The Experts below are selected from a list of 294 Experts worldwide ranked by ideXlab platform
Massimo Di Giulio - One of the best experts on this subject based on the ideXlab platform.
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The origin of the Genetic Code and origin of ideas.
Journal of theoretical biology, 2021Co-Authors: Massimo Di GiulioAbstract:Abstract Inouye et al. (2020) use the observation that Ser is Coded in the Genetic Code by two blocks of codons that differ on more than one base to understand some aspects of the origin of the Genetic Code organization. I argue instead that this observation per se cannot be used to understand any aspect of the origin of the Genetic Code, unless it is accompanied by other assumptions concerning in the specific case: (i) the ancestrality of some amino acids, (ii) the hypothesis that the first mRNA to be translated was poly-G, which can be translated into poly-Gly, and (iii) an evolutionary mechanism for the Genetic Code origin based on the duplication of tRNAs. However, both the tRNA duplication mechanism and the existence of poly-G as the first mRNA to be translated are not corroborated as mechanisms through which the Genetic Code would have been structured. For example, the origin of the actual mRNA should have been preceded by the evolution of a proto-mRNA which evidently already Coded for more than one amino acid. Therefore, when it evolved from proto-mRNA, the mRNA should already have Coded for more than one amino acid. In other words, poly-G as mRNA would most likely never have existed because the first mRNAs already had to Code for more than one amino acid. On the contrary, all these assumptions would have been operational if the observations of Inouye et al. (2020) had been discussed within the coevolution theory of the origin of the Genetic Code, which they do not.
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A methanogen hosted the origin of the Genetic Code
Journal of Theoretical Biology, 2009Co-Authors: Massimo Di GiulioAbstract:A comparison is made between orthologous proteins from a methanogen () and from a non-methanogen ( in order to determine the amino acid substitution pattern. This analysis makes it possible to establish which amino acids are significantly and asymmetrically utilised by these two organisms. A methanophily index (MI) based on this asymmetry makes it possible for any protein to be associated with a numerical value which, when calculated for the same orthologous protein from methanogenic and non-methanogenic organisms, turns out to have the power to discriminate between these two groups of organisms, even if only for about 20% of the analysed proteins. The MI can also be associated to the Genetic Code under the assumption that the frequency of synonymous codons specifying the amino acids in the Genetic Code also reflects the frequency with which amino acids appeared in ancestral proteins. Finally a t test shows that the MI value associated to the Genetic Code is not different from the mean value of the MI deriving from methanogen proteins, but it differs from the mean MI of non-methanogen proteins. This might indicate that the Genetic Code evolved in a methanogenic ‘organism'.
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A methanogen hosted the origin of the Genetic Code.
Journal of theoretical biology, 2009Co-Authors: Massimo Di GiulioAbstract:A comparison is made between orthologous proteins from a methanogen (Methanopyrus kandleri) and from a non-methanogen (Pyrococcus abyssi) in order to determine the amino acid substitution pattern. This analysis makes it possible to establish which amino acids are significantly and asymmetrically utilised by these two organisms. A methanophily index (MI) based on this asymmetry makes it possible for any protein to be associated with a numerical value which, when calculated for the same orthologous protein from methanogenic and non-methanogenic organisms, turns out to have the power to discriminate between these two groups of organisms, even if only for about 20% of the analysed proteins. The MI can also be associated to the Genetic Code under the assumption that the frequency of synonymous codons specifying the amino acids in the Genetic Code also reflects the frequency with which amino acids appeared in ancestral proteins. Finally a t-test shows that the MI value associated to the Genetic Code is not different from the mean value of the MI deriving from methanogen proteins, but it differs from the mean MI of non-methanogen proteins. This might indicate that the Genetic Code evolved in a methanogenic 'organism'.
