The Origin and Evolution of the Genetic Code: 100th Anniversary Year of the Birth of Francis Crick

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Genetics and Genomics".

Deadline for manuscript submissions: closed (15 January 2017) | Viewed by 94915

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor


E-Mail Website
Guest Editor
Department of Biological Science and Technology, Tokyo University of Science, 6-3-1 Niijuku, Katsushika-ku, Tokyo 125-8585, Japan
Interests: origin of life; origin of the genetic code; origin of biological homochirality

Special Issue Information

Dear Colleagues,

The genetic code is one of the greatest discoveries of the 20th century as it is central to life itself. It is the algorithm that connects 64 RNA triplets to 20 amino acids, thus functioning as the Rosetta Stone of molecular biology.

Following the discovery of the structure of DNA by James Watson and Francis Crick in 1953, George Gamow organized the 20-member “RNA Tie Club” to discuss the transmission of information by DNA. Crick, Sydney Brenner, Leslie Barnett, and Richard Watts-Tobin first demonstrated the three bases of DNA code for one amino acid. The decoding of the genetic code was begun by Marshall Nirenberg and Heinrich Matthaei and was finally completed by Har Gobind Khorana.

In the mid-1960s, Carl Woese proposed the “stereochemical hypothesis”, which speculated that the genetic code derives from a type of codon–amino acid-pairing interaction. On the other hand, Crick proposed the “frozen accident hypothesis” and conjectured that the genetic code evolved from the last common universal ancestor and was frozen once established. However, he explicitly left room for stereochemical interactions between amino acids and their coding nucleotides, stating that “It is therefore essential to pursue the stereochemical theory…vague models of such interactions are of little use. What is wanted is direct experimental proof that these interactions take place…and some idea of their specificity.”

The origin and evolution of the genetic code remains a mystery despite numerous theories and attempts to understand these. In this Special Issue, experts in the field will present their thoughts and views on this topic. The scope of this Special Issue shall encompass not only experimental analyses, but also hypotheses and theoretical trials. Additionally, because 2016 commemorates the 100th anniversary of the birth of Francis Crick, the discoverer of the genetic code, historical commentaries on him are also welcome.

Prof. Dr. Koji Tamura
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Life is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • genetic code
  • stereochemistry
  • frozen accident
  • codon
  • anticodon
  • amino acid
  • tRNA
  • aminoacyl tRNA synthetase
  • specificity
  • Francis Crick

Published Papers (12 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Editorial

Jump to: Research, Review, Other

1229 KiB  
Editorial
The Genetic Code: Francis Crick’s Legacy and Beyond
by Koji Tamura
Life 2016, 6(3), 36; https://doi.org/10.3390/life6030036 - 25 Aug 2016
Cited by 7 | Viewed by 8490
Abstract
Francis Crick (Figure 1) was born on 8 June 1916, in Northampton, England, and passed away on 28 July 2004, in La Jolla, California, USA.[...] Full article
Show Figures

Figure 1

Research

Jump to: Editorial, Review, Other

20 pages, 607 KiB  
Article
Intrinsic Properties of tRNA Molecules as Deciphered via Bayesian Network and Distribution Divergence Analysis
by Sergio Branciamore, Grigoriy Gogoshin, Massimo Di Giulio and Andrei S. Rodin
Life 2018, 8(1), 5; https://doi.org/10.3390/life8010005 - 8 Feb 2018
Cited by 5 | Viewed by 4343
Abstract
The identity/recognition of tRNAs, in the context of aminoacyl tRNA synthetases (and other molecules), is a complex phenomenon that has major implications ranging from the origins and evolution of translation machinery and genetic code to the evolution and speciation of tRNAs themselves to [...] Read more.
The identity/recognition of tRNAs, in the context of aminoacyl tRNA synthetases (and other molecules), is a complex phenomenon that has major implications ranging from the origins and evolution of translation machinery and genetic code to the evolution and speciation of tRNAs themselves to human mitochondrial diseases to artificial genetic code engineering. Deciphering it via laboratory experiments, however, is difficult and necessarily time- and resource-consuming. In this study, we propose a mathematically rigorous two-pronged in silico approach to identifying and classifying tRNA positions important for tRNA identity/recognition, rooted in machine learning and information-theoretic methodology. We apply Bayesian Network modeling to elucidate the structure of intra-tRNA-molecule relationships, and distribution divergence analysis to identify meaningful inter-molecule differences between various tRNA subclasses. We illustrate the complementary application of these two approaches using tRNA examples across the three domains of life, and identify and discuss important (informative) positions therein. In summary, we deliver to the tRNA research community a novel, comprehensive methodology for identifying the specific elements of interest in various tRNA molecules, which can be followed up by the corresponding experimental work and/or high-resolution position-specific statistical analyses. Full article
Show Figures

