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