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Variations of these equations furnish a basis for comparing the plausibility of contrasting scenarios for the emergence of tRNA aminoacylation, ultimately by enzymes, and the relationship of this process with the origin of the universal system of molecular biological information processing embodied in the Central Dogma. The hypothetical RNA World does not furnish an adequate basis for explaining how this system came into being, but principles of self-organisation that transcend Darwinian natural selection furnish an unexpectedly robust basis for a rapid, concerted transition to genetic coding from a peptide-RNA world.","author":[{"@context":"https://schema.org","@type":"Person","name":"Charles Carter"}],"contributor":[],"dateCreated":"2021-10-16","dateModified":"2022-12-14","headline":"Insuperable Problems Of The Genetic Code Initially Emerging In An RNA World","image":"https://attachments.academia-assets.com/72866911/thumbnails/1.jpg","inLanguage":"en","keywords":["Engineering","RNA","Catalysis","Bio-Inspired Systems","Biological Sciences","Humans","Animals","Molecular Phylogenetics and Evolution","Genetic Code","Protein Biosynthesis"],"publisher":{"@context":"https://schema.org","@type":"Organization","name":"Cold Spring Harbor 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Variations of these equations furnish a basis for comparing the plausibility of contrasting scenarios for the emergence of tRNA aminoacylation, ultimately by enzymes, and the relationship of this process with the origin of the universal system of molecular biological information processing embodied in the Central Dogma. The hypothetical RNA World does not furnish an adequate basis for explaining how this system came into being, but principles of self-organisation that transcend Darwinian natural selection furnish an unexpectedly robust basis for a rapid, concerted transition to genetic coding from a peptide-RNA world.","publisher":"Cold Spring Harbor Laboratory"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"Insuperable Problems Of The Genetic Code Initially Emerging In An RNA World","broadcastable":true,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [23452151]; window.loswp.locale = "en"; window.loswp.countryCode = "SG"; window.loswp.cwvAbTestBucket = ""; window.loswp.designVariant = "ds_vanilla"; window.loswp.fullPageMobileSutdModalVariant = "full_page_mobile_sutd_modal"; window.loswp.useOptimizedScribd4genScript = false; window.loginModal = {}; window.loginModal.appleClientId = 'edu.academia.applesignon';</script><script defer="" src="https://accounts.google.com/gsi/client"></script><div class="ds-loswp-container"><div class="ds-work-card--grid-container"><div class="ds-work-card--container js-loswp-work-card"><div class="ds-work-card--cover"><div class="ds-work-cover--wrapper"><div class="ds-work-cover--container"><button class="ds-work-cover--clickable js-swp-download-button" data-signup-modal="{"location":"swp-splash-paper-cover","attachmentId":72866911,"attachmentType":"pdf"}"><img alt="First page of “Insuperable Problems Of The Genetic Code Initially Emerging In An RNA World”" class="ds-work-cover--cover-thumbnail" src="https://0.academia-photos.com/attachment_thumbnails/72866911/mini_magick20211016-25487-fnd40f.png?1634415390" /><img alt="PDF Icon" class="ds-work-cover--file-icon" src="//a.academia-assets.com/images/single_work_splash/adobe_icon.svg" /><div class="ds-work-cover--hover-container"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span><p>Download Free PDF</p></div><div class="ds-work-cover--ribbon-container">Download Free PDF</div><div class="ds-work-cover--ribbon-triangle"></div></button></div></div></div><div class="ds-work-card--work-information"><h1 class="ds-work-card--work-title">Insuperable Problems Of The Genetic Code Initially Emerging In An RNA World</h1><div class="ds-work-card--work-authors ds-work-card--detail"><a class="ds-work-card--author js-wsj-grid-card-author ds2-5-body-md ds2-5-body-link" data-author-id="23452151" href="https://unc.academia.edu/CharlesCarter"><img alt="Profile image of Charles Carter" class="ds-work-card--author-avatar" src="https://0.academia-photos.com/23452151/6359586/7195829/s65_charles.carter.jpg_oh_0094d962ff63926f062367d1aadfb694_oe_553f0d2c___gda___1425675621_d72cb35db3618fcca298b77b8391c0af" />Charles Carter</a></div><div class="ds-work-card--detail"><div class="ds-work-card--work-metadata"><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">visibility</span><p class="ds2-5-body-sm" id="work-metadata-view-count">…</p></div><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">description</span><p class="ds2-5-body-sm">23 pages</p></div><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">link</span><p class="ds2-5-body-sm">1 file</p></div></div><script>(async () => { const workId = 58472550; 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if (!viewCountBody) { throw new Error('Failed to find work views element'); } viewCountBody.textContent = `${commaizedViewCount} views`; } catch (error) { // Remove the whole