Evolutionary physiology of tissue oxygenation in mammals

氧气的使用是哺乳动物生命最基本的先决条件之一。然而，在它们如何将其输送到组织的细节上存在着显着的差异-我们对这种差异的理解存在严重的差距。本项目旨在解决这些未回答的问题。 哺乳动物在供氧机制方面表现出令人惊讶的高变异性，例如血氧亲和力、红细胞体积和离子调节、血红蛋白聚集趋势、视网膜和胎盘血管化模式以及成人与胎儿血红蛋白氧结合特性的差异。这些性状中的一些进一步与遗传多态性相关，并且对兽医和比较生理学家非常感兴趣。然而，其根本原因在很大程度上仍然无法解释。 该项目的目的是分析这些特征在时间校准的哺乳动物生殖发育中的分布和演变，以增加我们对可能塑造其当前生理多样性的因素的理解。利用最近的进步，我们的理解哺乳动物的进化关系和进化生物学的比较方法，一些可能的因素将进行评估，可能会支持所观察到的哺乳动物血液和组织供氧机制的差异。这些因素包括过去2.5亿年来大气中氧气水平的变化、亲子冲突、由于活动生活方式改变而导致的代谢率的进化变化、体重的缩放效应以及高海拔或地下生态位中氧气可用性的降低。其他特征，如改变红细胞离子组成和血红蛋白聚集倾向，可能是血液寄生虫防御的重复进化。 了解选择压力和形成哺乳动物供氧机制多样性的分子机制（从珠蛋白基因到哺乳动物群落）可能有助于确定适应未来环境变化的倾向和限制，这将直接影响生物多样性的动态。

Use of oxygen is one of the most fundamental prerequisites of mammalian life. Yet there is remarkable variation in the details of how they deliver it to their tissues - and there are serious gaps in our understanding of this variation. This project aims to address these unanswered questions. Mammals show a surprisingly high variability in oxygen supply mechanisms, such as differences in blood oxygen affinity, erythrocyte volume- and ion-regulation, haemoglobin aggregation tendency, retinal and placental vascularisation patterns, and adult versus foetal haemoglobin oxygen binding properties. Some of these traits are further linked to genetic polymorphisms and are of great interest to veterinarians and comparative physiologists. Yet their underlying causes have largely remained unexplained. The aim of this project is to analyse the distribution and trace the evolution of these traits on a time-calibrated mammalian phylogeny to increase our understanding of factors that may have shaped their current physiological diversity. Taking advantage of the recent improvements in our understanding of the evolutionary relationships of mammals and the comparative method in evolutionary biology, a number of possible factors will be assessed that may underpin the observed differences in mammalian blood and tissue oxygen supply mechanism. These factors include changes in atmospheric oxygen levels over the last 250 million years, parent-offspring conflict, evolutionary changes in metabolic rate due to altered activity life styles, scaling effects with body mass, and reduced oxygen availability in high-altitude or subterranean niches. Other traits, like altered erythrocyte ion compositions and haemoglobin aggregation tendency, may have repeatedly evolved for blood parasite defence. Understanding selection pressures and molecular mechanisms that have shaped the diversity of mammalian oxygen supply mechanisms (from globin genes to mammalian communities) may help identifying predispositions and constraints for adapting to future environmental change, which will directly affect the dynamics of biodiversity.