MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, UK.
Department of Physical and Quantum Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wrocław, Poland.
Nature. 2020 Jun;582(7810):60-66. doi: 10.1038/s41586-020-2330-9. Epub 2020 Jun 3.
The nature of the first genetic polymer is the subject of major debate. Although the 'RNA world' theory suggests that RNA was the first replicable information carrier of the prebiotic era-that is, prior to the dawn of life-other evidence implies that life may have started with a heterogeneous nucleic acid genetic system that included both RNA and DNA. Such a theory streamlines the eventual 'genetic takeover' of homogeneous DNA from RNA as the principal information-storage molecule, but requires a selective abiotic synthesis of both RNA and DNA building blocks in the same local primordial geochemical scenario. Here we demonstrate a high-yielding, completely stereo-, regio- and furanosyl-selective prebiotic synthesis of the purine deoxyribonucleosides: deoxyadenosine and deoxyinosine. Our synthesis uses key intermediates in the prebiotic synthesis of the canonical pyrimidine ribonucleosides (cytidine and uridine), and we show that, once generated, the pyrimidines persist throughout the synthesis of the purine deoxyribonucleosides, leading to a mixture of deoxyadenosine, deoxyinosine, cytidine and uridine. These results support the notion that purine deoxyribonucleosides and pyrimidine ribonucleosides may have coexisted before the emergence of life.
第一个遗传聚合物的本质是一个主要的争论点。尽管“RNA 世界”理论表明，在生命出现之前的前生物时代，RNA 是第一个可复制的信息载体，但其他证据表明，生命可能始于一种异质的核酸遗传系统，其中包括 RNA 和 DNA。这种理论简化了最终从 RNA 作为主要信息存储分子到同质 DNA 的“遗传接管”，但需要在相同的局部原始地球化学情景中，对 RNA 和 DNA 构建块进行选择性的非生物合成。在这里，我们展示了一种高产、完全立体、区域和呋喃选择性的前生物嘧啶核糖核苷（胞苷和尿苷）合成方法。我们的合成使用了前生物嘧啶核糖核苷（胞苷和尿苷）合成中的关键中间体，并且我们表明，一旦生成，嘧啶就会在嘌呤脱氧核糖核苷的整个合成过程中持续存在，导致脱氧腺苷、脱氧肌苷、胞苷和尿苷的混合物。这些结果支持了这样一种观点，即在生命出现之前，嘌呤脱氧核糖核苷和嘧啶核糖核苷可能已经共存。