Figure 1

2238 KiB  
Article
Bioinformatic Analysis Reveals Archaeal tRNATyr and tRNATrp Identities in Bacteria
by Takahito Mukai, Noah M. Reynolds, Ana Crnković and Dieter Söll
Life 2017, 7(1), 8; https://doi.org/10.3390/life7010008 - 21 Feb 2017
Cited by 16 | Viewed by 8095
Abstract
The tRNA identity elements for some amino acids are distinct between the bacterial and archaeal domains. Searching in recent genomic and metagenomic sequence data, we found some candidate phyla radiation (CPR) bacteria with archaeal tRNA identity for Tyr-tRNA and Trp-tRNA synthesis. These bacteria [...] Read more.
The tRNA identity elements for some amino acids are distinct between the bacterial and archaeal domains. Searching in recent genomic and metagenomic sequence data, we found some candidate phyla radiation (CPR) bacteria with archaeal tRNA identity for Tyr-tRNA and Trp-tRNA synthesis. These bacteria possess genes for tyrosyl-tRNA synthetase (TyrRS) and tryptophanyl-tRNA synthetase (TrpRS) predicted to be derived from DPANN superphylum archaea, while the cognate tRNATyr and tRNATrp genes reveal bacterial or archaeal origins. We identified a trace of domain fusion and swapping in the archaeal-type TyrRS gene of a bacterial lineage, suggesting that CPR bacteria may have used this mechanism to create diverse proteins. Archaeal-type TrpRS of bacteria and a few TrpRS species of DPANN archaea represent a new phylogenetic clade (named TrpRS-A). The TrpRS-A open reading frames (ORFs) are always associated with another ORF (named ORF1) encoding an unknown protein without global sequence identity to any known protein. However, our protein structure prediction identified a putative HIGH-motif and KMSKS-motif as well as many α-helices that are characteristic of class I aminoacyl-tRNA synthetase (aaRS) homologs. These results provide another example of the diversity of molecular components that implement the genetic code and provide a clue to the early evolution of life and the genetic code. Full article
Show Figures

Figure 1

621 KiB  
Article
On the Uniqueness of the Standard Genetic Code
by Gabriel S. Zamudio and Marco V. José
Life 2017, 7(1), 7; https://doi.org/10.3390/life7010007 - 13 Feb 2017
Cited by 11 | Viewed by 5235
Abstract
In this work, we determine the biological and mathematical properties that are sufficient and necessary to uniquely determine both the primeval RNY (purine-any base-pyrimidine) code and the standard genetic code (SGC). These properties are: the evolution of the SGC from the RNY code; [...] Read more.
In this work, we determine the biological and mathematical properties that are sufficient and necessary to uniquely determine both the primeval RNY (purine-any base-pyrimidine) code and the standard genetic code (SGC). These properties are: the evolution of the SGC from the RNY code; the degeneracy of both codes, and the non-degeneracy of the assignments of aminoacyl-tRNA synthetases (aaRSs) to amino acids; the wobbling property; the consideration that glycine was the first amino acid; the topological and symmetrical properties of both codes. Full article
Show Figures

