Technical University of Denmark, DTU Chemistry, DK 2800 Kongens Lyngby, Denmark.
Comp Biochem Physiol A Mol Integr Physiol. 2013 Jan;164(1):119-28. doi: 10.1016/j.cbpa.2012.10.010. Epub 2012 Oct 18.
This paper presents an integrated model of convective O(2)-transport, aerobic dive limits (ADL), and thermochemical data for oxygen binding to mutant myoglobin (Mb), used to quantify the impact of mutations in Mb on the dive limits of Weddell seals (Leptonychotes weddellii). We find that wild-type Mb traits are only superior under specific behavioral and physiological conditions that critically prolong the ADL, action radius, and fitness of the seals. As an extreme example, the mutations in the conserved His-64 reduce ADL up to 14±2min for routine aerobic dives, whereas many other mutations are nearly neutral in terms of ADL and the inferred fitness. We also find that the cardiac system, the muscle O(2)-store, animal behavior (i.e. pre-dive ventilation), and the oxygen binding affinity of Mb, K(O(2)), have co-evolved to optimize dive duration at routine aerobic diving conditions, suggesting that such conditions are mostly selected upon in seals. The model is capable of roughly quantifying the physiological impact of single-protein mutations and thus bridges an important gap between animal physiology and molecular (protein) evolution.
本文提出了一个对流 O(2)-输运、有氧潜水极限 (ADL) 和氧结合突变肌红蛋白 (Mb) 热化学数据的综合模型，用于量化 Mb 突变对威德尔海豹 (Leptonychotes weddellii) 潜水极限的影响。我们发现，野生型 Mb 特征仅在特定的行为和生理条件下具有优势，这些条件极大地延长了 ADL、作用半径和海豹的适应度。作为一个极端的例子，保守的 His-64 突变将 ADL 减少多达 14±2min，用于常规的有氧潜水，而许多其他突变在 ADL 和推断的适应度方面几乎是中性的。我们还发现，心脏系统、肌肉 O(2)-储存、动物行为（即潜水前通气）和 Mb 的氧结合亲和力 K(O(2))，共同进化以优化常规有氧潜水条件下的潜水持续时间，这表明这些条件在海豹中主要受到选择。该模型能够大致量化单个蛋白质突变的生理影响，从而在动物生理学和分子（蛋白质）进化之间架起了一座重要的桥梁。
