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首页> 美国卫生研究院文献>Life >The Hypothesis that the Genetic Code Originated in Coupled Synthesis of Proteins and the Evolutionary Predecessors of Nucleic Acids in Primitive Cells
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The Hypothesis that the Genetic Code Originated in Coupled Synthesis of Proteins and the Evolutionary Predecessors of Nucleic Acids in Primitive Cells

机译：遗传密码起源于蛋白质和原始细胞中核酸进化前体的合成的假设

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Although analysis of the genetic code has allowed explanations for its evolution to be proposed, little evidence exists in biochemistry and molecular biology to offer an explanation for the origin of the genetic code. In particular, two features of biology make the origin of the genetic code difficult to understand. First, nucleic acids are highly complicated polymers requiring numerous enzymes for biosynthesis. Secondly, proteins have a simple backbone with a set of 20 different amino acid side chains synthesized by a highly complicated ribosomal process in which mRNA sequences are read in triplets. Apparently, both nucleic acid and protein syntheses have extensive evolutionary histories. Supporting these processes is a complex metabolism and at the hub of metabolism are the carboxylic acid cycles. This paper advances the hypothesis that the earliest predecessor of the nucleic acids was a β-linked polyester made from malic acid, a highly conserved metabolite in the carboxylic acid cycles. In the β-linked polyester, the side chains are carboxylic acid groups capable of forming interstrand double hydrogen bonds. Evolution of the nucleic acids involved changes to the backbone and side chain of poly(β-d-malic acid). Conversion of the side chain carboxylic acid into a carboxamide or a longer side chain bearing a carboxamide group, allowed information polymers to form amide pairs between polyester chains. Aminoacylation of the hydroxyl groups of malic acid and its derivatives with simple amino acids such as glycine and alanine allowed coupling of polyester synthesis and protein synthesis. Use of polypeptides containing glycine and l-alanine for activation of two different monomers with either glycine or l-alanine allowed simple coded autocatalytic synthesis of polyesters and polypeptides and established the first genetic code. A primitive cell capable of supporting electron transport, thioester synthesis, reduction reactions, and synthesis of polyesters and polypeptides is proposed. The cell consists of an iron-sulfide particle enclosed by tholin, a heterogeneous organic material that is produced by Miller-Urey type experiments that simulate conditions on the early Earth. As the synthesis of nucleic acids evolved from β-linked polyesters, the singlet coding system for replication evolved into a four nucleotide/four amino acid process (AMP = aspartic acid, GMP = glycine, UMP = valine, CMP = alanine) and then into the triplet ribosomal process that permitted multiple copies of protein to be synthesized independent of replication. This hypothesis reconciles the “genetics first” and “metabolism first” approaches to the origin of life and explains why there are four bases in the genetic alphabet.
机译：尽管对遗传密码的分析允许提出对其进化的解释，但是在生物化学和分子生物学中几乎没有证据为遗传密码的起源提供解释。特别是生物学的两个特征使得遗传密码的起源难以理解。首先，核酸是高度复杂的聚合物，需要大量的酶才能进行生物合成。其次，蛋白质具有简单的骨架，该骨架具有通过高度复杂的核糖体过程合成的20个不同的氨基酸侧链，在核糖体过程中，三联体中读取了mRNA序列。显然，核酸和蛋白质合成都具有广泛的进化历史。支持这些过程的是复杂的新陈代谢，而新陈代谢的中心是羧酸循环。本文提出了这样的假说，即最早的核酸前体是由苹果酸制成的β-连接的聚酯，苹果酸是羧酸循环中高度保守的代谢产物。在β-连接的聚酯中，侧链是能够形成链间双氢键的羧酸基。核酸的进化涉及聚（β-d-苹果酸）的主链和侧链的改变。侧链羧酸转化为羧酰胺或带有羧酰胺基团的较长侧链使信息聚合物在聚酯链之间形成酰胺对。苹果酸及其衍生物的羟基与简单氨基酸如甘氨酸和丙氨酸的氨基酰化使得聚酯合成和蛋白质合成偶联。使用含有甘氨酸和1-丙氨酸的多肽以甘氨酸或1-丙氨酸激活两种不同的单体可以简单地编码聚酯和多肽的自动催化合成，并建立了第一个遗传密码。提出了一种能够支持电子传输，硫酯合成，还原反应以及聚酯和多肽合成的原始细胞。该电池由被tholin包裹的硫化铁颗粒组成，tholin是一种通过模拟早期地球条件的Miller-Urey型实验产生的异质有机材料。随着核酸合成从β-连接的聚酯演变而来，用于复制的单线态编码系统演变成四核苷酸/四氨基酸过程（AMP =天冬氨酸，GMP =甘氨酸，UMP =缬氨酸，CMP =丙氨酸），然后变成三重核糖体过程，使蛋白质的多个拷贝得以合成而与复制无关。这个假设调和了“遗传优先”和“新陈代谢优先”的方法与生命起源的关系，并解释了为什么遗传字母中有四个基础。

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