views element if there was some issue parsing. document.getElementById('work-metadata-view-count')?.parentNode?.remove(); throw new Error(`Failed to parse view count: ${viewCount}`, error); } }; // If the DOM is still loading, wait for it to be ready before updating the view count. if (document.readyState === "loading") { document.addEventListener('DOMContentLoaded', () => { updateViewCount(viewCount); }); // Otherwise, just update it immediately. } else { updateViewCount(viewCount); } })();</script></div><p class="ds-work-card--work-abstract ds-work-card--detail ds2-5-body-md">Differential equations for error-prone information transfer (template replication, transcription or translation) are developed in order to consider, within the theory of autocatalysis, the advent of coded protein synthesis. Variations of these equations furnish a basis for comparing the plausibility of contrasting scenarios for the emergence of tRNA aminoacylation, ultimately by enzymes, and the relationship of this process with the origin of the universal system of molecular biological information processing embodied in the Central Dogma. The hypothetical RNA World does not furnish an adequate basis for explaining how this system came into being, but principles of self-organisation that transcend Darwinian natural selection furnish an unexpectedly robust basis for a rapid, concerted transition to genetic coding from a peptide-RNA world.</p><div class="ds-work-card--button-container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--work-card","attachmentId":72866911,"attachmentType":"pdf","workUrl":"https://www.academia.edu/58472550/Insuperable_Problems_Of_The_Genetic_Code_Initially_Emerging_In_An_RNA_World"}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--work-card","attachmentId":72866911,"attachmentType":"pdf","workUrl":"https://www.academia.edu/58472550/Insuperable_Problems_Of_The_Genetic_Code_Initially_Emerging_In_An_RNA_World"}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div></div></div><div data-auto_select="false" data-client_id="331998490334-rsn3chp12mbkiqhl6e7lu2q0mlbu0f1b" data-doc_id="72866911" data-landing_url="https://www.academia.edu/58472550/Insuperable_Problems_Of_The_Genetic_Code_Initially_Emerging_In_An_RNA_World" data-login_uri="https://www.academia.edu/registrations/google_one_tap" data-moment_callback="onGoogleOneTapEvent" id="g_id_onload"></div><div class="ds-top-related-works--grid-container"><div class="ds-related-content--container ds-top-related-works--container"><h2 class="ds-related-content--heading">Related papers</h2><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="0" data-entity-id="1899421" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/1899421/The_origin_of_the_genetic_code_and_protein_synthesis">The origin of the genetic code and protein synthesis</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="2410354" href="https://unich-it.academia.edu/SaverioAlberti">Saverio Alberti</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of molecular evolution, 1997</p><p class="ds-related-work--abstract ds2-5-body-sm">A model for a parallel evolution of the genetic code and protein synthesis is presented. The main tenet of this model is that the genetic code, that is, a correspondence between nucleotide and aminoacid coding units, originated from sequence-specific interaction between abiotically synthesized polynucleotides and polypeptides. A sequence-specific binding between oligonucleotides and oligopeptides is supported by experimental findings. Moreover, it is parsimonious enough to be consistent with the relatively simple chemistry of a primordial environment. Proximity between peptides and RNA increased the rate of formation of ester bonds between them. This lead to the accumulation of sequence-specific polypeptide-polynucleotide pairs, that is, of primordial-loaded tRNA. Condensation of short polypeptides into longer products could be catalyzed by a sequence-specific juxtaposition of loaded tRNA over complementary RNA, originating the core of protein synthesis. The accumulation of useful encoded products, for example, catalysts for tRNA loading (primordial aminoacyl-tRNA synthetases) or stabilizers of tRNA-mRNA interactions (primordial ribosomes), permitted the subsequent evolution of protein synthesis and of the genetic code to their mature form. This occurred via a parallel reduction in length of the interacting polynucleotides and polypeptides. Thus, it maintained the correct reading frame of mRNA from the preceding stages of evolution.