Centro de Astrobiología (CSIC-INTA), Ctra de Ajalvir km 4, 28850 Torrejón de Ardoz, Madrid, Spain.
J Theor Biol. 2011 Jul 7;280(1):117-26. doi: 10.1016/j.jtbi.2011.03.010. Epub 2011 Mar 21.
RNA molecules, through their dual identity as sequence and structure, are an appropriate experimental and theoretical model to study the genotype-phenotype map and evolutionary processes taking place in simple replicator populations. In this computational study, we relate properties of the sequence-structure map, in particular the abundance of a given secondary structure in a random pool, with the number of replicative events that an initially random population of sequences needs to find that structure through mutation and selection. For common structures, this search process turns out to be much faster than for rare structures. Furthermore, search and fixation processes are more efficient in a wider range of mutation rates for common structures, thus indicating that evolvability of RNA populations is not simply determined by abundance. We also find significant differences in the search and fixation processes for structures of same abundance, and relate them with the number of base pairs forming the structure. Moreover, the influence of the nucleotide content of the RNA sequences on the search process is studied. Our results advance in the understanding of the distribution and attainability of RNA secondary structures. They hint at the fact that, beyond sequence length and sequence-to-function redundancy, the mutation rate that permits localization and fixation of a given phenotype strongly depends on its relative abundance and global, in general non-uniform, distribution in sequence space.
RNA 分子通过其序列和结构的双重身份,是研究简单复制子群体中发生的基因型-表型图谱和进化过程的合适实验和理论模型。在这项计算研究中,我们将序列-结构图谱的性质(特别是给定二级结构在随机池中出现的频率)与最初随机序列群体通过突变和选择找到该结构所需的复制事件数量联系起来。对于常见结构,这种搜索过程比稀有结构快得多。此外,常见结构的搜索和固定过程在更广泛的突变率范围内更有效,这表明 RNA 群体的可进化性不仅仅取决于丰度。我们还发现了相同丰度结构的搜索和固定过程中的显著差异,并将其与形成结构的碱基对数量联系起来。此外,还研究了 RNA 序列核苷酸含量对搜索过程的影响。我们的结果推进了对 RNA 二级结构分布和可达性的理解。它们暗示了这样一个事实,即除了序列长度和序列到功能的冗余之外,允许定位和固定给定表型的突变率强烈取决于其相对丰度以及序列空间中的全局、通常非均匀分布。