Reader John S, Joyce Gerald F
Department of Chemistry, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Nature. 2002;420(6917):841-4. doi: 10.1038/nature01185.
RNA molecules are thought to have been prominent in the early history of life on Earth because of their ability both to encode genetic information and to exhibit catalytic function. The modern genetic alphabet relies on two sets of complementary base pairs to store genetic information. However, owing to the chemical instability of cytosine, which readily deaminates to uracil, a primitive genetic system composed of the bases A, U, G and C may have been difficult to establish. It has been suggested that the first genetic material instead contained only a single base-pairing unit. Here we show that binary informational macromolecules, containing only two different nucleotide subunits, can act as catalysts. In vitro evolution was used to obtain ligase ribozymes composed of only 2,6-diaminopurine and uracil nucleotides, which catalyse the template-directed joining of two RNA molecules, one bearing a 5'-triphosphate and the other a 3'-hydroxyl. The active conformation of the fastest isolated ribozyme had a catalytic rate that was about 36,000-fold faster than the uncatalysed rate of reaction. This ribozyme is specific for the formation of biologically relevant 3',5'-phosphodiester linkages.
RNA分子被认为在地球生命早期历史中占据显著地位，因为它们既能编码遗传信息又能展现催化功能。现代遗传字母表依靠两组互补碱基对来存储遗传信息。然而，由于胞嘧啶的化学不稳定性，它容易脱氨基变成尿嘧啶，因此由A、U、G和C碱基组成的原始遗传系统可能难以建立。有人提出，最初的遗传物质可能仅包含单个碱基配对单元。在此我们表明，仅由两个不同核苷酸亚基组成的二元信息大分子可以充当催化剂。利用体外进化获得了仅由2,6 - 二氨基嘌呤和尿嘧啶核苷酸组成的连接酶核酶，它能催化两个RNA分子的模板导向连接，其中一个带有5'-三磷酸，另一个带有3'-羟基。分离出的最快核酶的活性构象，其催化速率比无催化反应速率快约36000倍。这种核酶对形成生物学相关的3',5'-磷酸二酯键具有特异性。
