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脱氧核糖核苷酸对核酶的抑制作用与DNA的起源

Inhibition of ribozymes by deoxyribonucleotides and the origin of DNA.

作者信息

León P E

机构信息

School of Medicine and Cell and Molecular Biology Research Center (CIBCM), Universidad de Costa Rica, San José, Costa Rica.

出版信息

J Mol Evol. 1998 Aug;47(2):122-6. doi: 10.1007/pl00006368.

DOI:10.1007/pl00006368
PMID:9694660
Abstract

Two catalytic functions were required, minimally, for the appearance of DNA in evolution: a ribonucleotide reductase (RNR) and a reverse transcriptase (RT). If one accepts the explanatory strength of the RNA world model, it is clear that DNA molecules arose in the RNA world at some stage during the early evolution of cells. I suggest that competition for limited and valuable resources such as nucleotides, amino acids, and sugars made an early appearance among RNA cells, RNA viruses, viroids, and RNA plasmids. Structural and functional similarities between the different types of polymerases favor the simple hypothesis that the first RTs were RNA polymerase mutants that preferentially joined together preexisting deoxyribonucleotide triphosphates (dNTPs) using RNA templates. What was the role of dNTPs inside cells before DNA was synthesized and tested by natural selection? The oxygen atom that is removed by the reductase is of crucial importance to many ribozyme functions, since the 2'-OH is a strong nucleophile that forms transitional states during catalysis. Consequently, a RNR may have been used by cellular parasites to inhibit ribozyme action. Thus, DNA may have been, initially, an inert by-product of retrotranscription in lineages that acquired RTs and could synthesize DNA molecules using cellular RNA templates to detoxify the intracellular environment. DNA was useless as template until a transcriptase (DNA-dependent RNA polymerase) evolved that could copy (-)DNA to reconstitute the (+)RNA genome, indeed a successful way of confronting ribonuclease threats in the RNA world.

摘要

在进化过程中,DNA的出现至少需要两种催化功能:核糖核苷酸还原酶(RNR)和逆转录酶(RT)。如果接受RNA世界模型的解释力,那么很明显,DNA分子是在细胞早期进化的某个阶段在RNA世界中出现的。我认为,对核苷酸、氨基酸和糖类等有限且有价值资源的竞争在RNA细胞、RNA病毒、类病毒和RNA质粒中很早就出现了。不同类型聚合酶之间的结构和功能相似性支持了这样一个简单的假设,即最初的逆转录酶是RNA聚合酶突变体,它们优先利用RNA模板将预先存在的脱氧核糖核苷酸三磷酸(dNTP)连接在一起。在DNA通过自然选择被合成和测试之前,dNTP在细胞内起什么作用?还原酶去除的氧原子对许多核酶功能至关重要,因为2'-OH是一种强亲核试剂,在催化过程中形成过渡态。因此,细胞内寄生虫可能利用核糖核苷酸还原酶来抑制核酶的作用。因此,DNA最初可能是在获得逆转录酶并能够利用细胞RNA模板合成DNA分子以解毒细胞内环境的谱系中逆转录的惰性副产物。在转录酶(依赖DNA的RNA聚合酶)进化出来之前,DNA作为模板是无用的,转录酶可以复制(-)DNA以重建(+)RNA基因组,这确实是在RNA世界中应对核糖核酸酶威胁的一种成功方式。

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