Amino acid fermentation at the origin of the genetic code.
Bottom Line: This redox reaction results in two keto acids that are employed to synthesise ATP via substrate-level phosphorylation.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.
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.
Mentions: The RNA world is an ancient evolutionary period characterised by a ribozyme-based metabolism. It is thought that the genetic code, or at least the precursors to the modern adapters (i.e. tRNAs, Figures 1 and 2), were established at that stage [, Ch. 5]. There are several theories that explain the current organisation of the code in terms of selective advantages, robustness against mutation, lateral gene transfer, biochemical and physical-chemical properties, and so forth. Most of these ideas build from the assumption that earlier, perhaps less accurate or complex codes existed, which evolved by selecting on different organisational principles, leading to the modern genetic code. Whilst most theories deal with the rearrangements to the code, only few directly address the question of how this code emerged. To some extent, the specific association between some amino acids and their codons can be explained by the formation of covalent complexes of dinucleotides and precursors to amino acids . Other ideas that have received more attention, are the stereochemical arguments (the structural affinity between amino acids and coding triplets) [3-6]. Furthermore, it has been proposed that the role of amino acids in an RNA world was to improve the catalytic activity of ribozymes , a function that requires coding, because ribozymes needed to bind the amino acid as cofactors in a specific way.