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The Genetic Code and RNA-Amino Acid Affinities.

ABSTRACT: A significant part of the genetic code likely originated via a chemical interaction, which should be experimentally verifiable. One possible verification relates bound amino acids (or perhaps their activated congeners) and ribonucleotide sequences within cognate RNA binding sites. To introduce this interaction, I first summarize how amino acids function as targets for RNA binding. Then the experimental method for selecting relevant RNA binding sites is characterized. The selection method's characteristics are related to the investigation of the RNA binding site model treated at the outset. Finally, real binding sites from selection and also from extant natural RNAs (for example, the Sulfobacillus guanidinium riboswitch) are connected to the genetic code, and by extension, to the evolutionary progression that produced the code. During this process, peptides may have been produced directly on an instructive amino acid binding RNA (a DRT; Direct RNA Template). Combination of observed stereochemical selectivity with adaptation and co-evolutionary refinement is logically required, and also potentially sufficient, to create the striking order conserved throughout the present coding table.

SUBMITTER: Yarus M

PROVIDER: S-EPMC5492135 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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The Genetic Code and RNA-Amino Acid Affinities.

Yarus Michael M

Life (Basel, Switzerland) 20170323 2

A significant part of the genetic code likely originated via a chemical interaction, which should be experimentally verifiable. One possible verification relates bound amino acids (or perhaps their activated congeners) and ribonucleotide sequences within cognate RNA binding sites. To introduce this interaction, I first summarize how amino acids function as targets for RNA binding. Then the experimental method for selecting relevant RNA binding sites is characterized. The selection method's chara ...[more]

PMID: 28333103

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Project description:There is evidence that the genetic code was established prior to the existence of proteins, when metabolism was powered by ribozymes. Also, early proto-organisms had to rely on simple anaerobic bioenergetic processes. In this work I propose that amino acid fermentation powered metabolism in the RNA world, and that this was facilitated by proto-adapters, the precursors of the tRNAs. Amino acids were used as carbon sources rather than as catalytic or structural elements. In modern bacteria, amino acid fermentation is known as the Stickland reaction. This pathway involves two amino acids: the first undergoes oxidative deamination, and the second acts as an electron acceptor through reductive deamination. This redox reaction results in two keto acids that are employed to synthesise ATP via substrate-level phosphorylation. The Stickland reaction is the basic bioenergetic pathway of some bacteria of the genus Clostridium. Two other facts support Stickland fermentation in the RNA world. First, several Stickland amino acid pairs are synthesised in abiotic amino acid synthesis. This suggests that amino acids that could be used as an energy substrate were freely available. Second, anticodons that have complementary sequences often correspond to amino acids that form Stickland pairs. The main hypothesis of this paper is that pairs of complementary proto-adapters were assigned to Stickland amino acids pairs. There are signatures of this hypothesis in the genetic code. Furthermore, it is argued that the proto-adapters formed double strands that brought amino acid pairs into proximity to facilitate their mutual redox reaction, structurally constraining the anticodon pairs that are assigned to these amino acid pairs. Significance tests which randomise the code are performed to study the extent of the variability of the energetic (ATP) yield. Random assignments can lead to a substantial yield of ATP and maintain enough variability, thus selection can act and refine the assignments into a proto-code that optimises the energetic yield. Monte Carlo simulations are performed to evaluate the establishment of these simple proto-codes, based on amino acid substitutions and codon swapping. In all cases, donor amino acids are assigned to anticodons composed of U+G, and have low redundancy (1-2 codons), whereas acceptor amino acids are assigned to the the remaining codons. These bioenergetic and structural constraints allow for a metabolic role for amino acids before their co-option as catalyst cofactors.

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The Genetic Code and RNA-Amino Acid Affinities.

Publications

The Genetic Code and RNA-Amino Acid Affinities.

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