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The ocean abysses witnessed the origin of the Genetic Code
Gene, 2004Co-Authors: Massimo Di GiulioAbstract:The comparison of proteins from a non-barophilous and a barophilous organism makes it possible to define the barophily ranks of amino acids. The correlation of these ranks with the number of codons attributed to amino acids in the Genetic Code, together with another straightforward argument based on an optimisation percentage of a barophily index (BI) (easily defined by barophily ranks) which can be associated to the Genetic Code table, suggest that the Genetic Code originated under high hydrostatic pressure. Moreover, as the BI value can be calculated for the sequence of any protein, it also makes it possible to define the BI for the Genetic Code if the number of codons attributed to the amino acids in the Code is assumed to be the frequency with which the amino acids appeared in ancestral proteins. Finally, sampling the BI variable between many non-barophile organisms and from many proteins of a single non-barophile organism leads to the conclusion that the BI value of the Genetic Code is not typical of these organisms. Whereas, since the Genetic Code BI value is statistically higher than that of these non-barophile organisms, it supports the hypothesis that Genetic Code structuring took place under high hydrostatic pressure.
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The origin of the Genetic Code: theories and their relationships, a review.
Bio Systems, 2004Co-Authors: Massimo Di GiulioAbstract:A review of the main theories proposed to explain the origin of the Genetic Code is presented. I analyze arguments and data in favour of different theories proposed to explain the origin of the organization of the Genetic Code. It is possible to suggest a mechanism that makes compatible the different theories of the origin of the Code, even if these are based on a historical or physicochemical determinism and thus appear incompatible by definition. Finally, I discuss the question of why a given number of synonymous codons was attributed to the amino acids in the Genetic Code.
Dieter Söll - One of the best experts on this subject based on the ideXlab platform.
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Rewriting the Genetic Code
Annual review of microbiology, 2017Co-Authors: Takahito Mukai, Marc J. Lajoie, Markus Englert, Dieter SöllAbstract:The Genetic Code-the language used by cells to translate their genomes into proteins that perform many cellular functions-is highly conserved throughout natural life. Rewriting the Genetic Code could lead to new biological functions such as expanding protein chemistries with noncanonical amino acids (ncAAs) and Genetically isolating synthetic organisms from natural organisms and viruses. It has long been possible to transiently produce proteins bearing ncAAs, but stabilizing an expanded Genetic Code for sustained function in vivo requires an integrated approach: creating reCoded genomes and introducing new translation machinery that function together without compromising viability or clashing with endogenous pathways. In this review, we discuss design considerations and technologies for expanding the Genetic Code. The knowledge obtained by rewriting the Genetic Code will deepen our understanding of how genomes are designed and how the canonical Genetic Code evolved.
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Overcoming Challenges in Engineering the Genetic Code.
Journal of Molecular Biology, 2016Co-Authors: Marc J. Lajoie, Dieter Söll, George M. ChurchAbstract:Withstanding 3.5 billion years of Genetic drift, the canonical Genetic Code remains such a fundamental foundation for the complexity of life that it is highly conserved across all three phyloGenetic domains. Genome engineering technologies are now making it possible to rationally change the Genetic Code, offering resistance to viruses, Genetic isolation from horizontal gene transfer, and prevention of environmental escape by Genetically modified organisms. We discuss the biochemical, Genetic, and technological challenges that must be overcome in order to engineer the Genetic Code.
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Genetic Code flexibility in microorganisms novel mechanisms and impact on physiology
Nature Reviews Microbiology, 2015Co-Authors: Jiqiang Ling, Patrick Odonoghue, Dieter SöllAbstract:The Genetic Code, initially thought to be universal and immutable, is now known to contain many variations, including biased codon usage, codon reassignment, ambiguous decoding and recoding. As a result of recent advances in the areas of genome sequencing, biochemistry, bioinformatics and structural biology, our understanding of Genetic Code flexibility has advanced substantially in the past decade. In this Review, we highlight the prevalence, evolution and mechanistic basis of Genetic Code variations in microorganisms, and we discuss how this flexibility of the Genetic Code affects microbial physiology.
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The Genetic Code: Yesterday, today, and tomorrow
Resonance, 2012Co-Authors: Jiqiang Ling, Dieter SöllAbstract:This issue is a tribute to Har Gobind Khorana who received the Nobel Prize in Physiology or Medicine in 1968 for the elucidation of the Genetic Code. Here we present our view of the changing and ever-challenging perception of the Genetic Code over the last 50 years.
