scholarly journals Error minimization and specificity could emerge in a genetic code as by-products of prebiotic evolution

2021 ◽  
Author(s):  
Evan Janzen ◽  
Yuning Shen ◽  
Ziwei Liu ◽  
Celia Blanco ◽  
Irene A. Chen
Keyword(s):  
Amino Acids ◽  
Genetic Code ◽  
Rna World ◽  
Emergent Property ◽  
Error Minimization ◽  
Standard Genetic Code ◽  
Major Transition ◽  
Selection For ◽  
Increased Activity ◽  
By Products

The emergence of the genetic code was a major transition in the evolution from a prebiotic RNA world to the earliest modern cells. A prominent feature of the standard genetic code is error minimization, or the tendency of mutations to be unusually conservative in preserving biophysical features of the amino acid. While error minimization is often assumed to result from natural selection, it has also been speculated that error minimization may be a by-product of emergence of the genetic code. During establishment of the genetic code in an RNA world, self-aminoacylating ribozymes would enforce the mapping of amino acids to anticodons. Here we show that expansion of the genetic code, through co-option of ribozymes for new substrates, could result in error minimization as an emergent property. Using self-aminoacylating ribozymes previously identified during an exhaustive search of sequence space, we measured the activity of thousands of candidate ribozymes on alternative substrates (activated analogs for tryptophan, phenylalanine, leucine, isoleucine, valine, and methionine). Related ribozymes exhibited preferences for biophysically similar substrates, indicating that co-option of existing ribozymes to adopt additional amino acids into the genetic code would itself lead to error minimization. Furthermore, ribozyme activity was positively correlated with specificity, indicating that selection for increased activity would also lead to increased specificity. These results demonstrate that by-products of the evolution and functional expansion of a ribozyme system could lead to adaptive properties of a genetic code. Such 'spandrels' could thus underlie significant prebiotic developments.

scholarly journals Some theoretical aspects of reprogramming the standard genetic code

2020 ◽  
Author(s):  
Kuba Nowak ◽  
Paweł Błażej ◽  
Małgorzata Wnetrzak ◽  
Dorota Mackiewicz ◽  
Paweł Mackiewicz
Keyword(s):  
Amino Acids ◽  
Genetic Code ◽  
Dna Sequences ◽  
Theoretical Perspective ◽  
Optimal Number ◽  
Optimal Size ◽  
Coding System ◽  
Standard Genetic Code ◽  
Nucleotide Mutation ◽  
Code Extension

1AbstractReprogramming of the standard genetic code in order to include non-canonical amino acids (ncAAs) opens a new perspective in medicine, industry and biotechnology. There are several methods of engineering the code, which allow us for storing new genetic information in DNA sequences and transmitting it into the protein world. Here, we investigate the problem of optimal genetic code extension from theoretical perspective. We assume that the new coding system should encode both canonical and new ncAAs using 64 classical codons. What is more, the extended genetic code should be robust to point nucleotide mutation and minimize the possibility of reversion from new to old information. In order to do so, we follow graph theory to study the properties of optimal codon sets, which can encode 20 canonical amino acids and stop coding signal. Finally, we describe the set of vacant codons that could be assigned to new amino acids. Moreover, we discuss the optimal number of the newly incorporated ncAAs and also the optimal size of codon blocks that are assigned to ncAAs.

scholarly journals Golden and Harmonic Mean in the Genetic Code

2017 ◽  
Author(s):  
Miloje M. Rakocevic
Keyword(s):  
Amino Acids ◽  
Genetic Code ◽  
Harmonic Mean ◽  
Standard Genetic Code ◽  
Code Table ◽  
Nucleotide Triplet

In previous two works [1], [2] we have shown the determination of genetic code by golden and harmonic mean within standard Genetic Code Table, i.e. nucleotide triplet table, whereas in this paper we show the same determination through a specific connection between two tables – of nucleotide doublets Table and triplets Table, over polarity of amino acids, measured by Cloister energy.

scholarly journals Did Amino Acid Side Chain Reactivity Dictate the Composition and Timing of Aminoacyl-tRNA Synthetase Evolution?

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 409
Author(s):  
Tamara L. Hendrickson ◽  
Whitney N. Wood ◽  
Udumbara M. Rathnayake
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Genetic Code ◽  
Chemical Reactivity ◽  
Trna Synthetase ◽  
Amino Acid Side Chain ◽  
Standard Genetic Code ◽  
Last Universal Common Ancestor ◽  
Trna Synthetases ◽  
Universal Common Ancestor

The twenty amino acids in the standard genetic code were fixed prior to the last universal common ancestor (LUCA). Factors that guided this selection included establishment of pathways for their metabolic synthesis and the concomitant fixation of substrate specificities in the emerging aminoacyl-tRNA synthetases (aaRSs). In this conceptual paper, we propose that the chemical reactivity of some amino acid side chains (e.g., lysine, cysteine, homocysteine, ornithine, homoserine, and selenocysteine) delayed or prohibited the emergence of the corresponding aaRSs and helped define the amino acids in the standard genetic code. We also consider the possibility that amino acid chemistry delayed the emergence of the glutaminyl- and asparaginyl-tRNA synthetases, neither of which are ubiquitous in extant organisms. We argue that fundamental chemical principles played critical roles in fixation of some aspects of the genetic code pre- and post-LUCA.

