The genetic code.
Ontology highlight
ABSTRACT:
SUBMITTER: Marshall J
PROVIDER: S-EPMC4000838 | biostudies-literature | 2014 Apr
REPOSITORIES: biostudies-literature
Publications
The genetic code.
Proceedings of the National Academy of Sciences of the United States of America 20140401 16
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Project description: Not available
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Project description: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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Project description:When using a compacted version of the "I Ching" genetic code, the number of symbols is reduced to only 8 symbolic binary constants, integrated by only three symbols, being each: either the continuous or the broken horizontal line, plus the respective one word abbreviations of their resulting amino acids, namely, between four to eight accompanying the triad of lines, giving a total set of 46 possible combinations. This study is an alternate way of file compression for the genetic code, focused in the nucleotides, while another one I explored elsewhere, was focused in the groupings of amino acids, both individually and by their codon equivalents. As an Appendix 1 & 2 analogy, I add an example of "mutations" in literature, based on two early versions of "The Fair" (in its first edition of 1963, and in its first red edition of 1971), comparing its vignettes, and written in Spanish by my professor Juan José Arreola, now at his 101 year of birth.
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Project description:Expanding the genetic code to enable the incorporation of unnatural amino acids into proteins in biological systems provides a powerful tool for studying protein structure and function. While this technology has been mostly developed and applied in bacterial and mammalian cells, it recently expanded into animals, including worms, fruit flies, zebrafish, and mice. In this review, we highlight recent advances toward the methodology development of genetic code expansion in animal model organisms. We further illustrate the applications, including proteomic labeling in fruit flies and mice and optical control of protein function in mice and zebrafish. We summarize the challenges of unnatural amino acid mutagenesis in animals and the promising directions toward broad application of this emerging technology.
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Project description:#1. Bottom-up data of ALDOA-K147 purified protein ALDOA-K147-purified-protein #2. Bottom-up data of IP-MS analysis of Klac and KlacOEt 20231016-DIA-IP-N1-con 20231016-DIA-IP-N2-con 20231016-DIA-IP-N3-con 20231016-DIA-IP-N1-Klac 20231016-DIA-IP-N2-Klac 20231016-DIA-IP-N3-Klac 20231016-DIA-IP-N1-KlacOEt 20231016-DIA-IP-N2-KlacOEt 20231016-DIA-IP-N3-KlacOEt 20231016-DDA-IP-con 20231016-DDA-IP-Klac 20231016-DDA-IP-KlacOEt 20231016-input-con 20231016-input-Klac 20231016-input-KlacOEt #3. TRAP analysis of ALDOA-WT and ALDOA-K147 20240307-TRAP-A1 20240307-TRAP-A2 20240307-TRAP-A3 20240307-TRAP-A4 20240307-TRAP-K1 20240307-TRAP-K2 20240307-TRAP-K3 20240307-TRAP-K4
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Project description:A dynamical theory for the evolution of the genetic code is presented, which accounts for its universality and optimality. The central concept is that a variety of collective, but non-Darwinian, mechanisms likely to be present in early communal life generically lead to refinement and selection of innovation-sharing protocols, such as the genetic code. Our proposal is illustrated by using a simplified computer model and placed within the context of a sequence of transitions that early life may have made, before the emergence of vertical descent.
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Project description:Genetic code expansion (GCE) is a versatile tool to site-specifically incorporate a noncanonical amino acid (ncAA) into a protein, for example, to perform fluorescent labeling inside living cells. To this end, an orthogonal aminoacyl-tRNA-synthetase/tRNA (RS/tRNA) pair is used to insert the ncAA in response to an amber stop codon in the protein of interest. One of the drawbacks of this system is that, in order to achieve maximum efficiency, high levels of the orthogonal tRNA are required, and this could interfere with host cell functionality. To minimize the adverse effects on the host, we have developed an inducible GCE system that enables us to switch on tRNA or RS expression when needed. In particular, we tested different promotors in the context of the T-REx or Tet-On systems to control expression of the desired orthogonal tRNA and/or RS. We discuss our result with respect to the control of GCE components as well as efficiency. We found that only the T-REx system enables simultaneous control of tRNA and RS expression.
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Project description:A near-universal Standard Genetic Code (SGC) implies a single origin for present Earth life. To study this unique event, I compute paths to the SGC, comparing different plausible histories. Notably, SGC-like coding emerges from traditional evolutionary mechanisms, and a superior route can be identified. To objectively measure evolution, progress values from 0 (random coding) to 1 (SGC-like) are defined: these measure fractions of random-code-to-SGC distance. Progress types are spacing/distance/delta Polar Requirement, detecting space between identical assignments/mutational distance to the SGC/chemical order, respectively. The coding system is based on selected RNAs performing aminoacyl-RNA synthetase reactions. Acceptor RNAs exhibit SGC-like Crick wobble; alternatively, non-wobbling triplets uniquely encode 20 amino acids/start/stop. Triplets acquire 22 functions by stereochemistry, selection, coevolution, or at random. Assignments also propagate to an assigned triplet's neighborhood via single mutations, but can also decay. A vast code universe makes futile evolutionary paths plentiful. Thus, SGC evolution is critically sensitive to disorder from random assignments. Evolution also inevitably slows near coding completion. The SGC likely avoided these difficulties, and two suitable paths are compared. In late wobble, a majority of non-wobble assignments are made before wobble is adopted. In continuous wobble, a uniquely advantageous early intermediate yields an ordered SGC. Revised coding evolution (limited randomness, late wobble, concentration on amino acid encoding, chemically conservative coevolution with a chemically ordered elite) produces varied full codes with excellent joint progress values. A population of only 600 independent coding tables includes SGC-like members; a Bayesian path toward more accurate SGC evolution is available.
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Project description:Selenocysteine (Sec) is naturally incorporated into proteins by recoding the stop codon UGA. Sec is not hardwired to UGA, as the Sec insertion machinery was found to be able to site-specifically incorporate Sec directed by 58 of the 64 codons. For 15 sense codons, complete conversion of the codon meaning from canonical amino acid (AA) to Sec was observed along with a tenfold increase in selenoprotein yield compared to Sec insertion at the three stop codons. This high-fidelity sense-codon recoding mechanism was demonstrated for Escherichia coli formate dehydrogenase and recombinant human thioredoxin reductase and confirmed by independent biochemical and biophysical methods. Although Sec insertion at UGA is known to compete against protein termination, it is surprising that the Sec machinery has the ability to outcompete abundant aminoacyl-tRNAs in decoding sense codons. The findings have implications for the process of translation and the information storage capacity of the biological cell.
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Project description:Several hypotheses predict ranks of amino acid assignments to genetic code's codons. Analyses here show that average positions of amino acid species in proteins correspond to assignment ranks, in particular as predicted by Juke's neutral mutation hypothesis for codon assignments. In all tested protein groups, including co- and post-translationally folding proteins, 'recent' amino acids are on average closer to gene 5' extremities than 'ancient' ones. Analyses of pairwise residue contact energies matrices suggest that early amino acids stereochemically selected late ones that stablilize residue interactions within protein cores, presumably producing 5'-late-to-3'-early amino acid protein sequence gradients. The gradient might reduce protein misfolding, also after mutations, extending principles of neutral mutations to protein folding. Presumably, in self-perpetuating and self-correcting systems like the genetic code, initial conditions produce similarities between evolution of the process (the genetic code) and 'ontogeny' of resulting structures (here proteins), producing apparent teleonomy between process and product.
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