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"The origin of the genetic code and protein synthesis","attachmentId":30393466,"attachmentType":"pdf","work_url":"https://www.academia.edu/1899421/The_origin_of_the_genetic_code_and_protein_synthesis","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/1899421/The_origin_of_the_genetic_code_and_protein_synthesis"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="1" data-entity-id="69104383" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/69104383/On_the_possible_origin_and_evolution_of_genetic_coding">On the possible origin and evolution of genetic coding</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="67662229" href="https://independent.academia.edu/JacquesDaniel6">Jacques Daniel</a></div><p class="ds-related-work--metadata ds2-5-body-xs">arXiv: Populations and Evolution, 2019</p><p class="ds-related-work--abstract ds2-5-body-sm">To synthesize peptides alongside the RNAs making the so-called RNA world, some genetic coding involving RNA had to develop. Herein, it is proposed that the first real-coding setup was a direct one, made up of continuous poly-tRNA-like molecules, with each tRNA-like moiety carrying, beyond and near its 5 prime or 3 prime end, a trinucleotide site for specific amino acid binding: the sequence and continuity of the tRNA moieties of a particular poly-tRNA would ensure the sequence and continuity of the amino acids of the corresponding peptide or small protein. In parallel with these particular entities, and enhancing their peptide-forming function, a proto-ribosome and primitive amino acid-activation system would develop. At some stage, one critical innovation would be the appearance of RNA fragments that could tighten several adjacent tRNA moieties together on a particular poly-tRNA molecule, by pairing with the second trinucleotide sequence (identical to the first one carrying the spe...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"On the possible origin and evolution of genetic coding","attachmentId":79330304,"attachmentType":"pdf","work_url":"https://www.academia.edu/69104383/On_the_possible_origin_and_evolution_of_genetic_coding","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/69104383/On_the_possible_origin_and_evolution_of_genetic_coding"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="2" data-entity-id="70386581" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/70386581/On_origin_of_genetic_code_and_tRNA_before_translation">On origin of genetic code and tRNA before translation</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="8579705" href="https://elte.academia.edu/EorsSzathmary">Eors Szathmary</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Biology Direct, 2011</p><p class="ds-related-work--abstract ds2-5-body-sm">Background: Synthesis of proteins is based on the genetic code-a nearly universal assignment of codons to amino acids (aas). A major challenge to the understanding of the origins of this assignment is the archetypal "keylock vs. frozen accident" dilemma. Here we reexamine this dilemma in light of 1) the fundamental veto on "foresight evolution", 2) modular structures of tRNAs and aminoacyl-tRNA synthetases, and 3) the updated library of aa-binding sites in RNA aptamers successfully selected in vitro for eight amino acids. Results: The aa-binding sites of arginine, isoleucine and tyrosine contain both their cognate triplets, anticodons and codons. We have noticed that these cases might be associated with palindrome-dinucleotides. For example, one-base shift to the left brings arginine codons CGN, with CG at 1-2 positions, to the respective anticodons NCG, with CG at 2-3 positions. Formally, the concomitant presence of codons and anticodons is also expected in the reverse situation, with codons containing palindrome-dinucleotides at their 2-3 positions, and anticodons exhibiting them at 1-2 positions. A closer analysis reveals that, surprisingly, RNA binding sites for Arg, Ile and Tyr "prefer" (exactly as in the actual genetic code) the anticodon(2-3)/codon(1-2) tetramers to their anticodon(1-2)/ codon(2-3) counterparts, despite the seemingly perfect symmetry of the latter. However, since in vitro selection of aa-specific RNA aptamers apparently had nothing to do with translation, this striking preference provides a new strong support to the notion of the genetic code emerging before translation, in response to catalytic (and possibly other) needs of ancient RNA life. Consistently with the pre-translation origin of the code, we propose here a new model of tRNA origin by the gradual, Fibonacci process-like, elongation of a tRNA molecule from a primordial coding triplet and 5'DCCA3' quadruplet (D is a base-determinator) to the eventual 76 base-long cloverleaf-shaped molecule. Conclusion: Taken together, our findings necessarily imply that primordial tRNAs, tRNA aminoacylating ribozymes, and (later) the translation machinery in general have been co-evolving to ''fit'' the (likely already defined) genetic code, rather than the opposite way around. Coding triplets in this primal pre-translational code were likely similar to the anticodons, with second and third nucleotides being more important than the less specific first one. Later, when the code was expanding in co-evolution with the translation apparatus, the importance of 2-3 nucleotides of coding triplets "transferred" to the 1-2 nucleotides of their complements, thus distinguishing anticodons from codons. This evolutionary primacy of anticodons in genetic coding makes the hypothesis of primal stereo-chemical affinity between amino acids and cognate triplets, the hypothesis of coding coenzyme handles for amino acids, the hypothesis of tRNA-like genomic 3' tags suggesting that tRNAs originated in replication, and the hypothesis of ancient ribozymes-mediated operational code of tRNA aminoacylation not mutually contradicting but rather coexisting in harmony.