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Amino acid fermentation at the origin of the genetic code.

de Vladar HP - Biol. Direct (2012)

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.

View Article: PubMed Central - HTML - PubMed

Affiliation: hpvladar@ist.ac.at

ABSTRACT
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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Structural features of a double stranded RNA mini-helix of 11 nucleotides. Structural features of a double stranded RNA mini-helix of 11 nucleotides. The backbones of each chain are shown in blue and pink wire representations. Their anticodons are shown in tubes; showing also the bases. The putative attachment points of the amino acids are shown in red (at the third base of the anticodon position) and green (three bases before the anticodon). (A) Top view. (B) Side view. (C,D) Close-up showing the spatial proximity of the attachment nucleotides (shown in tube representation, colour code according to atoms), and its neighbours (wire representation). The putative atoms of attachment (2'COH) of the ribose, indicated by arrows, project outside the molecule. The molecule was modeled from a known crystal structure [69, PDB ID:353D].
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Figure 11: Structural features of a double stranded RNA mini-helix of 11 nucleotides. Structural features of a double stranded RNA mini-helix of 11 nucleotides. The backbones of each chain are shown in blue and pink wire representations. Their anticodons are shown in tubes; showing also the bases. The putative attachment points of the amino acids are shown in red (at the third base of the anticodon position) and green (three bases before the anticodon). (A) Top view. (B) Side view. (C,D) Close-up showing the spatial proximity of the attachment nucleotides (shown in tube representation, colour code according to atoms), and its neighbours (wire representation). The putative atoms of attachment (2'COH) of the ribose, indicated by arrows, project outside the molecule. The molecule was modeled from a known crystal structure [69, PDB ID:353D].

Mentions: Because of the symmetry of the double helix, the attachment point of the amino acids to their RNA chains needs to be at equivalent positions. At the same time the amino acids need to have spatial proximity. The anti-parallel nature of the double helix gives two alternatives that satisfy these two constraints, and are shown in Figure 11A,B. The first possibility is that amino acids are attached to the third base of the the anticodon (highlighted in red). The second possibility is that the amino acids are attached three bases before the first nucleotide of the anticodon (shown in green). These are the only two options in an 11 nucleotides mini-helix where the amino acids lie in the same physical plane.


Amino acid fermentation at the origin of the genetic code.

de Vladar HP - Biol. Direct (2012)

Structural features of a double stranded RNA mini-helix of 11 nucleotides. Structural features of a double stranded RNA mini-helix of 11 nucleotides. The backbones of each chain are shown in blue and pink wire representations. Their anticodons are shown in tubes; showing also the bases. The putative attachment points of the amino acids are shown in red (at the third base of the anticodon position) and green (three bases before the anticodon). (A) Top view. (B) Side view. (C,D) Close-up showing the spatial proximity of the attachment nucleotides (shown in tube representation, colour code according to atoms), and its neighbours (wire representation). The putative atoms of attachment (2'COH) of the ribose, indicated by arrows, project outside the molecule. The molecule was modeled from a known crystal structure [69, PDB ID:353D].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376031&req=5

Figure 11: Structural features of a double stranded RNA mini-helix of 11 nucleotides. Structural features of a double stranded RNA mini-helix of 11 nucleotides. The backbones of each chain are shown in blue and pink wire representations. Their anticodons are shown in tubes; showing also the bases. The putative attachment points of the amino acids are shown in red (at the third base of the anticodon position) and green (three bases before the anticodon). (A) Top view. (B) Side view. (C,D) Close-up showing the spatial proximity of the attachment nucleotides (shown in tube representation, colour code according to atoms), and its neighbours (wire representation). The putative atoms of attachment (2'COH) of the ribose, indicated by arrows, project outside the molecule. The molecule was modeled from a known crystal structure [69, PDB ID:353D].
Mentions: Because of the symmetry of the double helix, the attachment point of the amino acids to their RNA chains needs to be at equivalent positions. At the same time the amino acids need to have spatial proximity. The anti-parallel nature of the double helix gives two alternatives that satisfy these two constraints, and are shown in Figure 11A,B. The first possibility is that amino acids are attached to the third base of the the anticodon (highlighted in red). The second possibility is that the amino acids are attached three bases before the first nucleotide of the anticodon (shown in green). These are the only two options in an 11 nucleotides mini-helix where the amino acids lie in the same physical plane.

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.

View Article: PubMed Central - HTML - PubMed

Affiliation: hpvladar@ist.ac.at

ABSTRACT
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.

Show MeSH