Bapat Niraja V, Rajamani Sudha
Indian Institute of Science Education and Research (IISER), Dr. Homi Bhabha Road, Pashan, Pune, Maharashtra, 4110 008, India.
J Mol Evol. 2015 Oct;81(3-4):72-80. doi: 10.1007/s00239-015-9700-1. Epub 2015 Oct 6.
The widely acknowledged 'RNA world' theory pertains to how life might have chemically originated on early Earth. It presumes the existence of catalytic RNAs, which were also capable of storing and propagating genetic information. Substantial research has gone into understanding how enzyme-free reactions of nucleic acids might have led to the formation of such catalytic RNA polymers. However, most of these studies involved reactions that were performed in aqueous systems devoid of any "background" molecules. This scenario is not a true representation of the complex chemical environment that might have been prevalent on prebiotic Earth. In the present study, we analyzed the effect of co-solutes ("background" molecules) on the rate and accuracy of template-directed nonenzymatic replication of RNA, in a putative RNA world. Our results suggest that presence of co-solutes in the reaction affects the addition of purine monomers across their cognate template base. Reduction in the rate of these 'fast' cognate addition reactions resulted in an apparent increase in the frequency of mismatches in the presence of co-solutes. However, reactions that involved the addition of a mismatched base were not notably affected. Such a scenario could have led to an accrual of mutations during the propagation of functional sequences on early Earth, unless the relevant sequences were separated from the bulk reaction milieu by some limiting boundary structure (e.g., a membrane). In general, our results suggest that the presence of co-solutes could have affected certain prebiotic reaction rates to a larger extent than others. Even modest changes in nonenzymatic replication reaction rates could have eventually resulted in the accumulation of greater variation in RNA sequences over prolonged time periods. It, therefore, is pertinent to account for the chemical complexity intrinsic to prebiotic environments while studying relevant nonenzymatic reactions.
广为人知的“RNA世界”理论涉及生命在早期地球上可能如何通过化学方式起源。它假定存在催化性RNA，这种RNA还能够存储和传播遗传信息。人们已经进行了大量研究，以了解核酸的无酶反应如何可能导致形成这种催化性RNA聚合物。然而，这些研究大多涉及在没有任何“背景”分子的水性体系中进行的反应。这种情况并不能真实反映前生物地球可能普遍存在的复杂化学环境。在本研究中，我们分析了共溶质（“背景”分子）对假定的RNA世界中RNA模板导向的非酶复制的速率和准确性的影响。我们的结果表明，反应中共溶质的存在会影响嘌呤单体跨其同源模板碱基的添加。这些“快速”同源添加反应速率的降低导致在共溶质存在下错配频率明显增加。然而，涉及添加错配碱基的反应并未受到显著影响。除非相关序列通过某种限制边界结构（例如膜）与大量反应环境分离，否则这种情况可能导致早期地球上功能序列传播过程中出现突变累积。总体而言，我们的结果表明，共溶质的存在可能比其他因素对某些前生物反应速率的影响更大。即使非酶复制反应速率的适度变化最终也可能导致RNA序列在较长时间内积累更大的变异。因此，在研究相关的非酶反应时，考虑前生物环境固有的化学复杂性是很有必要的。