Figure 1

Review

Jump to: Editorial, Research, Other

8716 KiB  
Review
Self-Referential Encoding on Modules of Anticodon Pairs—Roots of the Biological Flow System
by Romeu Cardoso Guimarães
Life 2017, 7(2), 16; https://doi.org/10.3390/life7020016 - 6 Apr 2017
Cited by 24 | Viewed by 7394
Abstract
The proposal that the genetic code was formed on the basis of (proto)tRNA Dimer-Directed Protein Synthesis is reviewed and updated. The tRNAs paired through the anticodon loops are an indication on the process. Dimers are considered mimics of the ribosomes—structures that hold tRNAs [...] Read more.
The proposal that the genetic code was formed on the basis of (proto)tRNA Dimer-Directed Protein Synthesis is reviewed and updated. The tRNAs paired through the anticodon loops are an indication on the process. Dimers are considered mimics of the ribosomes—structures that hold tRNAs together and facilitate the transferase reaction, and of the translation process—anticodons are at the same time codons for each other. The primitive protein synthesis system gets stabilized when the product peptides are stable and apt to bind the producers therewith establishing a self-stimulating production cycle. The chronology of amino acid encoding starts with Glycine and Serine, indicating the metabolic support of the Glycine-Serine C1-assimilation pathway, which is also consistent with evidence on origins of bioenergetics mechanisms. Since it is not possible to reach for substrates simpler than C1 and compounds in the identified pathway are apt for generating the other central metabolic routes, it is considered that protein synthesis is the beginning and center of a succession of sink-effective mechanisms that drive the formation and evolution of the metabolic flow system. Plasticity and diversification of proteins construct the cellular system following the orientation given by the flow and implementing it. Nucleic acid monomers participate in bioenergetics and the polymers are conservative memory systems for the synthesis of proteins. Protoplasmic fission is the final sink-effective mechanism, part of cell reproduction, guaranteeing that proteins don’t accumulate to saturation, which would trigger inhibition. Full article
Show Figures

Graphical abstract

2350 KiB  
Review
The Genetic Code and RNA-Amino Acid Affinities
by Michael Yarus
Life 2017, 7(2), 13; https://doi.org/10.3390/life7020013 - 23 Mar 2017
Cited by 58 | Viewed by 13568
Abstract
A significant part of the genetic code likely originated via a chemical interaction, which should be experimentally verifiable. One possible verification relates bound amino acids (or perhaps their activated congeners) and ribonucleotide sequences within cognate RNA binding sites. To introduce this interaction, I [...] Read more.
A significant part of the genetic code likely originated via a chemical interaction, which should be experimentally verifiable. One possible verification relates bound amino acids (or perhaps their activated congeners) and ribonucleotide sequences within cognate RNA binding sites. To introduce this interaction, I first summarize how amino acids function as targets for RNA binding. Then the experimental method for selecting relevant RNA binding sites is characterized. The selection method’s characteristics are related to the investigation of the RNA binding site model treated at the outset. Finally, real binding sites from selection and also from extant natural RNAs (for example, the Sulfobacillus guanidinium riboswitch) are connected to the genetic code, and by extension, to the evolutionary progression that produced the code. During this process, peptides may have been produced directly on an instructive amino acid binding RNA (a DRT; Direct RNA Template). Combination of observed stereochemical selectivity with adaptation and co-evolutionary refinement is logically required, and also potentially sufficient, to create the striking order conserved throughout the present coding table. Full article
Show Figures

Figure 1

2872 KiB  
Review
Efforts and Challenges in Engineering the Genetic Code
by Xiao Lin, Allen Chi Shing Yu and Ting Fung Chan
Life 2017, 7(1), 12; https://doi.org/10.3390/life7010012 - 14 Mar 2017
Cited by 13 | Viewed by 6935
Abstract
This year marks the 48th anniversary of Francis Crick’s seminal work on the origin of the genetic code, in which he first proposed the “frozen accident” hypothesis to describe evolutionary selection against changes to the genetic code that cause devastating global proteome modification. [...] Read more.
This year marks the 48th anniversary of Francis Crick’s seminal work on the origin of the genetic code, in which he first proposed the “frozen accident” hypothesis to describe evolutionary selection against changes to the genetic code that cause devastating global proteome modification. However, numerous efforts have demonstrated the viability of both natural and artificial genetic code variations. Recent advances in genetic engineering allow the creation of synthetic organisms that incorporate noncanonical, or even unnatural, amino acids into the proteome. Currently, successful genetic code engineering is mainly achieved by creating orthogonal aminoacyl-tRNA/synthetase pairs to repurpose stop and rare codons or to induce quadruplet codons. In this review, we summarize the current progress in genetic code engineering and discuss the challenges, current understanding, and future perspectives regarding genetic code modification. Full article
Show Figures

