scholarly journals On the Importance of Asymmetry in the Phenotypic Expression of the Genetic Code upon the Molecular Evolution of Proteins

Symmetry ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 997
Author(s):  
Marco V. José ◽  
Gabriel S. Zamudio
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Genetic Code ◽  
Phenotypic Expression ◽  
Standard Genetic Code ◽  
Specific Amino Acid ◽  
Trna Synthetases ◽  
Probability Of Occurrence ◽  
Genetic Codes ◽  
Evolution Of Proteins

The standard genetic code (SGC) is a mapping between the 64 possible arrangements of the four RNA nucleotides (C, A, U, G) into triplets or codons, where 61 codons are assigned to a specific amino acid and the other three are stop codons for terminating protein synthesis. Aminoacyl-tRNA synthetases (aaRSs) are responsible for implementing the SGC by specifically amino-acylating only its cognate transfer RNA (tRNA), thereby linking an amino acid with its corresponding anticodon triplets. tRNAs molecules bind each codon with its anticodon. To understand the meaning of symmetrical/asymmetrical properties of the SGC, we designed synthetic genetic codes with known symmetries and with the same degeneracy of the SGC. We determined their impact on the substitution rates for each amino acid under a neutral model of protein evolution. We prove that the phenotypic graphs of the SGC for codons and anticodons for all the possible arrangements of nucleotides are asymmetric and the amino acids do not form orbits. In the symmetrical synthetic codes, the amino acids are grouped according to their codonicity, this is the number of triplets encoding a given amino acid. Both the SGC and symmetrical synthetic codes exhibit a probability of occurrence of the amino acids proportional to their degeneracy. Unlike the SGC, the synthetic codes display a constant probability of occurrence of the amino acid according to their codonicity. The asymmetry of the phenotypic graphs of codons and anticodons of the SGC, has important implications on the evolutionary processes of proteins.

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 Optimization of Expanded Genetic Codes via Genetic Algorithms

2018 ◽  
Author(s):  
Maísa de Carvalho Silva ◽  
Lariza Laura De Oliveira ◽  
Renato Tinós
Keyword(s):  
Amino Acids ◽  
Genetic Algorithms ◽  
Amino Acid ◽  
Genetic Code ◽  
Unnatural Amino Acids ◽  
Genetically Modified Organisms ◽  
Fitness Function ◽  
Unnatural Amino Acid ◽  
Standard Genetic Code ◽  
Genetic Codes

In the last decades, researchers have proposed the use of genetically modified organisms that utilize unnatural amino acids, i.e., amino acids other than the 20 amino acids encoded in the standard genetic code. Unnatural amino acids have been incorporated into genetically engineered organisms for the development of new drugs, fuels and chemicals. When new amino acids are incorporated, it is necessary to modify the standard genetic code. Expanded genetic codes have been created without considering the robustness of the code. The objective of this work is the use of genetic algorithms (GAs) for the optimization of expanded genetic codes. The GA indicates which codons of the standard genetic code should be used to encode a new unnatural amino acid. The fitness function has two terms; one for robustness of the new code and another that takes into account the frequency of use of amino acids. Experiments show that, by controlling the weighting between the two terms, it is possible to obtain more or less amino acid substitutions at the same time that the robustness is minimized.

scholarly journals Universal Codons with Enrichment from GC to AU Nucleotide Composition Reveal a Chronological Assignment from Early to Late Along with LUCA Formation

Life ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 81 ◽  
Author(s):  
Anastas Gospodinov ◽  
Dimiter Kunnev
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Genetic Code ◽  
Driving Forces ◽  
Active Role ◽  
Nucleotide Composition ◽  
Zonal Distribution ◽  
Trna Synthetases ◽  
Universal Common Ancestor ◽  
Complete Set

The emergence of a primitive genetic code should be considered the most essential event during the origin of life. Almost a complete set of codons (as we know them) should have been established relatively early during the evolution of the last universal common ancestor (LUCA) from which all known organisms descended. Many hypotheses have been proposed to explain the driving forces and chronology of the evolution of the genetic code; however, none is commonly accepted. In the current paper, we explore the features of the genetic code that, in our view, reflect the mechanism and the chronological order of the origin of the genetic code. Our hypothesis postulates that the primordial RNA was mostly GC-rich, and this bias was reflected in the order of amino acid codon assignment. If we arrange the codons and their corresponding amino acids from GC-rich to AU-rich, we find that: 1. The amino acids encoded by GC-rich codons (Ala, Gly, Arg, and Pro) are those that contribute the most to the interactions with RNA (if incorporated into short peptides). 2. This order correlates with the addition of novel functions necessary for the evolution from simple to longer folded peptides. 3. The overlay of aminoacyl-tRNA synthetases (aaRS) to the amino acid order produces a distinctive zonal distribution for class I and class II suggesting an interdependent origin. These correlations could be explained by the active role of the bridge peptide (BP), which we proposed earlier in the evolution of the genetic code.

