scholarly journals Formation of the Codon Degeneracy during Interdependent Development between Metabolism and Replication

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 2023
Author(s):  
Dirson Jian Li
Keyword(s):  
Amino Acids ◽  
Genetic Code ◽  
Driving Force ◽  
Sequence Evolution ◽  
Base Pairs ◽  
Random Sequences ◽  
Relative Stabilities ◽  
Base Substitutions ◽  
Codon Degeneracy

Nirenberg’s genetic code chart shows a profound correspondence between codons and amino acids. The aim of this article is to try to explain the primordial formation of the codon degeneracy. It remains a puzzle how informative molecules arose from the supposed prebiotic random sequences. If introducing an initial driving force based on the relative stabilities of triplex base pairs, the prebiotic sequence evolution became innately nonrandom. Thus, the primordial assignment of the 64 codons to the 20 amino acids has been explained in detail according to base substitutions during the coevolution of tRNAs with aaRSs; meanwhile, the classification of aaRSs has also been explained.

scholarly journals Basic principles of the genetic code extension

2019 ◽  
Author(s):  
Paweł Błażej ◽  
Małgorzata Wnetrzak ◽  
Dorota Mackiewicz ◽  
Paweł Mackiewicz
Keyword(s):  
Amino Acids ◽  
Genetic Code ◽  
Point Mutations ◽  
Coding System ◽  
Base Pairs ◽  
Induced Subgraphs ◽  
Single Nucleotide ◽  
Basic Principles ◽  
Code Extension ◽  
Incremental Addition

AbstractCompounds including non-canonical amino acids or other artificially designed molecules can find a lot of applications in medicine, industry and biotechnology. They can be produced thanks to the modification or extension of the standard genetic code (SGC). Such peptides or proteins including the non-canonical amino acids can be constantly delivered in a stable way by organisms with the customized genetic code. Among several methods of engineering the code, using non-canonical base pairs is especially promising, because it enables generating many new codons, which can be used to encode any new amino acid. Since even one pair of new bases can extend the SGC up to 216 codons generated by six-letter nucleotide alphabet, the extension of the SGC can be achieved in many ways. Here, we proposed a stepwise procedure of the SGC extension with one pair of non-canonical bases to minimize the consequences of point mutations. We reported relationships between codons in the framework of graph theory. All 216 codons were represented as nodes of the graph, whereas its edges were induced by all possible single nucleotide mutations occurring between codons. Therefore, every set of canonical and newly added codons induces a specific subgraph. We characterized the properties of the induced subgraphs generated by selected sets of codons. Thanks to that, we were able to describe a procedure for incremental addition of the set of meaningful codons up to the full coding system consisting of three pairs of bases. The procedure of gradual extension of the SGC makes the whole system robust to changing genetic information due to mutations and is compatible with the views assuming that codons and amino acids were added successively to the primordial SGC, which evolved to minimize harmful consequences of mutations or mistranslations of encoded proteins.

scholarly journals Constrained mutational sampling of amino acids in HIV-1 protease evolution

2018 ◽  
Author(s):  
Jeffrey I. Boucher ◽  
Troy W. Whitfield ◽  
Ann Dauphin ◽  
Gily Nachum ◽  
Carl Hollins ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Genetic Code ◽  
Protein Sequence ◽  
Fitness Landscape ◽  
Sequence Evolution ◽  
Single Mutation ◽  
The Impact ◽  
Protein Sequence Evolution ◽  
Hiv 1

