Szöllosi Gergely J, Derényi Imre
Eötvös University, Budapest, Hungary.
Mol Biol Evol. 2009 Apr;26(4):867-74. doi: 10.1093/molbev/msp008. Epub 2009 Jan 23.
Genetic robustness, the preservation of an optimal phenotype in the face of mutations, is critical to the understanding of evolution as phenotypically expressed genetic variation is the fuel of natural selection. The origin of genetic robustness, whether it evolves directly by natural selection or it is a correlated byproduct of other phenotypic traits, is, however, unresolved. Examining micro-RNA (miRNA) genes of several eukaryotic species, Borenstein and Ruppin (Borenstein E, Ruppin E. 2006. Direct evolution of genetic robustness in microRNA. Proc Natl Acad Sci USA. 103: 6593) showed that the structure of miRNA precursor stem loops exhibits significantly increased mutational robustness in comparison with a sample of random RNA sequences with the same stem-loop structure. The observed robustness was found to be uncorrelated with traditional measures of environmental robustness-implying that miRNA sequences show evidence of the direct evolution of genetic robustness. These findings are surprising as theoretical results indicate that the direct evolution of robustness requires high mutation rates and/or large effective population sizes only found among RNA viruses, not multicellular eukaryotes. We demonstrate that the sampling method used by Borenstein and Ruppin introduced significant bias that lead to an overestimation of robustness. Introducing a novel measure of environmental robustness based on the equilibrium thermodynamic ensemble of secondary structures of the miRNA precursor sequences, we demonstrate that the biophysics of RNA folding induces a high level of correlation between genetic (mutational) and environmental (thermodynamic) robustness, as expected from the theory of plastogenetic congruence introduced by Ancel and Fontana (Ancel LW, Fontana W. 2000. Plasticity, evolvability, and modularity in RNA. J Exp Zool. 288: 242-283). In light of theoretical considerations, we believe that this correlation strongly suggests that genetic robustness observed in miRNA sequences is the byproduct of selection for environmental robustness.
遗传稳健性，即在面对突变时对最优表型的维持，对于理解进化至关重要，因为表型表达的遗传变异是自然选择的动力。然而，遗传稳健性的起源，无论是直接通过自然选择进化而来，还是其他表型特征的相关副产品，仍未得到解决。通过研究几种真核生物的微小RNA（miRNA）基因，博伦斯坦和鲁平（博伦斯坦E，鲁平E。2006年。微小RNA中遗传稳健性的直接进化。美国国家科学院院刊。103：6593）表明，与具有相同茎环结构的随机RNA序列样本相比，miRNA前体茎环的结构表现出显著增强的突变稳健性。观察到的稳健性与传统的环境稳健性指标不相关，这意味着miRNA序列显示出遗传稳健性直接进化的证据。这些发现令人惊讶，因为理论结果表明，稳健性的直接进化需要高突变率和/或仅在RNA病毒而非多细胞真核生物中才有的大有效种群规模。我们证明，博伦斯坦和鲁平使用的采样方法引入了显著偏差，导致对稳健性的高估。基于miRNA前体序列二级结构的平衡热力学系综引入一种新的环境稳健性度量方法，我们证明RNA折叠的生物物理学在遗传（突变）稳健性和环境（热力学）稳健性之间诱导了高度相关性，正如安塞尔和丰塔纳提出的塑性遗传一致性理论所预期的那样（安塞尔LW，丰塔纳W。2000年。RNA的可塑性、进化能力和模块化。实验动物学杂志。288：242 - 283）。鉴于理论考量，我们认为这种相关性有力地表明，在miRNA序列中观察到的遗传稳健性是对环境稳健性选择的副产品。