Figure 1

772 KiB  
Review
Future of the Genetic Code
by Hong Xue and J. Tze-Fei Wong
Life 2017, 7(1), 10; https://doi.org/10.3390/life7010010 - 28 Feb 2017
Cited by 4 | Viewed by 5428
Abstract
The methods for establishing synthetic lifeforms with rewritten genetic codes comprising non-canonical amino acids (NCAA) in addition to canonical amino acids (CAA) include proteome-wide replacement of CAA, insertion through suppression of nonsense codon, and insertion via the pyrrolysine and selenocysteine pathways. Proteome-wide reassignments [...] Read more.
The methods for establishing synthetic lifeforms with rewritten genetic codes comprising non-canonical amino acids (NCAA) in addition to canonical amino acids (CAA) include proteome-wide replacement of CAA, insertion through suppression of nonsense codon, and insertion via the pyrrolysine and selenocysteine pathways. Proteome-wide reassignments of nonsense codons and sense codons are also under development. These methods enable the application of NCAAs to enrich both fundamental and applied aspects of protein chemistry and biology. Sense codon reassignment to NCAA could incur problems arising from the usage of anticodons as identity elements on tRNA, and possible misreading of NNY codons by UNN anticodons. Evidence suggests that the problem of anticodons as identity elements can be diminished or resolved through removal from the tRNA of all identity elements besides the anticodon, and the problem of misreading of NNY codons by UNN anticodon can be resolved by the retirement of both the UNN anticodon and its complementary NNA codon from the proteome in the event that a restrictive post-transcriptional modification of the UNN anticodon by host enzymes to prevent the misreading cannot be obtained. Full article
Show Figures

Figure 1

7232 KiB  
Review
Homocysteine Editing, Thioester Chemistry, Coenzyme A, and the Origin of Coded Peptide Synthesis †
by Hieronim Jakubowski
Life 2017, 7(1), 6; https://doi.org/10.3390/life7010006 - 9 Feb 2017
Cited by 27 | Viewed by 8332
Abstract
Aminoacyl-tRNA synthetases (AARSs) have evolved “quality control” mechanisms which prevent tRNA aminoacylation with non-protein amino acids, such as homocysteine, homoserine, and ornithine, and thus their access to the Genetic Code. Of the ten AARSs that possess editing function, five edit homocysteine: Class I [...] Read more.
Aminoacyl-tRNA synthetases (AARSs) have evolved “quality control” mechanisms which prevent tRNA aminoacylation with non-protein amino acids, such as homocysteine, homoserine, and ornithine, and thus their access to the Genetic Code. Of the ten AARSs that possess editing function, five edit homocysteine: Class I MetRS, ValRS, IleRS, LeuRS, and Class II LysRS. Studies of their editing function reveal that catalytic modules of these AARSs have a thiol-binding site that confers the ability to catalyze the aminoacylation of coenzyme A, pantetheine, and other thiols. Other AARSs also catalyze aminoacyl-thioester synthesis. Amino acid selectivity of AARSs in the aminoacyl thioesters formation reaction is relaxed, characteristic of primitive amino acid activation systems that may have originated in the Thioester World. With homocysteine and cysteine as thiol substrates, AARSs support peptide bond synthesis. Evolutionary origin of these activities is revealed by genomic comparisons, which show that AARSs are structurally related to proteins involved in coenzyme A/sulfur metabolism and non-coded peptide bond synthesis. These findings suggest that the extant AARSs descended from ancestral forms that were involved in non-coded Thioester-dependent peptide synthesis, functionally similar to the present-day non-ribosomal peptide synthetases. Full article
Show Figures

