Stich Michael, Briones Carlos, Manrubia Susanna C
Centro de Astrobiología (INTA-CSIC), Instituto Nacional de Técnica Aeroespacial, Ctra de Ajalvir, Torrejón de Ardoz (Madrid), Spain.
BMC Evol Biol. 2007 Jul 9;7:110. doi: 10.1186/1471-2148-7-110.
RNA molecules, through their dual appearance as sequence and structure, represent a suitable model to study evolutionary properties of quasispecies. The essential ingredient in this model is the differentiation between genotype (molecular sequences which are affected by mutation) and phenotype (molecular structure, affected by selection). This framework allows a quantitative analysis of organizational properties of quasispecies as they adapt to different environments, such as their robustness, the effect of the degeneration of the sequence space, or the adaptation under different mutation rates and the error threshold associated.
We describe and analyze the structural properties of molecular quasispecies adapting to different environments both during the transient time before adaptation takes place and in the asymptotic state, once optimization has occurred. We observe a minimum in the adaptation time at values of the mutation rate relatively far from the phenotypic error threshold. Through the definition of a consensus structure, it is shown that the quasispecies retains relevant structural information in a distributed fashion even above the error threshold. This structural robustness depends on the precise shape of the secondary structure used as target of selection. Experimental results available for natural RNA populations are in qualitative agreement with our observations.
Adaptation time of molecular quasispecies to a given environment is optimized at values of the mutation rate well below the phenotypic error threshold. The optimal value results from a trade-off between diversity generation and fixation of advantageous mutants. The critical value of the mutation rate is a function not only of the sequence length, but also of the specific properties of the environment, in this case the selection pressure and the shape of the secondary structure used as target phenotype. Certain functional motifs of RNA secondary structure that withstand high mutation rates (as the ubiquitous hairpin motif) might appear early in evolution and be actually frozen evolutionary accidents.
RNA分子通过其作为序列和结构的双重表现形式，成为研究准种进化特性的合适模型。该模型的关键要素是基因型（受突变影响的分子序列）和表型（受选择影响的分子结构）之间的区分。这个框架允许对准种在适应不同环境时的组织特性进行定量分析，例如它们的稳健性、序列空间退化的影响，或在不同突变率及相关错误阈值下的适应性。
我们描述并分析了分子准种在适应发生前的过渡阶段以及适应发生后的渐近状态下适应不同环境时的结构特性。我们观察到，在突变率值相对远离表型错误阈值时，适应时间达到最小值。通过定义一种共有结构，结果表明即使在错误阈值之上，准种仍以分布式方式保留相关结构信息。这种结构稳健性取决于用作选择目标的二级结构的精确形状。天然RNA群体的实验结果与我们的观察结果在定性上一致。
分子准种对给定环境的适应时间在远低于表型错误阈值的突变率值时达到最优。最优值源于多样性产生与有利突变体固定之间的权衡。突变率的临界值不仅是序列长度的函数，也是环境特定属性的函数，在这种情况下是选择压力以及用作目标表型的二级结构的形状。某些能承受高突变率的RNA二级结构功能基序（如普遍存在的发夹基序）可能在进化早期出现，实际上是冻结的进化偶然事件。
