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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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Pairs of tRNAs with complementary anticodons bearing Stickland-reactive amino acid pairs. (Only the anticodon sequences shown). The three associations shown correspond to both anticodon complementarities, and Stickland electron donor/acceptor pairs of amino acids: (A) Glycine is an electron acceptor, whilst alanine is a donor. (B) Aspartic acid is an electron acceptor in the presence of valine and (C) also on the presence of alanine. (D) A different codon for glycine associates with one from serine (an electron donor). (A), (B) and (D) are legitimate pairs, in the sense that the anticodon bases match according to Watson-Crick pairing. (C) is an illegitimate association, since it involves the U-G pair. The lines represent the pair types: three for G-C pairs, two for A-U pairs and one for U-G pairs. Gly: glycine, Asp: aspartic acid Ala: alanine, Ser: serine.
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Figure 6: Pairs of tRNAs with complementary anticodons bearing Stickland-reactive amino acid pairs. (Only the anticodon sequences shown). The three associations shown correspond to both anticodon complementarities, and Stickland electron donor/acceptor pairs of amino acids: (A) Glycine is an electron acceptor, whilst alanine is a donor. (B) Aspartic acid is an electron acceptor in the presence of valine and (C) also on the presence of alanine. (D) A different codon for glycine associates with one from serine (an electron donor). (A), (B) and (D) are legitimate pairs, in the sense that the anticodon bases match according to Watson-Crick pairing. (C) is an illegitimate association, since it involves the U-G pair. The lines represent the pair types: three for G-C pairs, two for A-U pairs and one for U-G pairs. Gly: glycine, Asp: aspartic acid Ala: alanine, Ser: serine.

Mentions: The coevolution of the anticodon precursors as described above raises the following question: which amino acids were assigned to the new anticodons? To answer this question, we need to invoke a function for the proto-adapters. A catalytic role for the amino acids cannot be excluded, given that these are compounds with versatile chemical and structural properties. However, there is a gap between the stage when CCH were used as catalytic cofactors and the use of adaptors having a proto-code. What I propose is that the free anticodons were assigned to amino acids that complemented the Stickland role of the amino acids readily assigned to the complementary anticodons. This rule should apply for both legitimate and illegitimate complements (i.e., those involving G-U pairs). For example, in Figure 6 the anticodon GCC for glycine is complementary with the anticodon GGC for alanine. Glycine and alanine are Stickland pairs. Another pair would be formed between GUC (for aspartic acid) and GAC (for valine) where the amino acids are Stickland pairs. However, the illegitimate pair between GUC and GGC can also be formed. In fact, their amino acids, aspartic acid and alanine respectively, are also Stickland pairs. Table 1 lists the Stickland roles of some amino acids, including the ones appearing in the cycle (all of which are "Milller" amino acids, Figure 4). This observation leads to the following hypothesis:


Amino acid fermentation at the origin of the genetic code.

de Vladar HP - Biol. Direct (2012)

Pairs of tRNAs with complementary anticodons bearing Stickland-reactive amino acid pairs. (Only the anticodon sequences shown). The three associations shown correspond to both anticodon complementarities, and Stickland electron donor/acceptor pairs of amino acids: (A) Glycine is an electron acceptor, whilst alanine is a donor. (B) Aspartic acid is an electron acceptor in the presence of valine and (C) also on the presence of alanine. (D) A different codon for glycine associates with one from serine (an electron donor). (A), (B) and (D) are legitimate pairs, in the sense that the anticodon bases match according to Watson-Crick pairing. (C) is an illegitimate association, since it involves the U-G pair. The lines represent the pair types: three for G-C pairs, two for A-U pairs and one for U-G pairs. Gly: glycine, Asp: aspartic acid Ala: alanine, Ser: serine.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Pairs of tRNAs with complementary anticodons bearing Stickland-reactive amino acid pairs. (Only the anticodon sequences shown). The three associations shown correspond to both anticodon complementarities, and Stickland electron donor/acceptor pairs of amino acids: (A) Glycine is an electron acceptor, whilst alanine is a donor. (B) Aspartic acid is an electron acceptor in the presence of valine and (C) also on the presence of alanine. (D) A different codon for glycine associates with one from serine (an electron donor). (A), (B) and (D) are legitimate pairs, in the sense that the anticodon bases match according to Watson-Crick pairing. (C) is an illegitimate association, since it involves the U-G pair. The lines represent the pair types: three for G-C pairs, two for A-U pairs and one for U-G pairs. Gly: glycine, Asp: aspartic acid Ala: alanine, Ser: serine.
Mentions: The coevolution of the anticodon precursors as described above raises the following question: which amino acids were assigned to the new anticodons? To answer this question, we need to invoke a function for the proto-adapters. A catalytic role for the amino acids cannot be excluded, given that these are compounds with versatile chemical and structural properties. However, there is a gap between the stage when CCH were used as catalytic cofactors and the use of adaptors having a proto-code. What I propose is that the free anticodons were assigned to amino acids that complemented the Stickland role of the amino acids readily assigned to the complementary anticodons. This rule should apply for both legitimate and illegitimate complements (i.e., those involving G-U pairs). For example, in Figure 6 the anticodon GCC for glycine is complementary with the anticodon GGC for alanine. Glycine and alanine are Stickland pairs. Another pair would be formed between GUC (for aspartic acid) and GAC (for valine) where the amino acids are Stickland pairs. However, the illegitimate pair between GUC and GGC can also be formed. In fact, their amino acids, aspartic acid and alanine respectively, are also Stickland pairs. Table 1 lists the Stickland roles of some amino acids, including the ones appearing in the cycle (all of which are "Milller" amino acids, Figure 4). This observation leads to the following hypothesis:

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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