Figure 1

Other

1005 KiB  
Concept Paper
Frozen Accident Pushing 50: Stereochemistry, Expansion, and Chance in the Evolution of the Genetic Code
by Eugene V. Koonin
Life 2017, 7(2), 22; https://doi.org/10.3390/life7020022 - 23 May 2017
Cited by 57 | Viewed by 11046
Abstract
Nearly 50 years ago, Francis Crick propounded the frozen accident scenario for the evolution of the genetic code along with the hypothesis that the early translation system consisted primarily of RNA. Under the frozen accident perspective, the code is universal among modern life [...] Read more.
Nearly 50 years ago, Francis Crick propounded the frozen accident scenario for the evolution of the genetic code along with the hypothesis that the early translation system consisted primarily of RNA. Under the frozen accident perspective, the code is universal among modern life forms because any change in codon assignment would be highly deleterious. The frozen accident can be considered the default theory of code evolution because it does not imply any specific interactions between amino acids and the cognate codons or anticodons, or any particular properties of the code. The subsequent 49 years of code studies have elucidated notable features of the standard code, such as high robustness to errors, but failed to develop a compelling explanation for codon assignments. In particular, stereochemical affinity between amino acids and the cognate codons or anticodons does not seem to account for the origin and evolution of the code. Here, I expand Crick’s hypothesis on RNA-only translation system by presenting evidence that this early translation already attained high fidelity that allowed protein evolution. I outline an experimentally testable scenario for the evolution of the code that combines a distinct version of the stereochemical hypothesis, in which amino acids are recognized via unique sites in the tertiary structure of proto-tRNAs, rather than by anticodons, expansion of the code via proto-tRNA duplication, and the frozen accident. Full article
Show Figures

Figure 1

379 KiB  
Concept Paper
What Froze the Genetic Code?
by Lluís Ribas de Pouplana, Adrian Gabriel Torres and Àlbert Rafels-Ybern
Life 2017, 7(2), 14; https://doi.org/10.3390/life7020014 - 5 Apr 2017
Cited by 17 | Viewed by 5594
Abstract
The frozen accident theory of the Genetic Code was a proposal by Francis Crick that attempted to explain the universal nature of the Genetic Code and the fact that it only contains information for twenty amino acids. Fifty years later, it is clear [...] Read more.
The frozen accident theory of the Genetic Code was a proposal by Francis Crick that attempted to explain the universal nature of the Genetic Code and the fact that it only contains information for twenty amino acids. Fifty years later, it is clear that variations to the universal Genetic Code exist in nature and that translation is not limited to twenty amino acids. However, given the astonishing diversity of life on earth, and the extended evolutionary time that has taken place since the emergence of the extant Genetic Code, the idea that the translation apparatus is for the most part immobile remains true. Here, we will offer a potential explanation to the reason why the code has remained mostly stable for over three billion years, and discuss some of the mechanisms that allow species to overcome the intrinsic functional limitations of the protein synthesis machinery. Full article
Show Figures

Figure 1

3134 KiB  
Opinion
Piecemeal Buildup of the Genetic Code, Ribosomes, and Genomes from Primordial tRNA Building Blocks
by Derek Caetano-Anollés and Gustavo Caetano-Anollés
Life 2016, 6(4), 43; https://doi.org/10.3390/life6040043 - 2 Dec 2016
Cited by 26 | Viewed by 8314
Abstract
The origin of biomolecular machinery likely centered around an ancient and central molecule capable of interacting with emergent macromolecular complexity. tRNA is the oldest and most central nucleic acid molecule of the cell. Its co-evolutionary interactions with aminoacyl-tRNA synthetase protein enzymes define the [...] Read more.
The origin of biomolecular machinery likely centered around an ancient and central molecule capable of interacting with emergent macromolecular complexity. tRNA is the oldest and most central nucleic acid molecule of the cell. Its co-evolutionary interactions with aminoacyl-tRNA synthetase protein enzymes define the specificities of the genetic code and those with the ribosome their accurate biosynthetic interpretation. Phylogenetic approaches that focus on molecular structure allow reconstruction of evolutionary timelines that describe the history of RNA and protein structural domains. Here we review phylogenomic analyses that reconstruct the early history of the synthetase enzymes and the ribosome, their interactions with RNA, and the inception of amino acid charging and codon specificities in tRNA that are responsible for the genetic code. We also trace the age of domains and tRNA onto ancient tRNA homologies that were recently identified in rRNA. Our findings reveal a timeline of recruitment of tRNA building blocks for the formation of a functional ribosome, which holds both the biocatalytic functions of protein biosynthesis and the ability to store genetic memory in primordial RNA genomic templates. Full article
Show Figures

Figure 1

Back to TopTop