scholarly journals The Alanine World Model for the Development of the Amino Acid Repertoire in Protein Biosynthesis

2019 ◽  
Vol 20 (21) ◽  
pp. 5507 ◽  
Author(s):  
Vladimir Kubyshkin ◽  
Nediljko Budisa
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Genetic Code ◽  
Rna World ◽  
Protein Biosynthesis ◽  
Second Phase ◽  
Nucleotide Biosynthesis ◽  
The Core ◽  
Protein World ◽  
Α Helix

A central question in the evolution of the modern translation machinery is the origin and chemical ethology of the amino acids prescribed by the genetic code. The RNA World hypothesis postulates that templated protein synthesis has emerged in the transition from RNA to the Protein World. The sequence of these events and principles behind the acquisition of amino acids to this process remain elusive. Here we describe a model for this process by following the scheme previously proposed by Hartman and Smith, which suggests gradual expansion of the coding space as GC–GCA–GCAU genetic code. We point out a correlation of this scheme with the hierarchy of the protein folding. The model follows the sequence of steps in the process of the amino acid recruitment and fits well with the co-evolution and coenzyme handle theories. While the starting set (GC-phase) was responsible for the nucleotide biosynthesis processes, in the second phase alanine-based amino acids (GCA-phase) were recruited from the core metabolism, thereby providing a standard secondary structure, the α-helix. In the final phase (GCAU-phase), the amino acids were appended to the already existing architecture, enabling tertiary fold and membrane interactions. The whole scheme indicates strongly that the choice for the alanine core was done at the GCA-phase, while glycine and proline remained rudiments from the GC-phase. We suggest that the Protein World should rather be considered the Alanine World, as it predominantly relies on the alanine as the core chemical scaffold.

scholarly journals Golden and Harmonic Mean in the Genetic Code

2017 ◽  
Author(s):  
Miloje M. Rakocevic
Keyword(s):  
Amino Acids ◽  
Genetic Code ◽  
Harmonic Mean ◽  
Standard Genetic Code ◽  
International Conference ◽  
Theoretical Approaches ◽  
Code Table ◽  
Nucleotide Triplet ◽  
Polar Requirement

In previous two works (Rakočević, 1998; 2013), we have shown the determination of genetic code by golden and harmonic mean within standard Genetic Code Table, i.e. nucleotide triplet table, whereas in this paper we show the same determination through a specific connection between two tables – of nucleotide doublets Table and triplets Table, over polarity of amino acids, measured by Cloister energy in general, and by hydropathy and polar requirement, partialy. [This is the expanded version of the article published in Proceedings of the 2nd International Conference “Theoretical Approaches to BioInformation Systems” (TABIS.2013), September 17–22, 2013, Belgrade, Serbia. That first version is also stored, as Version 1, in OSF Preprints.]

scholarly journals The Origin of Prebiotic Information System in the Peptide/RNA World: A Simulation Model of the Evolution of Translation and the Genetic Code

Life ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 25 ◽  
Author(s):  
Sankar Chatterjee ◽  
Surya Yadav
Keyword(s):  
Amino Acids ◽  
Information System ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Genetic Code ◽  
Rna World ◽  
Trna Synthetase ◽  
Darwinian Evolution ◽  
Universal Genetic Code ◽  
Translation Machine

