从核糖核苷酸、阿拉伯核苷酸和 2'-脱氧核苷酸的益生元混合物中出现 RNA 的模型。,Journal of the American Chemical Society

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从核糖核苷酸、阿拉伯核苷酸和 2'-脱氧核苷酸的益生元混合物中出现 RNA 的模型。
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2020-01-08 , DOI: 10.1021/jacs.9b11239
Seohyun Chris Kim _{1,

2} , Lijun Zhou _{1,

2} , Wen Zhang _{1,

2} , Derek K O'Flaherty _{1,

2} , Valeria Rondo-Brovetto _{1,

2} , Jack W Szostak _{1,

2}

Affiliation

核糖核苷酸的非生物合成被认为是 RNA 世界出现的重要一步。然而，核糖核苷酸的益生元合成很可能伴随着阿拉伯核苷酸、2'-脱氧核糖核苷酸和规范核苷酸的其他变体的同时合成。为了了解如何从这种复杂的混合物中产生相对均一的 RNA，我们检查了非酶模板导向引物延伸反应中阿拉伯糖核苷酸和 2'-脱氧核糖核苷酸的性质。我们表明，用活化的阿拉伯核苷酸进行非酶引物延伸的效率比用活化的核糖核苷酸低得多，而且一旦掺入阿拉伯核苷酸，持续的引物延伸就会受到强烈抑制。如前所述，2'-脱氧核糖核苷酸在引物延伸反应中的掺入效率也较低，但差异较小。核苷酸混合物的实验表明，核糖核苷酸和阿拉伯核苷酸的共存不会阻碍 RNA 模板的复制。此外，含有 2'-脱氧或阿拉伯核苷酸的嵌合寡核苷酸是 RNA 合成的有效模板。我们提出最初的遗传聚合物是由非模板聚合形成的随机序列嵌合寡核苷酸，但模板复制化学有利于 RNA 合成；多轮复制可能导致了主要由 RNA 组成的寡聚体库。核苷酸混合物的实验表明，核糖核苷酸和阿拉伯核苷酸的共存不会阻碍 RNA 模板的复制。此外，含有 2'-脱氧或阿拉伯核苷酸的嵌合寡核苷酸是 RNA 合成的有效模板。我们提出最初的遗传聚合物是由非模板聚合形成的随机序列嵌合寡核苷酸，但模板复制化学有利于 RNA 合成；多轮复制可能导致了主要由 RNA 组成的寡聚体库。核苷酸混合物的实验表明，核糖核苷酸和阿拉伯核苷酸的共存不会阻碍 RNA 模板的复制。此外，含有 2'-脱氧或阿拉伯核苷酸的嵌合寡核苷酸是 RNA 合成的有效模板。我们提出最初的遗传聚合物是通过无模板聚合形成的随机序列嵌合寡核苷酸，但模板复制化学有利于 RNA 合成；多轮复制可能导致了主要由 RNA 组成的寡聚体库。我们提出最初的遗传聚合物是由非模板聚合形成的随机序列嵌合寡核苷酸，但模板复制化学有利于 RNA 合成；多轮复制可能导致了主要由 RNA 组成的寡聚体库。我们提出最初的遗传聚合物是由非模板聚合形成的随机序列嵌合寡核苷酸，但模板复制化学有利于 RNA 合成；多轮复制可能导致了主要由 RNA 组成的寡聚体库。

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A model for the emergence of RNA from a prebiotically plausible mixture of ribonucleotides, arabinonucleotides and 2’-deoxynucleotides.

The abiotic synthesis of ribonucleotides is thought to have been an essential step toward the emergence of the RNA world. However, it is likely that the prebiotic synthesis of ribonucleotides was accompanied by the simultaneous synthesis of arabinonucleotides, 2′-deoxyribonucleotides, and other variations on the canonical nucleotides. In order to understand how relatively homogeneous RNA could have emerged from such complex mixtures, we have examined the properties of arabinonucleotides and 2′-deoxyribonucleotides in nonenzymatic template-directed primer extension reactions. We show that nonenzymatic primer extension with activated arabinonucleotides is much less efficient than with activated ribonucleotides, and furthermore that once an arabinonucleotide is incorporated, continued primer extension is strongly inhibited. As previously shown, 2′-deoxyribonucleotides are also less efficiently incorporated in primer extension reactions, but the difference is more modest. Experiments with mixtures of nucleotides suggest that the coexistence of ribo- and arabinonucleotides does not impede the copying of RNA templates. Moreover, chimeric oligoribonucleotides containing 2′-deoxy- or arabinonucleotides are effective templates for RNA synthesis. We propose that the initial genetic polymers were random sequence chimeric oligonucleotides formed by untemplated polymerization, but that template copying chemistry favored RNA synthesis; multiple rounds of replication may have led to pools of oligomers composed mainly of RNA.

更新日期：2020-01-08

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