AbstractThe evolution of HIV-1 protein sequences should be governed by a combination of factors including nucleotide mutational probabilities, the genetic code, and fitness. The impact of these factors on protein sequence evolution are interdependent, making it challenging to infer the individual contribution of each factor from phylogenetic analyses alone. We investigated the protein sequence evolution of HIV-1 by determining an experimental fitness landscape of all individual amino acid changes in protease. We compared our experimental results to the frequency of protease variants in a publicly available dataset of 32,163 sequenced isolates from drug-naïve individuals. The most common amino acids in sequenced isolates supported robust experimental fitness, indicating that the experimental fitness landscape captured key features of selection acting on protease during viral infections of hosts. Amino acid changes requiring multiple mutations from the likely ancestor were slightly less likely to support robust experimental fitness than single mutations, consistent with the genetic code favoring chemically conservative amino acid changes. Amino acids that were common in sequenced isolates were predominantly accessible by single mutations from the likely protease ancestor. Multiple mutations commonly observed in isolates were accessible by mutational walks with highly fit single mutation intermediates. Our results indicate that the prevalence of multiple base mutations in HIV-1 protease is strongly influenced by mutational sampling.

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.]

scholarly journals Basic principles of the genetic code extension

2020 ◽  
Vol 7 (2) ◽  
pp. 191384
Author(s):  
Paweł Błażej ◽  
Małgorzata Wnetrzak ◽  
Dorota Mackiewicz ◽  
Paweł Mackiewicz
Keyword(s):  
Amino Acids ◽  
Genetic Code ◽  
Point Mutations ◽  
Coding System ◽  
Base Pairs ◽  
Induced Subgraphs ◽  
Single Nucleotide ◽  
Basic Principles ◽  
Code Extension ◽  
Incremental Addition

Compounds including non-canonical amino acids (ncAAs) or other artificially designed molecules can find a lot of applications in medicine, industry and biotechnology. They can be produced thanks to the modification or extension of the standard genetic code (SGC). Such peptides or proteins including the ncAAs can be constantly delivered in a stable way by organisms with the customized genetic code. Among several methods of engineering the code, using non-canonical base pairs is especially promising, because it enables generating many new codons, which can be used to encode any new amino acid. Since even one pair of new bases can extend the SGC up to 216 codons generated by a six-letter nucleotide alphabet, the extension of the SGC can be achieved in many ways. Here, we proposed a stepwise procedure of the SGC extension with one pair of non-canonical bases to minimize the consequences of point mutations. We reported relationships between codons in the framework of graph theory. All 216 codons were represented as nodes of the graph, whereas its edges were induced by all possible single nucleotide mutations occurring between codons. Therefore, every set of canonical and newly added codons induces a specific subgraph. We characterized the properties of the induced subgraphs generated by selected sets of codons. Thanks to that, we were able to describe a procedure for incremental addition of the set of meaningful codons up to the full coding system consisting of three pairs of bases. The procedure of gradual extension of the SGC makes the whole system robust to changing genetic information due to mutations and is compatible with the views assuming that codons and amino acids were added successively to the primordial SGC, which evolved minimizing harmful consequences of mutations or mistranslations of encoded proteins.

scholarly journals Genetic code: Chemical Distinctions of Protein Amino Acids

2017 ◽  
Author(s):  
Miloje M. Rakočević
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 "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.

scholarly journals Lambda repressor recognizes the approximately 2-fold symmetric half-operator sequences asymmetrically

1989 ◽  
Vol 86 (17) ◽  
pp. 6513-6517 ◽  
Author(s):  
A Sarai ◽  
Y Takeda
Keyword(s):  
Amino Acids ◽  
Symmetric Operator ◽  
Dna Bases ◽  
Base Substitution ◽  
Base Pairs ◽  
Lambda Repressor ◽  
Base Substitutions ◽  
Protein Dna Interactions ◽  
Operator Sequence ◽  
Recognition Code

Results of systematic base-substitution experiments suggest that the lambda repressor dimer, made of identical subunits, recognizes the "pseudo(2-fold)symmetric" operator sequence asymmetrically. Base substitutions within the consensus half of the operator affect binding more than base substitutions within the nonconsensus half of the operator. Furthermore, changing the nonconsensus base pairs to the consensus base pairs does not increase, but decreases, binding. Evidently, the two subunits of the lambda repressor dimer bind to the two halves of the operator differently. This is consistent with the recently determined crystal structure of the complex, which shows that the relative positioning of the amino acids to the DNA bases are slightly different in the two halves of the operator. The sequence-specific interactions indicated by the systematic base-substitution experiments correlate well with the locations of the specific contacts found in the complex. Thus, the amino acids of lambda repressor, mainly of alpha 3-helix and the N-terminus arm, seem to directly read-out the DNA sequence by forming specific hydrogen bonds and hydrophobic contacts to the DNA bases. The observed asymmetric recognition suggests that no recognition code governs amino acids and DNA bases in protein-DNA interactions.