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"On origin of genetic code and tRNA before translation","attachmentId":80162095,"attachmentType":"pdf","work_url":"https://www.academia.edu/70386581/On_origin_of_genetic_code_and_tRNA_before_translation","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/70386581/On_origin_of_genetic_code_and_tRNA_before_translation"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="3" data-entity-id="70386686" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/70386686/The_origin_of_the_genetic_code_amino_acids_as_cofactors_in_an_RNA_world">The origin of the genetic code: amino acids as cofactors in an RNA world</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="8579705" href="https://elte.academia.edu/EorsSzathmary">Eors Szathmary</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Trends in Genetics, 1999</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"The origin of the genetic code: amino acids as cofactors in an RNA world","attachmentId":80162230,"attachmentType":"pdf","work_url":"https://www.academia.edu/70386686/The_origin_of_the_genetic_code_amino_acids_as_cofactors_in_an_RNA_world","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/70386686/The_origin_of_the_genetic_code_amino_acids_as_cofactors_in_an_RNA_world"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="4" data-entity-id="76685247" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/76685247/On_some_predictions_of_the_poly_tRNA_model_for_the_origin_and_evolution_of_genetic_coding">On some predictions of the poly-tRNA model for the origin and evolution of genetic coding</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="67662229" href="https://independent.academia.edu/JacquesDaniel6">Jacques Daniel</a></div><p class="ds-related-work--metadata ds2-5-body-xs">arXiv: Populations and Evolution, 2020</p><p class="ds-related-work--abstract ds2-5-body-sm">The poly-tRNA model was recently presented for the origin and evolution of genetic coding. This model has led to a rather precise description of what might have occurred at the beginning of protein synthesis in the first life form. Here, we further discuss some interesting implications of this model. First, the system of encoded peptide/protein synthesis appears to have started and developed on the breeding ground of a rich RNA world, responsible for the infancy of life existence and complexity. Furthermore, once protein synthesis was fully established and apparently superseding the RNA world, and at a very early stage of life beginnings, we already see what has been a recurrent theme in the likely interpretation of modern comparative molecular studies on species: the full ability of this nascent life entity to develop itself by tinkering, using all kinds of available pieces to improve itself. Lastly, and very instructively, it is deduced from this model that the first peptides to b...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"On some predictions of the poly-tRNA model for the origin and evolution of genetic coding","attachmentId":84310047,"attachmentType":"pdf","work_url":"https://www.academia.edu/76685247/On_some_predictions_of_the_poly_tRNA_model_for_the_origin_and_evolution_of_genetic_coding","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/76685247/On_some_predictions_of_the_poly_tRNA_model_for_the_origin_and_evolution_of_genetic_coding"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="5" data-entity-id="125412438" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/125412438/Origins_of_Genetic_Coding_Self_Guided_Molecular_Self_Organisation">Origins of Genetic Coding: Self-Guided Molecular Self-Organisation</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="17358809" href="https://auckland.academia.edu/PWills">Peter Wills</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Entropy</p><p class="ds-related-work--abstract ds2-5-body-sm">The origin of genetic coding is characterised as an event of cosmic significance in which quantum mechanical causation was transcended by constructive computation. Computational causation entered the physico-chemical processes of the pre-biotic world by the incidental satisfaction of a condition of reflexivity between polymer sequence information and system elements able to facilitate their own production through translation of that information. This event, which has previously been modelled in the dynamics of Gene–Replication–Translation systems, is properly described as a process of self-guided self-organisation. The spontaneous emergence of a primordial genetic code between two-letter alphabets of nucleotide triplets and amino acids is easily possible, starting with random peptide synthesis that is RNA-sequence-dependent. The evident self-organising mechanism is the simultaneous quasi-species bifurcation of the populations of information-carrying genes and enzymes with aminoacyl-...