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natural expansion of the Genetic Code
Nature Chemical Biology, 2007Co-Authors: Alexandre Ambrogelly, Sotiria Palioura, Dieter SöllAbstract:At the time of its discovery four decades ago, the Genetic Code was viewed as the result of a “frozen accident.” Our current knowledge of the translation process and of the detailed structure of its components highlights the roles of RNA structure (in mRNA and tRNA), RNA modification (in tRNA), and aminoacyl-tRNA synthetase diversity in the evolution of the Genetic Code. The diverse assortment of codon reassignments present in subcellular organelles and organisms of distinct lineages has 'thawed' the concept of a universal immutable Code; it may not be accidental that out of more than 140 amino acids found in natural proteins, only two (selenocysteine and pyrrolysine) are known to have been added to the standard 20-member amino acid alphabet. The existence of phosphoseryl-tRNA (in the form of tRNACys and tRNASec) may presage the discovery of other cotranslationally inserted modified amino acids.
Jason W Chin - One of the best experts on this subject based on the ideXlab platform.
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reprogramming the Genetic Code
Science, 2012Co-Authors: Jason W ChinAbstract:The Genetic Code provides rules by which a genome is deCoded to produce proteins of defined amino acid composition and sequence. These rules, which specify 61 codons (triplets of nucleotides) that Code for the 20 common amino acids, and 3 codons that signal the termination of protein synthesis, are near-universally conserved in living organisms. Despite conservation of this Code and the translational machinery that enforces it, a growing body of work addresses the challenges in reprogramming the Genetic Code. Designer amino acids, created by synthetic chemistry, can now be incorporated into specific sites in proteins of interest in vitro, in cells, and most recently in a whole animal (see the figure). These routes to unnatural polymer synthesis and evolution are already facilitating the study of cellular processes including protein interactions, protein conformational changes, posttranslational modification biology, and the kinetics of protein transport and cell signaling with a new level of molecular precision ( 1 ). Emerging developments may allow the synthesis and evolution of new materials and therapeutics.
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Expanding the Genetic Code of an Animal
Journal of the American Chemical Society, 2011Co-Authors: Sebastian Greiss, Jason W ChinAbstract:Genetic Code expansion, for the site-specific incorporation of unnatural amino acids into proteins, is currently limited to cultured cells and unicellular organisms. Here we expand the Genetic Code of a multicellular animal, the nematode Caenorhabditis elegans.
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An expanded eukaryotic Genetic Code
Science, 2003Co-Authors: Jason W Chin, T. Ashton Cropp, Mridul Mukherji, J. Christopher Anderson, Zhiwen Zhang, P. G. SchultzAbstract:We describe a general and rapid route for the addition of unnatural amino acids to the Genetic Code of Saccharomyces cerevisiae. Five amino acids have been incorporated into proteins efficiently and with high fidelity in response to the nonsense codon TAG. The side chains of these amino acids contain a keto group, which can be uniquely modified in vitro and in vivo with a wide range of chemical probes and reagents; a heavy atom-containing amino acid for structural studies; and photocrosslinkers for cellular studies of protein interactions. This methodology not only removes the constraints imposed by the Genetic Code on our ability to manipulate protein structure and function in yeast, it provides a gateway to the systematic expansion of the Genetic Codes of multicellular eukaryotes.
Nediljko Budisa - One of the best experts on this subject based on the ideXlab platform.
