Limits of adaptation: the evolution of selective neutrality.
Limits of adaptation: the evolution of selective neutrality.
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DOI：
10.1093/genetics/111.3.655
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发表时间：
1985-11
期刊：
影响因子：
3.3
通讯作者：
D. Hartl;D. Dykhuizen;A. Dean;A. Dean
中科院分区：
文献类型：
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作者：
D. Hartl;D. Dykhuizen;A. Dean;A. Dean
中间代谢中的许多酶表现出饱和动力学，其中通量是酶活性的凹函数，并且通常是Michaelis-Menten形式。其结果是，当自然选择倾向于增加酶的活性以使通量最大化时，就会达到收益递减点，在这个点上，通量的任何增加都会导致适应性的不成比例的小增加。酶活性最终将达到一定水平，在该水平下，活性增加的有利效果为1/（4 Ne）或更小，其中Ne是有效群体数。在这一点上，许多导致活性微小变化的突变将导致适应性的变化可以忽略不计，并且将选择性地接近中性。我们认为，这一过程是一种机制，通过这种机制，自然选择的长期持续作用可以为近中性突变和基因替换的发生创造条件。该假说的证据来自代谢理论、通量的直接研究、黑腹果蝇中的无效等位基因和其他类型等位基因的研究以及大肠杆菌恒化器的研究。该理论的局限性和复杂性包括环境或遗传背景的变化，具有明确定义的最佳活性的酶，超显性，多效性，多功能酶和分支代谢途径。我们的结论是，该理论是一个有用的综合，团结了许多看似无关的意见。主要的理论结论是，中性进化发生的条件可以作为自然选择作用的间接结果而产生。
Many enzymes in intermediary metabolism manifest saturation kinetics in which flux is a concave function of enzyme activity and often of the Michaelis-Menten form. The result is that, when natural selection favors increased enzyme activity so as to maximize flux, a point of diminishing returns will be attained in which any increase in flux results in a disproportionately small increase in fitness. Enzyme activity ultimately will reach a level at which the favorable effect of an increase in activity is of the order 1/(4Ne) or smaller, where Ne is the effective population number. At this point, many mutations that result in small changes in activity will result in negligible changes in fitness and will be selectively nearly neutral. We propose that this process is a mechanism whereby conditions for the occurrence of nearly neutral mutations and gene substitutions can be brought about by the long-continued action of natural selection. Evidence for the hypothesis derives from metabolic theory, direct studies of flux, studies of null and other types of alleles in Drosophila melanogaster and chemostat studies in Escherichia coli. Limitations and complications of the theory include changes in environment or genetic background, enzymes with sharply defined optima of activity, overdominance, pleiotropy, multifunctional enzymes and branched metabolic pathways. We conclude that the theory is a useful synthesis that unites many seemingly unrelated observations. The principal theoretical conclusion is that the conditions for the occurrence of neutral evolution can be brought about as an indirect result of the action of natural selection.