this novel taxon to conduct an unbiased, genome-wide scan for genes involved in red cell formation. The broader impacts include graduate student training in genomic molecular biology, including the bioinformatic strategies necessary to mine the data set for the potential functions of novel erythroid genes, and the use of a model system, the zebrafish, to test the hypothetical functions of these genes. A Web-hosted database will be created so that other laboratories can make use of the genome mapping data generated by this research project and lay audiences can learn about the uses of genomics for solving important questions in polar biology. In addition, the discovery of novel genes that participate in hematopoiesis may contribute important targets for the development by the biotechnology industry of therapeutics to treat anemias, leukemias, and other blood diseases.

南极洲的祖先Notothenioid鱼类种群可能是作为一种缓慢的、底栖物种出现的，大约4000万至6000万年前在南极大陆当时的温带大陆架沃茨进化而来。大陆架上冰盖的接地和不断变化的营养条件可能消除了分类学上多样的始新世晚期动物群，并开始了Notothenioids的快速多样化。在高南极大陆架，Notothenioids今天占主导地位的鱼类区系，并被认为是一个海洋鱼类种群的少数例子之一。最近的工作进行的调查员和其他人强烈表明，在基因组水平的进化变化渗透的Notothenioids，也许一直是一个主要的驱动力，这个亚目的硬骨鱼的快速多样化。一个突出的例子是冰鱼（鱼科）丧失了产生功能性红细胞和血红蛋白的能力。这种自然的“敲除”的红细胞谱系的冰鱼分类群的一个独特的遗传资源，用于分析的信号通路和转录机制参与红细胞的决定和分化。血红蛋白无效和红细胞无效表型似乎至少部分由重复元件和逆转录转座子介导的基因组重排和/或缺失引起。这项建议的一个目标是评估基因组不稳定性在冰鱼造血程序进化中的作用。使用荧光原位杂交为基础的细胞遗传学和细菌人工染色体（BAC）库，红细胞生成基因位点将物理映射到两个notothenioids，红血rockcod Notothenia coriiceps和白血冰鱼Chaenocephalus aceratus的基因组，以确定模式的基因保留，失活，和/或损失，导致红细胞无效的条件。第二个目标是利用冰鱼中红细胞的缺失，通过使用新的比较基因组技术发现红细胞生成遗传程序中涉及的新基因。第三个目标将是通过对斑马鱼胚胎中斑马鱼直系同源基因的功能分析来确定新发现的红细胞基因及其编码蛋白的功能。总之，本研究将评估产生新的红细胞生成表型的南极冰鱼的进化机制，并将利用这种新的分类进行公正的，全基因组扫描的基因参与红细胞形成。更广泛的影响包括对研究生进行基因组分子生物学培训，包括挖掘新红细胞基因潜在功能数据集所需的生物信息学策略，以及使用模型系统斑马鱼来测试这些基因的假设功能。将建立一个网络托管数据库，以便其他实验室可以利用该研究项目产生的基因组绘图数据，并使非专业观众可以了解基因组学在解决极地生物学重要问题方面的用途。此外，参与造血的新基因的发现可能为生物技术工业开发治疗贫血、白血病和其他血液疾病的疗法提供重要靶点。