eprintid: 10153099 rev_number: 7 eprint_status: archive userid: 699 dir: disk0/10/15/30/99 datestamp: 2022-08-03 15:32:22 lastmod: 2022-08-03 15:32:22 status_changed: 2022-08-03 15:32:22 type: article metadata_visibility: show sword_depositor: 699 creators_name: Harrison, Stuart A creators_name: Palmeira, Raquel Nunes creators_name: Halpern, Aaron creators_name: Lane, Nick title: A biophysical basis for the emergence of the genetic code in protocells ispublished: inpress divisions: C08 divisions: F99 divisions: B02 divisions: UCL divisions: D09 keywords: Autotrophy, Genetic code, Origin of life, Protocells note: This is an Open Access article published under a Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). abstract: The origin of the genetic code is an abiding mystery in biology. Hints of a 'code within the codons' suggest biophysical interactions, but these patterns have resisted interpretation. Here, we present a new framework, grounded in the autotrophic growth of protocells from CO2 and H2. Recent work suggests that the universal core of metabolism recapitulates a thermodynamically favoured protometabolism right up to nucleotide synthesis. Considering the genetic code in relation to an extended protometabolism allows us to predict most codon assignments. We show that the first letter of the codon corresponds to the distance from CO2 fixation, with amino acids encoded by the purines (G followed by A) being closest to CO2 fixation. These associations suggest a purine-rich early metabolism with a restricted pool of amino acids. The second position of the anticodon corresponds to the hydrophobicity of the amino acid encoded. We combine multiple measures of hydrophobicity to show that this correlation holds strongly for early amino acids but is weaker for later species. Finally, we demonstrate that redundancy at the third position is not randomly distributed around the code: non-redundant amino acids can be assigned based on size, specifically length. We attribute this to additional stereochemical interactions at the anticodon. These rules imply an iterative expansion of the genetic code over time with codon assignments depending on both distance from CO2 and biophysical interactions between nucleotide sequences and amino acids. In this way the earliest RNA polymers could produce non-random peptide sequences with selectable functions in autotrophic protocells. date: 2022-07-19 date_type: published publisher: Elsevier BV official_url: https://doi.org/10.1016/j.bbabio.2022.148597 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1967702 doi: 10.1016/j.bbabio.2022.148597 medium: Print-Electronic pii: S0005-2728(22)00066-4 lyricists_name: Lane, Nicholas lyricists_id: NJLAN31 actors_name: Kalinowski, Damian actors_id: DKALI47 actors_role: owner funding_acknowledgements: 2236041 [NERC]; BB/V003542/1 [Biotechnology and Biological Sciences Research Council] full_text_status: public publication: Biochimica et Biophysica Acta (BBA) - Bioenergetics article_number: 148597 event_location: Netherlands issn: 0005-2728 citation: Harrison, Stuart A; Palmeira, Raquel Nunes; Halpern, Aaron; Lane, Nick; (2022) A biophysical basis for the emergence of the genetic code in protocells. Biochimica et Biophysica Acta (BBA) - Bioenergetics , Article 148597. 10.1016/j.bbabio.2022.148597 <https://doi.org/10.1016/j.bbabio.2022.148597>. (In press). Green open access document_url: https://discovery-pp.ucl.ac.uk/id/eprint/10153099/1/Lane_A%20biophysical%20basis%20for%20the%20emergence%20of%20the%20genetic%20code%20in%20protocells_Pre-proof.pdf