scholarly journals Oxidation of cellular amino acid pools leads to cytotoxic mistranslation of the genetic code

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Tammy J Bullwinkle ◽  
Noah M Reynolds ◽  
Medha Raina ◽  
Adil Moghal ◽  
Eleftheria Matsa ◽  
...  
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Genetic Code ◽  
Trna Synthetase ◽  
Control Mechanisms ◽  
Cellular Toxicity ◽  
Trna Synthetases ◽  
Aminoacyl Trna Synthetases ◽  
The Cost

Aminoacyl-tRNA synthetases use a variety of mechanisms to ensure fidelity of the genetic code and ultimately select the correct amino acids to be used in protein synthesis. The physiological necessity of these quality control mechanisms in different environments remains unclear, as the cost vs benefit of accurate protein synthesis is difficult to predict. We show that in Escherichia coli, a non-coded amino acid produced through oxidative damage is a significant threat to the accuracy of protein synthesis and must be cleared by phenylalanine-tRNA synthetase in order to prevent cellular toxicity caused by mis-synthesized proteins. These findings demonstrate how stress can lead to the accumulation of non-canonical amino acids that must be excluded from the proteome in order to maintain cellular viability.

Many alternative and theoretical genetic codes are more robust to amino acid replacements than the standard genetic code

2019 ◽  
Vol 464 ◽  
pp. 21-32 ◽  
Author(s):  
Paweł Błażej ◽  
Małgorzata Wnętrzak ◽  
Dorota Mackiewicz ◽  
Przemysław Gagat ◽  
Paweł Mackiewicz
Keyword(s):  
Amino Acid ◽  
Genetic Code ◽  
Standard Genetic Code ◽  
Genetic Codes

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.

scholarly journals Packing the Standard Genetic Code in its box: 3-dimensional late Crick wobble

2021 ◽  
Author(s):  
Michael Yarus
Keyword(s):  
Amino Acid ◽  
Genetic Code ◽  
Dimensional Space ◽  
Parallel Evolution ◽  
Three Dimensional ◽  
Standard Genetic Code ◽  
3 Dimensional ◽  
Combinatorial Properties ◽  
Genetic Codes ◽  
Level Order

AbstractMinimally-evolved codes are constructed with randomly chosen Standard Genetic Code (SGC) triplets, and completed with completely random triplet assignments. Such “genetic codes” have not evolved, but retain SGC qualities. Retained qualities are inescapable, part of the logic of code evolution. For example, sensitivity of coding to arbitrary assignments, which must be <≈ 10%, is intrinsic. Such sensitivity comes from elementary combinatorial properties of coding, and constrains any SGC evolution hypothesis. Similarly, evolution of last-evolved functions is difficult, due to late kinetic phenomena, likely common across codes. Census of minimally-evolved code assignments shows that shape and size of wobble domains controls packing into a coding table, shifting the accuracy of codon assignments. Access to the SGC therefore requires a plausible pathway to limited randomness, avoiding difficult completion while packing a highly ordered, degenerate code into a fixed three-dimensional space. Late Crick wobble in a 3-dimensional genetic code previously assembled by lateral transfer satisfies these varied, simultaneous requirements. By allowing parallel evolution of SGC domains, it can yield shortened evolution to SGC-level order, and allow the code to arise in smaller populations. It effectively yields full codes. Less obviously, it unifies well-studied sources for order in amino acid coding, including a minority of stereochemical triplet-amino acid associations. Finally, fusion of its intermediates into the definitive SGC is credible, mirroring broadly-accepted later events in cellular evolution.

scholarly journals Genetic code: Chemical Distinctions of Protein Amino Acids

2017 ◽  
Author(s):  
Miloje M. Rakocevic
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Genetic Code ◽  
Standard Genetic Code ◽  
Atom Number ◽  
Canonical Bases ◽  
Ordinal Numbers ◽  
Intelligent Structures ◽  
Protein Amino Acids

In the work it is shown that 20 protein amino acids ("the canonical amino acids" within the genetic code) appear to be a whole and very symmetrical system, in many ways, all based on strict chemical distinctions from the aspect of their similarity, complexity, stereochemical and diversity types. By this, all distinctions are accompanied by specific arithmetical and algebraic regularities, including the existence of amino acid ordinal numbers from 1 to 20. The classification of amino acids into two decades (1-10 and 11-20) appears to be in a strict correspondence with the atom number balances. From the presented "ideal" and "intelligent" structures and arrangements follow the conclusions that the genetic code was complete even in prebiotic conditions (as a set of 20 canonical amino acids and the set of 2+2 pyrimidine / purine canonical bases, respectively); and the notion "evolution" of the genetic code can only mean the degree of freedom of standard genetic code, i.e. the possible exceptions and deviations from the standard genetic code. [This is the second version with minimal interventions in the text. In addition, one passage was added in front of the second star, with quoting of T. Jukes. Added is Remark 4 and a more adequate shading in the Table inside Box 2.]

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