Darwinian Evolution of Self-Replicating DNA in a Synthetic Protocell.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
22 Oct 2024
22 Oct 2024
Historique:
received:
30
04
2024
accepted:
03
10
2024
medline:
22
10
2024
pubmed:
22
10
2024
entrez:
21
10
2024
Statut:
epublish
Résumé
Replication, heredity, and evolution are characteristic of Life. We and others have postulated that the reconstruction of a synthetic living system in the laboratory will be contingent on the development of a genetic self-replicator capable of undergoing Darwinian evolution. Although DNA-based life dominates, the in vitro reconstitution of an evolving DNA self-replicator has remained challenging. We hereby emulate in liposome compartments the principles according to which life propagates information and evolves. Using two different experimental configurations supporting intermittent or semi-continuous evolution (i.e., with or without DNA extraction, PCR, and re-encapsulation), we demonstrate sustainable replication of a linear DNA template - encoding the DNA polymerase and terminal protein from the Phi29 bacteriophage - expressed in the 'protein synthesis using recombinant elements' (PURE) system. The self-replicator can survive across multiple rounds of replication-coupled transcription-translation reactions in liposomes and, within only ten evolution rounds, accumulates mutations conferring a selection advantage. Combined data from next-generation sequencing with reverse engineering of some of the enriched mutations reveal nontrivial and context-dependent effects of the introduced mutations. The present results are foundational to build up genetic complexity in an evolving synthetic cell, as well as to study evolutionary processes in a minimal cell-free system.
Identifiants
pubmed: 39433731
doi: 10.1038/s41467-024-53226-0
pii: 10.1038/s41467-024-53226-0
doi:
Substances chimiques
Liposomes
0
DNA
9007-49-2
DNA-Directed DNA Polymerase
EC 2.7.7.7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
9091Subventions
Organisme : Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)
ID : BaSyC 024.003.019
Organisme : Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)
ID : NanoFront
Organisme : Agence Nationale de la Recherche (French National Research Agency)
ID : ANR-22-CPJ2-0091-01
Organisme : EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 Marie Skłodowska-Curie Actions (H2020 Excellent Science - Marie Skłodowska-Curie Actions)
ID : 707404
Informations de copyright
© 2024. The Author(s).
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