Aerobic capacity is a complex performance trait with important consequences for fitness, and is determined by the integrated function of the O₂ transport pathway. The components of the O₂ pathway interact and function as an integrated physiological system, which could strongly influence the contribution of each component to variation in aerobic capacity. In this commentary, we highlight the value of hierarchical reductionism – combining studies of how component parts work in isolation with studies of how components interact within integrated systems – for understanding the evolution of aerobic capacity. This is achieved by focussing on the role of haemoglobin in adaptive increases in aerobic capacity in high-altitude deer mice (Peromyscus maniculatus). High-altitude deer mice have evolved increased aerobic capacity in hypoxia, in association with evolved changes in several subordinate traits across the O₂ pathway. This includes an evolved increase in Hb-O₂ affinity – which helps safeguard arterial O₂ saturation in hypoxia – and reductionist approaches have been successful at identifying the genetic, structural, and biochemical underpinnings of variation in this trait. However, theoretical modelling and empirical measurements suggest that increased Hb-O₂ affinity may not augment aerobic capacity on its own. The adaptive benefit of increased Hb-O₂ affinity in high-altitude deer mice appears to have been contingent upon antecedent changes in other traits in the O₂ pathway, particularly an increased capacity for O₂ diffusion and utilization in active tissues. These findings highlight the importance of understanding the interactions between the components of integrated systems for fully appreciating the evolution of complex performance phenotypes.

有氧能力是一种复杂的表现特征，对健康有重要影响，由 O ₂运输途径的综合功能决定。O ₂途径的成分相互作用并作为一个完整的生理系统发挥作用，这可以强烈影响每个成分对有氧能力变化的贡献。在这篇评论中，我们强调了层次还原论的价值——将组件如何独立工作的研究与组件如何在集成系统内相互作用的研究相结合——对于理解有氧能力的演变。这是通过关注血红蛋白在高海拔鹿鼠（Peromyscus maniculatus）有氧能力适应性增加中的作用来实现的）。高海拔鹿鼠在缺氧条件下进化出更高的有氧能力，这与 O ₂通路中几个从属性状的进化变化有关。这包括 Hb-O ₂亲和力的进化增加- 这有助于保护缺氧时的动脉 O ₂饱和 - 并且还原论方法已成功地确定了该性状变异的遗传、结构和生化基础。然而，理论模型和经验测量表明，增加 Hb-O ₂亲和力本身可能不会增加有氧能力。增加 Hb-O ₂的适应性益处高海拔鹿鼠的亲和力似乎取决于 O ₂途径中其他性状的先前变化，特别是活性组织中O ₂扩散和利用的能力增加。这些发现强调了理解集成系统组件之间相互作用的重要性，以充分了解复杂性能表型的演变。