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Origins of Genetic Coding: Self-Guided Molecular Self-Organisation","attachmentId":119460589,"attachmentType":"pdf","work_url":"https://www.academia.edu/125412438/Origins_of_Genetic_Coding_Self_Guided_Molecular_Self_Organisation","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/125412438/Origins_of_Genetic_Coding_Self_Guided_Molecular_Self_Organisation"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="6" data-entity-id="30577868" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/30577868/Genetic_Code_a_Self_Referential_and_Functional_Model">Genetic Code: a Self-Referential and Functional Model</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="18191518" href="https://cpmtc-igc-ufmg.academia.edu/RomeuGuimaraes">Romeu C Guimaraes</a><span>, </span><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="58214140" href="https://independent.academia.edu/CarlosHenriqueMoreira2">Carlos Henrique Moreira</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Progress in Biological Chirality, 2004</p><p class="ds-related-work--abstract ds2-5-body-sm">A model for construction of the genetic code is presented, based on successive recruitment of pairs of palindromic (bases at the 5´ and 3´ positions are the same in each strand) anticodons. The anticode matrix contains eight pairs of boxes, each box defined by the principal dinucleotide (pDiN; central 3´ base). Triplets may be depicted as •pDiN (•, the 5´ bases). In split boxes, the first occupier amino acid developed four-fold degeneracy then conceded 5´ Y to new attributions, keeping the 5' R. This rule is consistent with the criteria of aminoacyl-tRNA synthetases class 2 (aRS2) preceding aRS1, late entry of specific punctuation, and of amino acids precursor to biosynthesis routes, or originated independently from other amino acids belonging in the code, preceding those derived from precursors. The succession of anticodon pairs is from the homogeneous (Ho) pDiN sector (•RR : •YY quadrants) to the mixed (Mx) sector (•RY : •YR) and from thermodynamically more to less stable pairs. Synthetases formed six couples of the same class in the eight pairs of boxes. In the four-stage scheme, the initial and final ones are composed, respectively, of aRS2-only and aRS1-only boxes, both aRS classes occurring in the pairs of the intermediate stages. Various other correlations indicated the physiologic relevance of the model. Stage 1 is composed by the Ho sector pairs •CC : •GG and •GA : •CU containing, respectively, Gly / Pro and Ser / Ser. It is indicated that early catalysts may not have been of the proteic synthetase type, due to absence of hydropathy correlation in the attributions. Gly may have preceded Pro in the •GG box, due to Pro being derived from Glu, which enters in Stage 2. The three amino acids in this stage contribute strongly to protein N-end stabilization and to RNA-binding motifs, so that a Progress in Biological Chirality 2 stabilized nucleoprotein system could be formed. Stage 2 completes the Ho sector, entering •UC : •AG and •UU : •AA. The central U boxes are initially occupied, respectively, by Asp and Asn. Asp conceded 5' Y to Glu and this with its •AG pair, occupied by Leu, formed an aRS1 couple. Asn conceded 5' Y to Lys, and this plus its •AA pair, occupied by Phe, formed the couple of atypical synthetases: some organisms use LysRS1 instead of class 2; PheRS is class 2 but aminoacylating in the aRS1 fashion, on the 2´ hydroxyl of the terminal adenosine of tRNA. Stage 3 initiates the Mx sector with the pairs •GC : •CG, •UG : •AC and •GU : •CA, containing the last aRS2 attributions together with the abundant entry of aRS1 and of amino acids characteristic of DNA binding motifs. The first and third pairs form couples of synthetases of different classes, AlaRS2 / ArgRS1 and ThrRS2 / CysRS1, TrpRS1. In the second pair, His enters the •UG box and concedes 5´ Y to Gln; this plus its •AC pair, occupied by Val, formed an aRS1 couple. From Thr onward, all amino acids were derived from biosynthesis families and the average amino acid set became more hydrophobic. In Stage 4, the tips of the Mx sector •AU : •UA are occupied by Ile, Met / Tyr and the punctuation signs fMet and X UA . tRNAs corresponding to all stop codons were fished by the initiation system, this with slipped pDiN (fMet CAU instead of Met CAU), generating conflicts solved with deletion of the X tRNAs. The aRS1 hexacodonic expansions were developed, LeuRS and ArgRS receiving, respectively, YAA and YCU. The succession of amino acids indicates that protein secondary structures developed increasing organization: the set characteristic of coils and turns was completed early, then that of helices, lastly the set of strands. In the model of recruitment of tRNA pairs, one of the members of a pair functions as codon to the other. In this way, Stage 1 was entirely self-referential and only coding for protein synthesis, not having been formed for decoding mRNAs. In Stage 2, the linear ordering of codon strings (primitive mRNAs, the first genes) was established, indicating the rise of genetic information: protein-stabilizing amino acids constituted the N-ends, destabilizers added as C-ends. It can be said that genes were defined simultaneously with the definition of products, at the moment of the binding of RNAs and proteins, in the process of formation of the coding system.