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

这项工作将扩大我们对遗传性状丧失或伴随物种进化的变化的知识和见解，以及在独特的孤立和寒冷的南大洋。正在研究的携氧和相关蛋白质系统对人类健康非常重要，这项工作中专门研究的两种蛋白质（触珠蛋白和血红素结合蛋白）在防止肾脏中过量铁负荷方面具有至关重要的作用。因此，该项目有可能为医学科学提供有价值的新见解。该项目还将进一步推动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名早期职业科学家，他的职业发展将通过该项目得到加强。它还将支助对几名本科生进行分子生物学、蛋白质生物化学和了解南极独特的鱼类区系和环境方面的培训。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，调查人员将为儿童科学博物馆的年度极地活动作出贡献。尽管所有物种都失去了通常不可或缺的呼吸蛋白血红蛋白，有些物种失去了肌红蛋白，但南极冰鱼仍然蓬勃发展。在过去的几十年里，研究主要集中在血红素蛋白损失背后的机制和由此产生的补偿性适应这些鱼，而这种损失对支持蛋白基因和功能的进化影响仍然没有得到解决。该项目研究了两种重要的伴侣蛋白质的进化命运，血红蛋白清除剂触珠蛋白和血红素清除剂血红素结合蛋白（血红素基团是血红蛋白和肌红蛋白等蛋白质的含铁官能团）。随着永久血红蛋白空状态在南极冰鱼，特别是在双血红蛋白和肌红蛋白空物种，功能性触珠蛋白的保存似乎是不必要的，血红素结合蛋白的作用可能会减少。该项目旨在解决这些支持蛋白的共同进化损失或减少是否与冰鱼血红蛋白性状的灭绝有关，以及这些变化的分子机制。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，最终导致其永久丧失。这些事件反过来又会放松对支持系统网络的维护，导致额外的性状丧失或改变。

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.