Halpern, Aaron;
(2024)
The origin of genetic coding and translation in protocells.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
The origin of the genetic code is a longstanding problem at the centre of biology. The code is the essential informational framework through which cells are able to self-replicate and evolve, but the process in which it emerged is unknown. One through-line in the literature is that the code may be an emergent property of the biochemistry of amino acid polymerization, but this is rarely stated explicitly. This thesis explores the chemistry of translation and investigates the idea that the polymerization mechanisms used by biology could occur spontaneously in mixtures of amino acids and nucleotides. The focus of this is the centrality of adenine nucleotides in translation. Initially, I utilise molecular dynamics simulations to explore the formation of ATP, a key reactant in translation, and link these results to prior laboratory studies. Using the same pipeline developed for these simulations, I find that adenine nucleotides readily self-organise in ways that should predispose the key chemical steps preceding amino acid polymerization to occur. However, the reason for adenine nucleotides’ universality in this process remains unclear and may either be related to their proclivity of to form triphosphates, or other chemical properties related to reactivity. Similar investigative approaches are then turned towards biological information. Through literature review, extensive molecular dynamics simulations and NMR, I present evidence that fundamental biophysical properties of amino acids and nucleotides can bias their interactions in ways which reproduce the patterns and structure of the modern genetic code. These patterns are principally related to hydrophobicity, which is identified as a significant factor for interactions, and elevated affinities for cognate anticodonic nucleotides. Overall, this thesis describes how spontaneous reactions and interactions may have provided sufficient foundations for the genetic code, foundations which were then augmented by the evolution of the biological translational machinery but never fully replaced.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | The origin of genetic coding and translation in protocells |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | This version is the version of record. For information on re-use, please Copyright © The Author 2024. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. refer to the publisher’s terms and conditions. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > MAPS Faculty Office |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10187560 |
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