Center for non-coding RNA in Technology and Health (RTH), University of Copenhagen, Denmark.
Department of Veterinary and Animal Sciences, University of Copenhagen, Denmark.
Nucleic Acids Res. 2022 Mar 21;50(5):2452-2463. doi: 10.1093/nar/gkac067.
Accelerated evolution of any portion of the genome is of significant interest, potentially signaling positive selection of phenotypic traits and adaptation. Accelerated evolution remains understudied for structured RNAs, despite the fact that an RNA's structure is often key to its function. RNA structures are typically characterized by compensatory (structure-preserving) basepair changes that are unexpected given the underlying sequence variation, i.e., they have evolved through negative selection on structure. We address the question of how fast the primary sequence of an RNA can change through evolution while conserving its structure. Specifically, we consider predicted and known structures in vertebrate genomes. After careful control of false discovery rates, we obtain 13 de novo structures (and three known Rfam structures) that we predict to have rapidly evolving sequences-defined as structures where the primary sequences of human and mouse have diverged at least twice as fast (1.5 times for Rfam) as nearby neutrally evolving sequences. Two of the three known structures function in translation inhibition related to infection and immune response. We conclude that rapid sequence divergence does not preclude RNA structure conservation in vertebrates, although these events are relatively rare.
基因组任何部分的加速进化都引起了人们的极大关注，这可能表明表型特征和适应的正选择。尽管 RNA 的结构通常是其功能的关键，但对于结构 RNA，加速进化的研究仍然不足。RNA 结构通常由补偿性（结构保存）碱基对变化来表征，这些变化与基础序列变异相比是出乎意料的，即它们是通过对结构的负选择而进化的。我们研究了在保持 RNA 结构的同时，其一级序列通过进化能多快发生变化的问题。具体来说，我们考虑了脊椎动物基因组中的预测和已知结构。在仔细控制假发现率后，我们获得了 13 个新结构（和三个已知的 Rfam 结构），我们预测这些结构的序列进化速度很快——与附近中性进化序列相比，人类和小鼠的一级序列的分歧速度至少快两倍（对于 Rfam 则快 1.5 倍）。这三个已知结构中的两个与感染和免疫反应相关的翻译抑制有关。我们的结论是，快速的序列分歧并不排除脊椎动物中 RNA 结构的保守性，尽管这些事件相对较少。
