Animal tissue requires low-oxygen conditions for its maintenance. The need for low-oxygen conditions contrasts with the idea of an evolutionary leap in animal diversity as a result of expanding oxic conditions. To accommodate tissue renewal at oxic conditions, however, vertebrate animals and vascular plants demonstrate abilities to access hypoxia. Here, I argue that multicellular organisms sustain oxic conditions first after internalizing hypoxic conditions. The ‘harnessing’ of hypoxia has allowed multicellular evolution to leave niches that were stable in terms of oxygen concentrations for those where oxygen fluctuates. Since oxygen fluctuates in most settings on Earth's surface, the ancestral niche would have been a deep marine setting. The hypothesis that ‘large life’ depends on harnessing hypoxia is illustrated in the context of conditions that promote the immature cell phenotype (stemness) in animal physiology and tumour biology and offers one explanation for the general rarity of diverse multicellularity over most of Earth's history.

动物组织需要低氧条件来维持。对低氧条件的需求与由于含氧条件扩大而导致动物多样性进化飞跃的想法形成鲜明对比。然而，为了在有氧条件下适应组织更新，脊椎动物和维管植物表现出获得缺氧的能力。在这里，我认为多细胞生物在内化缺氧条件后首先维持有氧条件。缺氧的“驾驭”使多细胞进化能够为氧气波动的细胞留下氧气浓度稳定的生态位。由于氧气在地球表面的大多数环境中波动，祖先的生态位将是一个深海环境。