Escape from homeostasis
Escape from homeostasis
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DOI：
10.1016/j.mbs.2014.08.015
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发表时间：
2014-11-01
影响因子：
4.3
通讯作者：
Reed, Michael C.
中科院分区：
文献类型：
--
作者：
Nijhout, H. Frederik;Best, Janet;Reed, Michael C.
许多生理系统，从基因网络到生物化学再到整个生物体生理学，都表现出将某些变量保持在相当窄的范围内的动态平衡机制。由于动态平衡机制缓冲了环境和遗传变异对特征的影响，它们允许积累隐蔽的遗传变异。动态平衡机制从来不是完美的，可能会因为改变潜在机制的动力学的基因突变而变得不稳定。我们使用数学模型来研究五种不同的动态平衡机制：体温调节；同型半胱氨酸浓度的维持；前馈电路的神经控制；肾脏的生肌反应；以及大脑细胞外多巴胺水平的调节。在所有这些情况下，都有一些动态区对遗传或环境变异相对不敏感，两侧是对遗传或环境变化敏感的区域。此外，突变或环境变化会使个体更接近动态区的边缘，从而使该个体容易受到额外突变或环境变化造成的有害影响。突变和环境变量也可以减小动态区的大小，从而释放潜在的有害的隐蔽遗传变异。这些对突变、环境、动态平衡和逃避动态平衡的考虑有助于解释为什么这么多疾病的病因学是复杂的。(C)2014 Elsevier Inc.保留所有权利。
Many physiological systems, from gene networks to biochemistry to whole organism physiology, exhibit homeostatic mechanisms that keep certain variables within a fairly narrow range. Because homeostatic mechanisms buffer traits against environmental and genetic variation they allow the accumulation of cryptic genetic variation. Homeostatic mechanisms are never perfect and can be destabilized by mutations in genes that alter the kinetics of the underlying mechanism. We use mathematical models to study five diverse mechanisms of homeostasis: thermoregulation; maintenance of homocysteine concentration; neural control by a feed forward circuit; the myogenic response in the kidney; and regulation of extracellular dopamine levels in the brain. In all these cases there are homeostatic regions where the trait is relatively insensitive to genetic or environmental variation, flanked by regions where it is sensitive. Moreover, mutations or environmental changes can place an individual closer to the edge of the homeostatic region, thus predisposing that individual to deleterious effects caused by additional mutations or environmental changes. Mutations and environmental variables can also reduce the size of the homeostatic region, thus releasing potentially deleterious cryptic genetic variation. These considerations of mutations, environment, homeostasis, and escape from homeostasis help to explain why the etiology of so many diseases is complex. (C) 2014 Elsevier Inc. All rights reserved.