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Genetic Code: a Self-Referential and Functional Model","attachmentId":51019563,"attachmentType":"pdf","work_url":"https://www.academia.edu/30577868/Genetic_Code_a_Self_Referential_and_Functional_Model","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/30577868/Genetic_Code_a_Self_Referential_and_Functional_Model"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="7" data-entity-id="31352495" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/31352495/Experimental_studies_on_the_origin_of_the_genetic_code_and_the_process_of_protein_synthesis_A_review_update">Experimental studies on the origin of the genetic code and the process of protein synthesis: A review update</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="59820685" href="https://independent.academia.edu/NalinieWickramasinghe">Nalinie Wickramasinghe</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Origins of Life and Evolution of the Biosphere, 1992</p><p class="ds-related-work--abstract ds2-5-body-sm">This article is an update of our earlier review in this journal on the origin of the genetic code and the process of protein synthesis. It is our intent to discuss only experimental evidence published since then although there is the necessity to mention the old enough to place the new in context. We do not include theoretical nor hypothetical treatments of the code or protein synthesis. Relevant data regarding the evolution of tRNAs and the recognition of tRNAs by aminoacyt-tRNA-synthetases are discussed. Our present belief is that the code arose based on a core of early assignments which were made on a physico-chemical and anticodonic basis and this was expanded with new assignments later. These late assignments do not necessarily show an amino acidanticodon relatedness. In spite of the fact that most data suggest a code origin based on amino acidanticodon relationships, some new data suggesting preferential binding of Arg to its codons are discussed. While information regarding coding is not increasing very rapidly, information regarding the basic chemistry of the process of protein synthesis has increased significantly, principally relating to aminoacylation of mono-and polyribonucleotides. Included in those studies are several which show stereoselective reactions of L-amino acids with nucleotides having D-sugars. Hydrophobic interactions definitely play a role in the preferences which have been observed.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Experimental studies on the origin of the genetic code and the process of protein synthesis: A review update","attachmentId":51734026,"attachmentType":"pdf","work_url":"https://www.academia.edu/31352495/Experimental_studies_on_the_origin_of_the_genetic_code_and_the_process_of_protein_synthesis_A_review_update","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/31352495/Experimental_studies_on_the_origin_of_the_genetic_code_and_the_process_of_protein_synthesis_A_review_update"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="8" data-entity-id="54597635" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/54597635/Interdependence_Reflexivity_Fidelity_Impedance_Matching_And_The_Evolution_Of_Genetic_Coding">Interdependence, Reflexivity, Fidelity, Impedance Matching, And The Evolution Of Genetic Coding</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="23452151" href="https://unc.academia.edu/CharlesCarter">Charles Carter</a></div><p class="ds-related-work--abstract ds2-5-body-sm">Genetic coding is generally thought to have required ribozymes whose functions were taken over by polypeptide aminoacyl-tRNA synthetases (aaRS). Two discoveries about aaRS and their tRNA substrates now furnish a unifying rationale for the opposite conclusion: that the key processes of the Central Dogma of molecular biology emerged simultaneously and naturally from simple origins in a peptide·RNA partnership, eliminating the epistemological need for a prior RNA world. First, the two aaRS classes likely arose from opposite strands of the same ancestral gene, implying a simple genetic alphabet. Inversion symmetries in aaRS structural biology arising from genetic complementarity would have stabilized the initial and subsequent differentiation of coding specificities and hence rapidly promoted diversity in the proteome. Second, amino acid physical chemistry maps onto tRNA identity elements, establishing reflexivity in protein aaRS. Bootstrapping of increasingly detailed coding is thus in...