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

We propose combinatorial fusion rules that describe the codon assignment in the standard genetic code simply and uniformly for all canonical amino acids. These rules become obvious if the origin of the standard genetic code is considered as a result of a fusion of four protocodes: Two dominant AU and GC protocodes and two recessive AU and GC protocodes. The biochemical meaning of the fusion rules consists of retaining the complementarity between cognate codons of the small hydrophobic amino acids and large charged or polar amino acids within the protocodes. The proto tRNAs were assembled in form of two kissing hairpins with 9-base and 10-base loops in the case of dominant protocodes and two 9-base loops in the case of recessive protocodes. The fusion rules reveal the connection between the stop codons, the non-canonical amino acids, pyrrolysine and selenocysteine, and deviations in the translation of mitochondria. Using fusion rules, we predicted the existence of additional amino acids that are essential for the development of the standard genetic code. The validity of the proposed partition of the genetic code into dominant and recessive protocodes is considered referring to state-of-the-art hypotheses. The formation of two aminoacyl-tRNA synthetase classes is compatible with four-protocode partition.

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

Genes ◽

10.3390/genes12030409 ◽

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.

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The Combinatorial Fusion Cascade to Generate the Standard Genetic Code

Life ◽

10.3390/life11090975 ◽

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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Evolution of Life on Earth: tRNA, Aminoacyl-tRNA Synthetases and the Genetic Code

Life ◽

10.3390/life10030021 ◽

2020 ◽

Vol 10 (3) ◽

pp. 21 ◽

Cited By ~ 6

Author(s):

Lei Lei ◽

Zachary F Burton

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Genetic Code ◽

Elongation Factor ◽

Trna Synthetase ◽

Aminoacyl Trna Synthetase ◽

Trna Synthetases ◽

Amino Acid Code ◽

Evolution Of Life ◽

Life On Earth

Life on Earth and the genetic code evolved around tRNA and the tRNA anticodon. We posit that the genetic code initially evolved to synthesize polyglycine as a cross-linking agent to stabilize protocells. We posit that the initial amino acids to enter the code occupied larger sectors of the code that were then invaded by incoming amino acids. Displacements of amino acids follow selection rules. The code sectored from a glycine code to a four amino acid code to an eight amino acid code to an ~16 amino acid code to the standard 20 amino acid code with stops. The proposed patterns of code sectoring are now most apparent from patterns of aminoacyl-tRNA synthetase evolution. The Elongation Factor-Tu GTPase anticodon-codon latch that checks the accuracy of translation appears to have evolved at about the eight amino acid to ~16 amino acid stage. Before evolution of the EF-Tu latch, we posit that both the 1st and 3rd anticodon positions were wobble positions. The genetic code evolved via tRNA charging errors and via enzymatic modifications of amino acids joined to tRNAs, followed by tRNA and aminoacyl-tRNA synthetase differentiation. Fidelity mechanisms froze the code by inhibiting further innovation.

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Alternative genetic code for amino acids and transfer RNA revisited

BioMolecular Concepts ◽

10.1515/bmc-2013-0002 ◽

2013 ◽

Vol 4 (3) ◽

pp. 309-318 ◽

Cited By ~ 6

Author(s):

Kiyofumi Hamashima ◽

Akio Kanai

Keyword(s):

Genetic Code ◽

Translational Control ◽

Trna Synthetase ◽

Evolutionary Divergence ◽

Aminoacyl Trna Synthetase ◽

Standard Genetic Code ◽

Standard Code ◽

Rna Biosynthesis ◽

Nematode Worm ◽

Eukaryotic Genomes

AbstractThe genetic code is highly conserved among all organisms and its evolution is thought to be strictly limited. However, an increasing number of studies have reported non-standard codes in prokaryotic and eukaryotic genomes. Most of these deviations from the standard code are attributable to tRNA changes relating to, for example, codon/anticodon base pairing and tRNA/aminoacyl-tRNA synthetase recognition. In this review, we focus on tRNA, a key molecule in the translation of the genetic code, and summarize the most recently published information on the evolutionary divergence of the tRNAs. Surprisingly, although higher eukaryotes, such as the nematode (worm), utilize the standard genetic code, newly identified nematode-specific tRNAs (nev-tRNAs) translate nucleotides in a manner that transgresses the code. Furthermore, a variety of additional functions of tRNAs, beyond their translation of the genetic code, have emerged rapidly. We also review these intriguing new aspects of tRNA, which have potential impacts on translational control, RNA silencing, antibiotic resistance, RNA biosynthesis, and transcriptional regulation.

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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 ◽

10.1007/s00726-020-02927-z ◽

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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Some theoretical aspects of reprogramming the standard genetic code

10.1101/2020.09.12.294553 ◽

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.

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