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recent advances in Genetic Code engineering in escherichia coli
Current Opinion in Biotechnology, 2012Co-Authors: Michael Georg Hoesl, Nediljko BudisaAbstract:The expansion of the Genetic Code is gradually becoming a core discipline in Synthetic Biology. It offers the best possible platform for the transfer of numerous chemical reactions and processes from the chemical synthetic laboratory into the biochemistry of living cells. The incorporation of biologically occurring or chemically synthesized non-canonical amino acids into recombinant proteins and even proteomes via reprogrammed protein translation is in the heart of these efforts. Orthogonal pairs consisting of aminoacyl-tRNA synthetase and its cognate tRNA proved to be a general tool for the assignment of certain codons of the Genetic Code with a maximum degree of chemical liberty. Here, we highlight recent developments that should provide a solid basis for the development of generalist tools enabling a controlled variation of chemical composition in proteins and even proteomes. This will take place in the frame of a greatly expanded Genetic Code with emancipated codons liberated from the current function or with totally new coding units.
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Natural history and experimental evolution of the Genetic Code
Applied Microbiology and Biotechnology, 2007Co-Authors: Birgit Wiltschi, Nediljko BudisaAbstract:The standard Genetic Code is a set of rules that relates the 20 canonical amino acids in proteins to groups of three bases in the mRNA. It evolved from a more primitive form and the attempts to reconstruct its natural history are based on its present-day features. Genetic Code engineering as a new research field was developed independently in a few laboratories during the last 15 years. The main intention is to re-program protein synthesis by expanding the coding capacities of the Genetic Code via re-assignment of specific codons to un-natural amino acids. This article focuses on the question as to which extent hypothetical scenarios that led to codon re-assignments during the evolution of the Genetic Code are relevant for its further evolution in the laboratory. Current attempts to engineer the Genetic Code are reviewed with reference to theoretical works on its natural history. Integration of the theoretical considerations into experimental concepts will bring us closer to designer cells with target-engineered Genetic Codes that should open not only tremendous possibilities for the biotechnology of the twenty-first century but will also provide a basis for the design of novel life forms.
Hiroaki Suga - One of the best experts on this subject based on the ideXlab platform.
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flexizymes for Genetic Code reprogramming
Nature Protocols, 2011Co-Authors: Yuki Goto, Hiroaki Suga, Takayuki KatohAbstract:Genetic Code reprogramming is a method for the reassignment of arbitrary codons from proteinogenic amino acids to nonproteinogenic ones; thus, specific sequences of nonstandard peptides can be ribosomally expressed according to their mRNA templates. Here we describe a protocol that facilitates Genetic Code reprogramming using flexizymes integrated with a custom-made in vitro translation apparatus, referred to as the flexible in vitro translation (FIT) system. Flexizymes are flexible tRNA acylation ribozymes that enable the preparation of a diverse array of nonproteinogenic acyl-tRNAs. These acyl-tRNAs read vacant codons created in the FIT system, yielding the desired nonstandard peptides with diverse exotic structures, such as N-methyl amino acids, D-amino acids and physiologically stable macrocyclic scaffolds. The facility of the protocol allows a wide variety of applications in the synthesis of new classes of nonstandard peptides with biological functions. Preparation of flexizymes and tRNA used for Genetic Code reprogramming, optimization of flexizyme reaction conditions and expression of nonstandard peptides using the FIT system can be completed by one person in approximately 1 week. However, once the flexizymes and tRNAs are in hand and reaction conditions are fixed, synthesis of acyl-tRNAs and peptide expression is generally completed in 1 d, and alteration of a peptide sequence can be achieved by simply changing the corresponding mRNA template.
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Synthesis of biopolymers using Genetic Code reprogramming.
Current opinion in chemical biology, 2008Co-Authors: Atsushi Ohta, Yusuke Yamagishi, Hiroaki SugaAbstract:Genetic Code reprogramming is a new emerging methodology that enables us to synthesize non-standard peptides containing multiple non-proteinogenic amino acids using translation machinery. This review describes the historical background of this methodology and what distinguishes it from the classical 'nonsense suppression' methodology, followed by a discussion of recent developments in combining this methodology with other compatible technologies. Specifically, we discuss in detail the combination of Genetic Code reprogramming with flexizymes, de novo tRNA acylation ribozymes that facilitate the charging process of a variety of non-proteinogenic amino acids onto tRNAs bearing designated anticodons, and summarize some of the recent demonstrations of the synthesis of non-standard peptides with cyclic structure or/and altered backbones employing this technology.
