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      Stochastic Emergence of Two Distinct Self-Replicators from a Dynamic Combinatorial Library

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          Abstract

          Unraveling how chemistry can give rise to biology is one of the greatest challenges of contemporary science. Achieving life-like properties in chemical systems is therefore a popular topic of research. Synthetic chemical systems are usually deterministic: the outcome is determined by the experimental conditions. In contrast, many phenomena that occur in nature are not deterministic but caused by random fluctuations (stochastic). Here, we report on how, from a mixture of two synthetic molecules, two different self-replicators emerge in a stochastic fashion. Under the same experimental conditions, the two self-replicators are formed in various ratios over several repeats of the experiment. We show that this variation is caused by a stochastic nucleation process and that this stochasticity is more pronounced close to a phase boundary. While stochastic nucleation processes are common in crystal growth and chiral symmetry breaking, it is unprecedented for systems of synthetic self-replicators.

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          Most cited references36

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          Supramolecular polymerization.

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            Noise in protein expression scales with natural protein abundance.

            Noise in gene expression is generated at multiple levels, such as transcription and translation, chromatin remodeling and pathway-specific regulation. Studies of individual promoters have suggested different dominating noise sources, raising the question of whether a general trend exists across a large number of genes and conditions. We examined the variation in the expression levels of 43 Saccharomyces cerevisiae proteins, in cells grown under 11 experimental conditions. For all classes of genes and under all conditions, the expression variance was approximately proportional to the mean; the same scaling was observed at steady state and during the transient responses to the perturbations. Theoretical analysis suggests that this scaling behavior reflects variability in mRNA copy number, resulting from random 'birth and death' of mRNA molecules or from promoter fluctuations. Deviation of coexpressed genes from this general trend, including high noise in stress-related genes and low noise in proteasomal genes, may indicate fluctuations in pathway-specific regulators or a differential activation pattern of the underlying gene promoters.
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              A self-replicating peptide.

              The production of amino acids and their condensation to polypeptides under plausibly prebiotic conditions have long been known. But despite the central importance of molecular self-replication in the origin of life, the feasibility of peptide self-replication has not been established experimentally. Here we report an example of a self-replicating peptide. We show that a 32-residue alpha-helical peptide based on the leucine-zipper domain of the yeast transcription factor GCN4 can act autocatalytically in templating its own synthesis by accelerating the thioester-promoted amide-bond condensation of 15- and 17-residue fragments in neutral, dilute aqueous solutions. The self-replication process displays parabolic growth pattern with the initial rates of product formation correlating with the square-foot of initial template concentration.
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                Author and article information

                Journal
                J Am Chem Soc
                J Am Chem Soc
                ja
                jacsat
                Journal of the American Chemical Society
                American Chemical Society
                0002-7863
                1520-5126
                31 March 2022
                13 April 2022
                : 144
                : 14
                : 6291-6297
                Affiliations
                []Centre for Systems Chemistry, Stratingh Institute, University of Groningen , Nijenborgh 4, 9747 AG Groningen, The Netherlands
                []Groningen Biomolecular Sciences and Biotechnology Institute & Zernike Institute for Advanced Materials, University of Groningen , Groningen 9747 AG, The Netherlands
                Author notes
                Author information
                https://orcid.org/0000-0001-6388-0461
                https://orcid.org/0000-0001-9875-2320
                https://orcid.org/0000-0001-9273-4850
                https://orcid.org/0000-0002-6892-5611
                https://orcid.org/0000-0003-0259-5637
                Article
                10.1021/jacs.1c12591
                9011346
                35357150
                5c677b9a-6381-4be4-953a-a876e3b43a35
                © 2022 The Authors. Published by American Chemical Society

                Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 30 November 2021
                Funding
                Funded by: H2020 European Research Council, doi 10.13039/100010663;
                Award ID: 741774
                Funded by: China Scholarship Council, doi 10.13039/501100004543;
                Award ID: NA
                Funded by: Ministerie van Onderwijs, Cultuur en Wetenschap, doi 10.13039/501100003245;
                Award ID: 024.001.035
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                ja1c12591
                ja1c12591

                Chemistry
                Chemistry

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