scholarly journals Constrained Mutational Sampling of Amino Acids in HIV-1 Protease Evolution

2019 ◽  
Vol 36 (4) ◽  
pp. 798-810 ◽  
Author(s):  
Jeffrey I Boucher ◽  
Troy W Whitfield ◽  
Ann Dauphin ◽  
Gily Nachum ◽  
Carl Hollins ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Genetic Code ◽  
Protein Sequence ◽  
Fitness Landscape ◽  
Sequence Evolution ◽  
Single Mutation ◽  
The Impact ◽  
Protein Sequence Evolution ◽  
Hiv 1

Abstract The evolution of HIV-1 protein sequences should be governed by a combination of factors including nucleotide mutational probabilities, the genetic code, and fitness. The impact of these factors on protein sequence evolution is interdependent, making it challenging to infer the individual contribution of each factor from phylogenetic analyses alone. We investigated the protein sequence evolution of HIV-1 by determining an experimental fitness landscape of all individual amino acid changes in protease. We compared our experimental results to the frequency of protease variants in a publicly available data set of 32,163 sequenced isolates from drug-naïve individuals. The most common amino acids in sequenced isolates supported robust experimental fitness, indicating that the experimental fitness landscape captured key features of selection acting on protease during viral infections of hosts. Amino acid changes requiring multiple mutations from the likely ancestor were slightly less likely to support robust experimental fitness than single mutations, consistent with the genetic code favoring chemically conservative amino acid changes. Amino acids that were common in sequenced isolates were predominantly accessible by single mutations from the likely protease ancestor. Multiple mutations commonly observed in isolates were accessible by mutational walks with highly fit single mutation intermediates. Our results indicate that the prevalence of multiple-base mutations in HIV-1 protease is strongly influenced by mutational sampling.

scholarly journals Transferability of N-terminal mutations of pyrrolysyl-tRNA synthetase in one species to that in another species on unnatural amino acid incorporation efficiency

Amino Acids ◽  
2020 ◽  
Author(s):  
Thomas L. Williams ◽  
Debra J. Iskandar ◽  
Alexander R. Nödling ◽  
Yurong Tan ◽  
Louis Y. P. Luk ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Genetic Code ◽  
Unnatural Amino Acids ◽  
Trna Synthetase ◽  
Unnatural Amino Acid ◽  
Amino Acid Incorporation ◽  
Acid Incorporation ◽  
Genetic Code Expansion ◽  
Incorporation Efficiency

AbstractGenetic code expansion is a powerful technique for site-specific incorporation of an unnatural amino acid into a protein of interest. This technique relies on an orthogonal aminoacyl-tRNA synthetase/tRNA pair and has enabled incorporation of over 100 different unnatural amino acids into ribosomally synthesized proteins in cells. Pyrrolysyl-tRNA synthetase (PylRS) and its cognate tRNA from Methanosarcina species are arguably the most widely used orthogonal pair. Here, we investigated whether beneficial effect in unnatural amino acid incorporation caused by N-terminal mutations in PylRS of one species is transferable to PylRS of another species. It was shown that conserved mutations on the N-terminal domain of MmPylRS improved the unnatural amino acid incorporation efficiency up to five folds. As MbPylRS shares high sequence identity to MmPylRS, and the two homologs are often used interchangeably, we examined incorporation of five unnatural amino acids by four MbPylRS variants at two temperatures. Our results indicate that the beneficial N-terminal mutations in MmPylRS did not improve unnatural amino acid incorporation efficiency by MbPylRS. Knowledge from this work contributes to our understanding of PylRS homologs which are needed to improve the technique of genetic code expansion in the future.

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