Mechanism and evolution of hypoxia-tolerance in humans.
Mechanism and evolution of hypoxia-tolerance in humans.
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发表时间：
1998-04
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通讯作者：
Peter W. Hochachka
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作者：
Peter W. Hochachka
对生理学家来说，“适应”一词通常是指任何被认为是有利的特征；进化生物学家需要一个更严格的定义（将其限制在在选择中产生和维持的特征上）。根据他们的定义，许多生理特征可能仅仅反映了通过血统传递的遗传。在考虑对缺氧耐受性的进化时，我们研究了鳍足动物（两个优势群体，phocids和otariids，具有不同的潜水能力）和人类谱系在不同世代暴露于低压缺氧的问题（真正的适应与简单的遗传）。复杂生理系统进化的基本原理首先出现在对潜水反应的分析中。然后，我们分析了三种不同谱系的人类对低压缺氧的反应：低地人、安第斯原住民（克丘亚人）和喜马拉雅原住民（夏尔巴人）。在鳍状肢的例子中，我们发现了人类对缺氧反应的“保守”和“适应”生理特征。保守的字符明显占主导地位，数量太多，无法详细概述；三个例子是血红蛋白的氧亲和力，肌肉组织成不同类型的纤维，以及大脑几乎唯一偏爱葡萄糖作为燃料。最值得注意的是，我们还发现，在所有被调查的组织级别中，都存在“适应性强”的特征。在克查亚人和夏尔巴人的全身水平上，我们发现(i)最大有氧和无氧运动能力被下调，（ii）预期来自低地人的缺氧急性效应（弥补因缺氧而导致的能量不足，即巴斯德效应）被减弱，（iii）适应效应也被减弱。骨骼肌的生化行为与降低对糖酵解对能量供应的依赖一致，从而提高了每摩尔碳燃料所利用的ATP的产量。心脏适应似乎也依赖于化学计量效率的调整，提高每摩尔氧气消耗的ATP产量（通过优先使用葡萄糖而不是脂肪酸）。我们注意到的大多数生化和生理适应（急性和驯化反应）在夏尔巴人和克丘亚人身上是相似的。在人类大约三分之一的历史中，这两个谱系并没有共同的祖先，所以它们相似的生理特征可能是在人类历史上两个不同的时间和地点，作为缺氧防御适应而独立出现的。就像潜水动物的氧气管理能力进化到极低水平一样，人类缺氧耐受性的进化可以用两种（保守与适应）生理特征在不同人类谱系中如何组合以及这种组合如何随着世代而变化来描述。最近有证据表明，我们的物种是在“更冷、更干燥和更高”的条件下进化的，这表明这些适应可能代表了人类“祖先”的生理条件。
To physiologists, the term 'adaptation' usually refers to any trait that is considered advantageous; evolutionary biologists require a more rigorous definition (restricting it to traits arising and maintained under selection). By their definition, many physiological traits may merely reflect inheritance passed on through lineage. In considering the evolution of tolerance to reduced oxygen availability, we examined the issue (of true adaptations versus simple inheritance) in pinnipeds (the two dominant groups, phocids and otariids, with varying diving capacities) and in human lineages exposed for varying generational periods to hypobaric hypoxia. Basic principles of the evolution of complex physiological systems first emerged from an analysis of the diving response. We then analyzed human responses to hypobaric hypoxia in three different lineages: lowlanders, Andean natives (Quechuas) and Himalayan natives (Sherpas). As in the pinniped example, we found 'conservative' and 'adaptable' physiological characters involved in human responses to hypoxia. Conservative characters are clearly dominant and are too numerous to outline in detail; three examples are haemoglobin oxygen-affinities, the organization of muscle into different fibre types and the brain's almost exclusive preference for glucose as a fuel. Most notably, we also found evidence for 'adaptable' characters at all levels of organization examined. At the whole-body level in Quechuas and Sherpas, we found (i) that maximum aerobic and anaerobic exercise capacities were down-regulated, (ii) that the acute effect of hypoxia (making up the energy deficit due to oxygen lack; i.e. the Pasteur effect) expected from lowlanders was blunted, and (iii) that acclimation effects were also attenuated. The biochemical behaviour of skeletal muscles was consistent with lowered reliance on glycolytic contributions to energy supply, thus improving the yield of ATP per mole of carbon fuel utilized. Heart adaptations also seemed to rely upon stoichiometric efficiency adjustments, improving the yield of ATP per mole of oxygen consumed (by using glucose in preference to fatty acids). Most of the biochemical and physiological adaptations we noted (both as acute and as acclimation responses) were similar in Sherpas and Quechuas. These two lineages have not shared a common ancestor for approximately one-third of the history of our species, so it is possible that their similar physiological traits arose independently as hypoxia defence adaptations in two different times and places in our history. As in the evolution of exquisite capacities for management of oxygen down to vanishingly low levels in diving animals, the evolution of human hypoxia-tolerance can be described in terms of how two (conservative versus adaptable) categories of physiological characters are assembled in different human lineages and how the assembly changes through generational time. More recent evidence indicating that our species evolved under 'colder, drier and higher' conditions suggests that these adaptations may represent the 'ancestral' physiological condition for humans.