Plasticity, evolvability, and modularity in RNA
Plasticity, evolvability, and modularity in RNA
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DOI：
10.1002/1097-010x(20001015)288:3
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发表时间：
2000-10-15
影响因子：
--
通讯作者：
Fontana, W
中科院分区：
文献类型：
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作者：
Ancel, LW;Fontana, W
RNA从序列折叠成二级结构是基因型-表型图谱的一个简单而强大的生物药理学基础模型，其中可塑性、进化性、上位性和模块性等概念不仅可以精确定义和统计测量，而且还可以揭示自然选择的同时和深刻的非独立效应。分子可塑性在这里被看作是RNA序列通过在恒定温度下在它们之间平衡而呈现各种能量上有利的形状的能力。通过基于实验设计的模拟，我们研究了在恒定环境中朝着预定义的目标形状进化的RNA分子群体的动态。序列的可塑性库中的每个形状对序列的整体适应度的贡献与序列在该形状中花费的时间成比例。可塑性是昂贵的，因为序列可以呈现的形状越多，它在其中任何一个上花费的时间就越少。不出所料，选择导致可塑性的降低（环境渠化）。然而，最引人注目的观察结果是进化过程同时减慢并最终停止。可塑性的降低需要遗传渠道化，也就是说，变异性的急剧丧失（从而丧失进化性）达到锁定的程度。环境渠化和遗传渠化之间的因果桥梁是由一个序列的塑性库中的一组形状和其遗传邻域中的一组主导（最小自由能）形状之间的相关性提供的。RNA基因型-表型图的这种统计特性，我们称之为质体发生一致性，将种群困在大多数遗传变异是表型中性的区域。我们称这种现象为中性约束。中性限制的分析模型，由完美的质体发生一致性的假设，正式连接突变率，表型空间的地形，和可进化性。这些模型确定了三个突变制度：对应于中性限制，探索阈值对应于中性限制的崩溃与显性表型的同时持续存在，和一个经典的错误阈值对应于显性表型的损失。在最后一步中，我们分析了渠化表型的结构特性。可塑性的降低导致了极端的模块化，我们从几个角度进行分析：热物理（熔化-反应规范的RNA版本），动力学（折叠途径-发育的RNA版本）和遗传（转座性-对遗传背景的不敏感性）。该模型，从而表明一个可能的进化起源的模块化的副作用，环境渠化。J. Exp. Zool.（Mol. Dev. Evol.）288：242-283，2000. (C)2000 Wiley-Liss，Inc.
RNA folding from sequences into secondary structures is a simple yet powerful, biophysically grounded model of a genotype-phenotype map in which concepts like plasticity, evolvability, epistasis, and modularity can not only be precisely defined and statistically measured but also reveal simultaneous and profoundly non-independent effects of natural selection. Molecular plasticity is viewed here as the capacity of an RNA sequence to assume a variety of energetically favorable shapes by equilibrating among them at constant temperature. Through simulations based on experimental designs, we study the dynamics of a population of RNA molecules that evolve toward a predefined target shape in a constant environment. Each shape in the plastic repertoire of a sequence contributes to the overall fitness of the sequence in proportion to the Lime the sequence spends in that shape. Plasticity is costly since the more shapes a sequence can assume, the less time it spends in any one of them. Unsurprisingly, selection leads to a reduction of plasticity (environmental canalization). The most striking observation, however, is the simultaneous slow-down and eventual halting of the evolutionary process. The reduction of plasticity entails genetic canalization, that is, a dramatic loss of variability (and hence a loss of evolvability) to the point of lock-in. The causal bridge between environmental canalization and genetic canalization is provided by a correlation between the set of shapes in the plastic repertoire of a sequence and the set of dominant (minimum free energy) shapes in its genetic neighborhood. This statistical property of the RNA genotype-phenotype map, which we call plastogenetic congruence, traps populations in regions where most genetic variation is phenotypically neutral. We call this phenomenon neutral confinement. Analytical models of neutral confinement, made tractable by the assumption of perfect plastogenetic congruence, formally connect mutation rate, the topography of phenotype space, and evolvability. These models identify three mutational regimes: that corresponding to neutral confinement, an exploration threshold corresponding to a breakdown of neutral confinement with the simultaneous persistence of the dominant phenotype, and a classic error threshold corresponding to the loss of the dominant phenotype. In a final step, we analyze the structural properties of canalized phenotypes. The reduction of plasticity leads to extreme modularity, which we analyze from several perspectives: thermophysical (melting--the RNA version of a norm of reaction), kinetic (folding pathways--the RNA version of development), and genetic (transposability-the insensitivity to genetic context). The model thereby suggests a possible evolutionary origin of modularity as a side effect of environmental canalization. J. Exp. Zool. (Mol. Dev. Evol.) 288:242-283, 2000. (C) 2000 Wiley-Liss, Inc.