Information is the currency of life, but the origin of prebiotic information remains a mystery. We propose transitional pathways from the cosmic building blocks of life to the complex prebiotic organic chemistry that led to the origin of information systems. The prebiotic information system, specifically the genetic code, is segregated, linear, and digital, and it appeared before the emergence of DNA. In the peptide/RNA world, lipid membranes randomly encapsulated amino acids, RNA, and peptide molecules, which are drawn from the prebiotic soup, to initiate a molecular symbiosis inside the protocells. This endosymbiosis led to the hierarchical emergence of several requisite components of the translation machine: transfer RNAs (tRNAs), aminoacyl-tRNA synthetase (aaRS), messenger RNAs (mRNAs), ribosomes, and various enzymes. When assembled in the right order, the translation machine created proteins, a process that transferred information from mRNAs to assemble amino acids into polypeptide chains. This was the beginning of the prebiotic <i>information</i> age. The origin of the genetic code is enigmatic; herein, we propose an evolutionary explanation: the demand for a wide range of protein enzymes over peptides in the prebiotic reactions was the main selective pressure for the origin of information-directed protein synthesis. The molecular basis of the genetic code manifests itself in the interaction of aaRS and their cognate tRNAs. In the beginning, aminoacylated ribozymes used amino acids as a cofactor with the help of bridge peptides as a process for selection between amino acids and their cognate codons/anticodons. This process selects amino acids and RNA species for the next steps. The ribozymes would give rise to pre-tRNA and the bridge peptides to pre-aaRS. Later, variants would appear and evolution would produce different but specific aaRS-tRNA-amino acid combinations. Pre-tRNA designed and built pre-mRNA for the storage of information regarding its cognate amino acid. Each pre-mRNA strand became the storage device for the genetic information that encoded the amino acid sequences in triplet nucleotides. As information appeared in the digital languages of the codon within pre-mRNA and mRNA, and the genetic code for protein synthesis evolved, the prebiotic chemistry then became more organized and directional with the emergence of the translation and genetic code. The genetic code developed in three stages that are coincident with the refinement of the translation machines: the GNC code that was developed by the pre-tRNA/pre-aaRS /pre-mRNA machine, SNS code by the tRNA/aaRS/mRNA machine, and finally the universal genetic code by the tRNA/aaRS/mRNA/ribosome machine. We suggest the coevolution of translation machines and the genetic code. The emergence of the translation machines was the beginning of the Darwinian evolution, an interplay between information and its supporting structure. Our hypothesis provides the logical and incremental steps for the origin of the programmed protein synthesis. In order to better understand the prebiotic information system, we converted letter codons into numerical codons in the Universal Genetic Code Table. We have developed a software, called CATI (Codon-Amino Acid-Translator-Imitator), to translate randomly chosen numerical codons into corresponding amino acids and vice versa. This conversion has granted us insight into how the genetic code might have evolved in the peptide/RNA world. There is great potential in the application of numerical codons to bioinformatics, such as barcoding, DNA mining, or DNA fingerprinting. We constructed the likely biochemical pathways for the origin of translation and the genetic code using the Model-View-Controller (MVC) software framework, and the translation machinery step-by-step. While using AnyLogic software, we were able to simulate and visualize the entire evolution of the translation machines, amino acids, and the genetic code.

scholarly journals The Mutational Robustness of the Genetic Code and Codon Usage in Environmental Context: A Non-Extremophilic Preference?

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 773
Author(s):  
Ádám Radványi ◽  
Ádám Kun
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Physicochemical Properties ◽  
Genetic Code ◽  
Computational Models ◽  
Environmental Data ◽  
Standard Genetic Code ◽  
Mutational Robustness ◽  
Domains Of Life ◽  
History Of

The genetic code was evolved, to some extent, to minimize the effects of mutations. The effects of mutations depend on the amino acid repertoire, the structure of the genetic code and frequencies of amino acids in proteomes. The amino acid compositions of proteins and corresponding codon usages are still under selection, which allows us to ask what kind of environment the standard genetic code is adapted to. Using simple computational models and comprehensive datasets comprising genomic and environmental data from all three domains of Life, we estimate the expected severity of non-synonymous genomic mutations in proteins, measured by the change in amino acid physicochemical properties. We show that the fidelity in these physicochemical properties is expected to deteriorate with extremophilic codon usages, especially in thermophiles. These findings suggest that the genetic code performs better under non-extremophilic conditions, which not only explains the low substitution rates encountered in halophiles and thermophiles but the revealed relationship between the genetic code and habitat allows us to ponder on earlier phases in the history of Life.

scholarly journals Symmetrical Properties of Graph Representations of Genetic Codes: From Genotype to Phenotype

Symmetry ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 388 ◽  
Author(s):  
Marco José ◽  
Gabriel Zamudio
Keyword(s):  
Amino Acids ◽  
Genetic Code ◽  
Graph Representation ◽  
Symmetry Groups ◽  
Standard Genetic Code ◽  
Graph Representations ◽  
Symmetrical Structure ◽  
Genetic Codes ◽  
Mitochondrial Genetic Code

It has long been claimed that the mitochondrial genetic code possesses more symmetries than the Standard Genetic Code (SGC). To test this claim, the symmetrical structure of the SGC is compared with noncanonical genetic codes. We analyzed the symmetries of the graphs of codons and their respective phenotypic graph representation spanned by the RNY (R purines, Y pyrimidines, and N any of them) code, two RNA Extended codes, the SGC, as well as three different mitochondrial genetic codes from yeast, invertebrates, and vertebrates. The symmetry groups of the SGC and their corresponding phenotypic graphs of amino acids expose the evolvability of the SGC. Indeed, the analyzed mitochondrial genetic codes are more symmetrical than the SGC.

scholarly journals The Combinatorial Fusion Cascade to Generate the Standard Genetic Code

Life ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 975
Author(s):  
Alexander Nesterov-Mueller ◽  
Roman Popov
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Genetic Code ◽  
Temporal Order ◽  
Prebiotic Chemistry ◽  
Standard Genetic Code ◽  
The Road ◽  
Novel Technology ◽  
Three Stages ◽  
Combinatorial Fusion

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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