Theory of Condensed Matter Group, Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE, UK.
Sainsbury Laboratory, University of Cambridge, Bateman Street, Cambridge CB2 1LR, UK.
J R Soc Interface. 2021 Oct;18(183):20210380. doi: 10.1098/rsif.2021.0380. Epub 2021 Oct 6.
Genotype-phenotype maps link genetic changes to their fitness effect and are thus an essential component of evolutionary models. The map between RNA sequences and their secondary structures is a key example and has applications in functional RNA evolution. For this map, the structural effect of substitutions is well understood, but models usually assume a constant sequence length and do not consider insertions or deletions. Here, we expand the sequence-structure map to include single nucleotide insertions and deletions by using the RNAshapes concept. To quantify the structural effect of insertions and deletions, we generalize existing definitions for robustness and non-neutral mutation probabilities. We find striking similarities between substitutions, deletions and insertions: robustness to substitutions is correlated with robustness to insertions and, for most structures, to deletions. In addition, frequent structural changes after substitutions also tend to be common for insertions and deletions. This is consistent with the connection between energetically suboptimal folds and possible structural transitions. The similarities observed hold both for genotypic and phenotypic robustness and mutation probabilities, i.e. for individual sequences and for averages over sequences with the same structure. Our results could have implications for the rate of neutral and non-neutral evolution.
基因型-表型图谱将遗传变化与其适应度效应联系起来，因此是进化模型的重要组成部分。RNA 序列与其二级结构之间的图谱就是一个关键示例，并且在功能 RNA 进化中有应用。对于这个图谱，取代的结构效应已经得到很好的理解，但模型通常假设序列长度不变，并且不考虑插入或缺失。在这里，我们通过使用 RNAshapes 概念将包括单核苷酸插入和缺失的序列-结构图谱扩展到包括单核苷酸插入和缺失。为了量化插入和缺失的结构效应，我们推广了现有用于稳健性和非中性突变概率的定义。我们发现替换、缺失和插入之间存在惊人的相似性：对替换的稳健性与对插入的稳健性相关，并且对于大多数结构与对缺失的稳健性相关。此外，替换后经常发生的结构变化也往往在插入和缺失中很常见。这与能量上非最优的折叠与可能的结构转变之间的联系是一致的。观察到的相似性既适用于基因型稳健性和表型稳健性，也适用于突变概率，即适用于单个序列和具有相同结构的序列平均值。我们的结果可能对中性和非中性进化的速度有影响。
