Evolutionary Fates of Hemoglobin and Heme Scavengers in White-blooded Antarctic Icefishes

这项工作将拓宽我们的知识和洞察力，了解伴随物种进化而来的遗传特征丢失或变化，以及在独特的与世隔绝和寒冷的南大洋内。正在研究的携氧系统和相关蛋白质对人类健康非常重要，本工作专门研究的两种蛋白质(结合珠蛋白和血凝素)在防止肾脏过量铁负荷方面起着至关重要的作用。因此，该项目有可能贡献对医学科学有价值的新见解。该项目还将推动NSF培养新一代科学家和向公众提供科学发现的目标。该项目的首席研究员是一位早期的职业科学家，他的职业发展将因该项目而得到加强。它还将支持几名本科生在分子生物学、蛋白质生物化学以及对独特的南极鱼类动物群和环境的欣赏方面的培训。该项目将有助于建立一个内容丰富的网站，向公众介绍南大洋鱼类的生物发现和科学史，通过该项目，研究人员将为一年一度的儿童科学博物馆极地活动做出贡献。尽管所有物种中通常不可缺少的呼吸蛋白--血红蛋白和某些物种中的肌红蛋白在进化中显著丧失，但南极冰鱼仍然茁壮成长。在过去的几十年里，研究主要集中在这些鱼类中血红素蛋白丢失和由此产生的代偿适应背后的机制，而这种丢失对支持蛋白基因和功能的进化影响仍然没有得到解决。这个项目研究了两个重要的伙伴蛋白，血红蛋白清除剂结合珠蛋白和血红素清除剂Hopexin(血红素基团是含铁的蛋白质功能基团，如血红蛋白和肌红蛋白)的进化命运。由于南极冰鱼的永久血红蛋白为零状态，特别是在血红蛋白和肌红蛋白双重为零的物种中，保存功能性结合珠蛋白似乎是不必要的，而且血红蛋白的作用可能会减弱。该项目试图解决这些支持蛋白的共同进化丢失或减少是否发生在冰鱼的血红蛋白特征消失的过程中，以及这种变化背后的分子机制。研究人员设想，寒冷和富氧的海洋环境是一系列选择压力放松的开始。最初，这将消除维持功能性携氧蛋白的需要，最终导致它们的永久性丧失。这些事件反过来会放松对支持系统网络的维护，导致额外的性状损失或变化。

This work will broaden our knowledge and insights into genetic trait loss or change accompanying species evolution in general as well as within the uniquely isolated and frigid Southern Ocean. The system of oxygen-carrying and related proteins being studied is very important to human health and the two proteins being specifically studied in this work (haptoglobin and hemopexin) have crucial roles in preventing excess iron loading in the kidneys. As such, the project has the potential to contribute novel insights that could be valuable to medical science. The project will also further the NSF goals of training new generations of scientists and of making scientific discoveries available to the general public. The lead principal investigator on the project is an early career scientist whose career development will be enhanced by this project. It will also support the training of several undergraduate students in molecular biology, protein biochemistry, and appreciation of the unique Antarctic fish fauna and environment. The project will contribute to a content-rich web site that will bring to the public the history of biological discoveries and sciences on fishes of the Southern Ocean and through this project the investigators will contribute to an annual polar event at a children's science museum. The Antarctic icefishes have thrived despite the striking evolutionary loss of the normally indispensable respiratory protein hemoglobin in all species and myoglobin in some. Studies over the past decades have predominately focused on the mechanisms behind hemoprotein losses and the resulting compensatory adaptations in these fish, while evolutionary impact of such losses on the supporting protein genes and functions has remained unaddressed. This project investigates the evolutionary fate of two important partner proteins, the hemoglobin scavenger haptoglobin and the heme scavenger hemopexin (heme groups are the iron-containing functional group of proteins such as hemoglobin and myoglobin). With the permanent hemoglobin-null state in Antarctic icefishes, and particularly in dual hemoglobin- and myoglobin-null species, the preservation of a functional haptoglobin would seem unessential and the role of hemopexin likely diminished. This project seeks to resolve whether co-evolutionary loss or reduction of these supporting proteins occurred with the extinction of the hemoglobin trait in the icefishes, and the molecular mechanisms underlying such changes. The investigators envisage the cold and oxygen rich marine environment as the start of a cascade of relaxation of selection pressures. Initially this would have obviated the need for maintaining functional oxygen carrying proteins, ultimately leading to their permanent loss. These events in turn would have relaxed the maintenance of the network of supporting systems, leading to additional trait loss or change.