Department of Chemistry and Biochemistry, University of California, San Diego, San Diego, California 92093, USA.
Astrobiology. 2012 Sep;12(9):884-91. doi: 10.1089/ast.2011.0789.
The transition from genomic ribonucleic acid (RNA) to deoxyribonucleic acid (DNA) in primitive cells may have created a selection pressure that refined the genetic alphabet, resulting from the global weakening of the N-glycosyl bonds. Hydrolytic rupture of these bonds, termed deglycosylation, leaves an abasic site that is the single greatest threat to the stability and integrity of genomic DNA. The rates of deglycosylation are highly dependent on the identity of the nucleobases. Modifications made to the bases, such as deamination, oxidation, and alkylation, can further increase deglycosylation reaction rates, suggesting that the native bases provide optimum N-glycosyl bond stability. To protect their genomes, cells have evolved highly specific enzymes called glycosylases, associated with DNA repair, that detect and remove these damaged bases. In RNA, however, the occurrence of many of these modified bases is deliberate. The dichotomous behavior that cells exhibit toward base modifications may have originated in the RNA world. Modified bases would have been advantageous for the functional and structural repertoire of catalytic RNAs. Yet in an early DNA world, the utility of these heterocycles was greatly diminished, and their presence posed a distinct liability to the stability of cells' genomes. A natural selection for bases exhibiting the greatest resistance to deglycosylation would have ensured the viability of early DNA life, along with the recruitment of DNA repair.
原始细胞中从基因组核糖核酸（RNA）向脱氧核糖核酸（DNA）的转变，可能由于 N-糖苷键的整体弱化，产生了选择压力，从而使遗传密码得到了进一步优化。这些键的水解断裂，即去糖基化，会留下一个无碱基位点，这是对基因组 DNA 稳定性和完整性的最大威胁。去糖基化的速率高度依赖于核碱基的特性。碱基的修饰，如脱氨、氧化和烷基化，会进一步提高去糖基化反应速率，这表明天然碱基为 N-糖苷键提供了最佳稳定性。为了保护它们的基因组，细胞已经进化出高度特异性的酶，称为糖苷酶，它们与 DNA 修复有关，能够检测和去除这些受损的碱基。然而，在 RNA 中，许多这样的修饰碱基的出现是有意为之的。细胞对碱基修饰所表现出的二分法行为可能起源于 RNA 世界。修饰碱基对于催化 RNA 的功能和结构多样性是有利的。然而，在早期的 DNA 世界中，这些杂环的用途大大减少，它们的存在对细胞基因组的稳定性构成了明显的威胁。对表现出最大抗去糖基化能力的碱基的自然选择，将确保早期 DNA 生命的存活，并招募 DNA 修复。