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Interdependence, Reflexivity, Fidelity, Impedance Matching, And The Evolution Of Genetic Coding","attachmentId":70886465,"attachmentType":"pdf","work_url":"https://www.academia.edu/54597635/Interdependence_Reflexivity_Fidelity_Impedance_Matching_And_The_Evolution_Of_Genetic_Coding","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/54597635/Interdependence_Reflexivity_Fidelity_Impedance_Matching_And_The_Evolution_Of_Genetic_Coding"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="9" data-entity-id="60078349" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/60078349/The_transition_from_noncoded_to_coded_protein_synthesis_did_coding_mRNAs_arise_from_stability_enhancing_binding_partners_to_tRNA">The transition from noncoded to coded protein synthesis: did coding mRNAs arise from stability-enhancing binding partners to tRNA?</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="51877686" href="https://independent.academia.edu/StephenBernhardt">Stephen Bernhardt</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Biology Direct, 2010</p><p class="ds-related-work--abstract ds2-5-body-sm">Background: Understanding the origin of protein synthesis has been notoriously difficult. We have taken as a starting premise Wolf and Koonin's view that "evolution of the translation system is envisaged to occur in a compartmentalized ensemble of replicating, co-selected RNA segments, i.e., in an RNA world containing ribozymes with versatile activities". Presentation of the hypothesis: We propose that coded protein synthesis arose from a noncoded process in an RNA world as a natural consequence of the accumulation of a range of early tRNAs and their serendipitous RNA binding partners. We propose that, initially, RNA molecules with 3' CCA termini that could be aminoacylated by ribozymes, together with an ancestral peptidyl transferase ribozyme, produced small peptides with random or repetitive sequences. Our concept is that the first tRNA arose in this context from the ligation of two RNA hairpins and could be similarly aminoacylated at its 3' end to become a substrate for peptidyl transfer catalyzed by the ancestral ribozyme. Within this RNA world we hypothesize that proto-mRNAs appeared first simply as serendipitous binding partners, forming complementary base pair interactions with the anticodon loops of tRNA pairs. Initially this may have enhanced stability of the paired tRNA molecules so they were held together in close proximity, better positioning the 3' CCA termini for peptidyl transfer and enhancing the rate of peptide synthesis. If there were a selective advantage for the ensemble through the peptide products synthesized, it would provide a natural pathway for the evolution of a coding system with the expansion of a cohort of different tRNAs and their binding partners. The whole process could have occurred quite unremarkably for such a profound acquisition. Testing the hypothesis: It should be possible to test the different parts of our model using the isolated contemporary 50S ribosomal subunit initially, and then with RNAs transcribed in vitro together with a minimal set of ribosomal proteins that are required today to support protein synthesis. Implications of the hypothesis: This model proposes that genetic coding arose de novo from complementary base pair interactions between tRNAs and single-stranded RNAs present in the immediate environment. Reviewers: This article was reviewed by Eugene Koonin, Rob Knight and Berthold Kastner (nominated by Laura Landweber).</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"The transition from noncoded to coded protein synthesis: did coding mRNAs arise from stability-enhancing binding partners to tRNA?","attachmentId":73679127,"attachmentType":"pdf","work_url":"https://www.academia.edu/60078349/The_transition_from_noncoded_to_coded_protein_synthesis_did_coding_mRNAs_arise_from_stability_enhancing_binding_partners_to_tRNA","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/60078349/The_transition_from_noncoded_to_coded_protein_synthesis_did_coding_mRNAs_arise_from_stability_enhancing_binding_partners_to_tRNA"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div></div></div><div class="ds-sticky-ctas--wrapper js-loswp-sticky-ctas hidden"><div class="ds-sticky-ctas--grid-container"><div class="ds-sticky-ctas--container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--sticky-ctas","attachmentId":72866911,"attachmentType":"pdf","workUrl":null}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--sticky-ctas","attachmentId":72866911,"attachmentType":"pdf","workUrl":null}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div></div><div class="ds-below-fold--grid-container"><div class="ds-work--container js-loswp-embedded-document"><div class="attachment_preview" data-attachment="Attachment_72866911" style="display: none"><div class="js-scribd-document-container"><div class="scribd--document-loading js-scribd-document-loader" style="display: block;"><img alt="Loading..." src="//a.academia-assets.com/images/loaders/paper-load.gif" /><p>Loading Preview</p></div></div><div style="text-align: center;"><div class="scribd--no-preview-alert js-preview-unavailable"><p>Sorry, preview is currently unavailable. 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