Combinatorial Fusion Rules to Describe Codon Assignment in the Standard Genetic Code

Nesterov‐Mueller, Alexander; Popov, Roman S.; Seligmann, Hervé

doi:10.3390/life11010004

Cited by 3 publications

(4 citation statements)

References 91 publications

(49 reference statements)

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“…Any amino acid, even a noncanonical one, could take part in the beginning of coded peptide synthesis. The same point of view is substantiated by Nesterov-Mueller et al [89] in a recent original, yet too speculative hypothesis of "fusion of four independently coexisting protocodes." Even the authors admit that it is not clear how these protocodes could have arisen.…”

Section: Transition From Noncoded To Codedsupporting

confidence: 55%

On the Origin of Genetically Coded Protein Synthesis

Kovalenko¹

2021

Russ J Bioorg Chem

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How proteins with a specific amino acid sequence are synthesized in living organisms is no longer a mystery after the deciphering of the genetic code six decades ago. However, the origin of the system of genetically coded protein synthesis is still the subject of hypotheses that are only partially experimentally justified. Based on the review of works mainly of the last decade, the author formulated a hypothesis that largely concretizes certain stages of the formation of the translation system and the genetic code. The hypothesis is based on the concept of evolutionary reduction of the ambiguity of the primordial code. The distinctive positions of the hypothesis are as follows: (i) the emergence of aptamers, enriching the protocell by the rare catalytically active amino acids, and their evolutionary transformation into aaRS-like ribozymes which resulted in the operational code, (ii) simultaneous participation of a large number of amino acids (including noncanonical) in the formation of operational and genetic codes, (iii) the recognition of the whole codon of mRNA by the anticodon loop of proto-tRNA from the very beginning of coded protein synthesis, (iv) the coevolution of the operational and genetic codes that eliminated their initial ambiguity.

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Section: Transition From Noncoded To Codedsupporting

confidence: 55%

On the Origin of Genetically Coded Protein Synthesis

Kovalenko¹

2021

Russ J Bioorg Chem

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“…The combinatorial fusion of AU- and GC-protocodes proposed by Nesterov-Mueller and Popov absorbed these ideas of the competing entities and the separated AU and GC early phases [ 34 ]. It described with surprising simplicity the codon assignments in the SGC, including the codons for the non-canonical amino acids, the appearance of stop codons, as well some deviations from the SGC in mitochondria [ 35 ].…”

Section: Methodsmentioning

confidence: 99%

Screening for Primordial RNA–Peptide Interactions Using High-Density Peptide Arrays

Jenne

Berezkin

Tempel

et al. 2023

Life

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RNA–peptide interactions are an important factor in the origin of the modern mechanism of translation and the genetic code. Despite great progress in the bioinformatics of RNA–peptide interactions due to the rapid growth in the number of known RNA–protein complexes, there is no comprehensive experimental method to take into account the influence of individual amino acids on non-covalent RNA–peptide bonds. First, we designed the combinatorial libraries of primordial peptides according to the combinatorial fusion rules based on Watson–Crick mutations. Next, we used high-density peptide arrays to investigate the interaction of primordial peptides with their cognate homo-oligonucleotides. We calculated the interaction scores of individual peptide fragments and evaluated the influence of the peptide length and its composition on the strength of RNA binding. The analysis shows that the amino acids phenylalanine, tyrosine, and proline contribute significantly to the strong binding between peptides and homo-oligonucleotides, while the sum charge of the peptide does not have a significant effect. We discuss the physicochemical implications of the combinatorial fusion cascade, a hypothesis that follows from the amino acid partition used in the work.

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“…The fusion rules for the recessive protocodes are based on the same mutations, but in the 1st position or in positions 1 and 3. Having identified this fact from the fusion cascade, Nesterov-Mueller et al suggested that such combinations could be induced within the framework of the kissing hairpin geometry by means of complementary codons [ 32 ]. Attempts to explain the emergence of the genetic code from complementary tRNA hairpins were also undertaken by Rodin and Ohno [ 35 ].…”

Section: Combinatorial Fusion Cascade and Its Formalismmentioning

confidence: 99%

“…The recent discovery of the fusion rules integrated into the SGC led to a simple and mathematically exact description of the codon distribution over canonical amino acids [ 31 , 32 ]. According to these rules, the modern genetic code arose from the fusion of dominant and recessive protocodes, which initially competed for the same triplets.…”

Section: Introductionmentioning

confidence: 99%

The Combinatorial Fusion Cascade to Generate the Standard Genetic Code

Nesterov‐Mueller

Popov

2021

Life

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Combinatorial fusion cascade was proposed as a transition stage between prebiotic chemistry and early forms of life. The combinatorial fusion cascade consists of three stages: eight initial complimentary pairs of amino acids, four protocodes, and the standard genetic code. The initial complimentary pairs and the protocodes are divided into dominant and recessive entities. The transitions between these stages obey the same combinatorial fusion rules for all amino acids. The combinatorial fusion cascade mathematically describes the codon assignments in the standard genetic code. It explains the availability of amino acids with the even and odd numbers of codons, the appearance of stop codons, inclusion of novel canonical amino acids, exceptional high numbers of codons for amino acids arginine, leucine, and serine, and the temporal order of amino acid inclusion into the genetic code. The temporal order of amino acids within the cascade is congruent with the consensus temporal order previously derived from the similarities between the available hypotheses. The control over the combinatorial fusion cascades would open the road for a novel technology to develop artificial microorganisms.

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Combinatorial Fusion Rules to Describe Codon Assignment in the Standard Genetic Code

Cited by 3 publications

References 91 publications

On the Origin of Genetically Coded Protein Synthesis

On the Origin of Genetically Coded Protein Synthesis

Screening for Primordial RNA–Peptide Interactions Using High-Density Peptide Arrays

The Combinatorial Fusion Cascade to Generate the Standard Genetic Code

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