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Did DNA replication evolve twice independently?
Open accessAbstract
DNA replication is central to all extant cellular organisms. There are substantial functional similarities between the bacterial and the archaeal/eukaryotic replication machineries, including but not limited to defined origins, replication bidirectionality, RNA primers and leading and lagging strand synthesis. However, several core components of the bacterial replication machinery are unrelated or only distantly related to the functionally equivalent components of the archaeal/eukaryotic replication apparatus. This is in sharp contrast to the principal proteins involved in transcription and translation, which are highly conserved in all divisions of life. We performed detailed sequence comparisons of the proteins that fulfill indispensable functions in DNA replication and classified them into four main categories with respect to the conservation in bacteria and archaea/eukaryotes: (i) non-homologous, such as replicative polymerases and primases; (ii) containing homologous domains but apparently non-orthologous and conceivably independently recruited to function in replication, such as the principal replicative helicases or proofreading exonucleases; (iii) apparently orthologous but poorly conserved, such as the sliding clamp proteins or DNA ligases; (iv) orthologous and highly conserved, such as clamp-loader ATPases or 5'-->3' exonucleases (FLAP nucleases). The universal conservation of some components of the DNA replication machinery and enzymes for DNA precursor biosynthesis but not the principal DNA polymerases suggests that the last common ancestor (LCA) of all modern cellular life forms possessed DNA but did not replicate it the way extant cells do. We propose that the LCA had a genetic system that contained both RNA and DNA, with the latter being produced by reverse transcription. Consequently, the modern-type system for double-stranded DNA replication likely evolved independently in the bacterial and archaeal/eukaryotic lineages.
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“Specifically, the last common ancestor may have had a cell membrane (Jékely 2006;Koga 2011;Lombard et al. 2012;Sojo et al. 2014;Coleman et al. 2019), RNA and phosphodiester-based energy coupling (e.g.Werner and Grohmann 2011), as well as thioester-based intermediary metabolism (Goldford et al. 2017;Weiss et al. 2018), but may not have used a strictly DNA genome (Mushegian and Koonin 1996;Leipe et”
From The Emergence of Life (2019) · cites this paper as Leipe et al. 1999
In the citing paper
“The fact that the mechanisms of DNA replication in bacteria and archaea are different [133] suggests the possibility that DNA, as the primary information storage molecule, evolved independently in each of these lineages [133,134,135].”
From Opinion: The Key Steps in the Origin of Life to the Formation of the Eukaryotic Cell (2024) · cites this paper as [134]
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BackgroundSelf-citation
Metadata
- Authors
- Leipe, D. D., Aravind, L., & Koonin, E. V.
- Affiliations
- National Institutes of Health (US)
- Texas A&M University (US)
- Corresponding author
- Koonin, E. V.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 1999-09-01
- Volume
- 27
- Issue
- 17
- Pages
- 3389-3401
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC148579
- OpenAlex
- W2018024025
- Semantic Scholar
- 9f9be31d2a06621cfbcaa7642db469b8cea929dc
- Cited by
- 351
- References
- 66
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 16 · 2023: 5 · 2022: 5 · 2021: 11 · 2020: 10 · 2019: 6 · 2018: 12 · 2017: 13 · 2016: 15 · 2015: 13 · 2014: 18 · 2013: 12 · 2012: 5
- FWCI
- 13.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nucleic Acids Research (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Physics and Astronomy › Astronomy and Astrophysics › Origins and Evolution of Life
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- DNA replication, origin of replication, convergent evolution, last common ancestor, primase, replicative helicase, proofreading exonuclease, DNA ligase, RNA-DNA hybrids, reverse transcription, sequence conservation
- MeSH terms
- Animals, Bacterial Proteins, Cytoplasm, DNA Replication, Drosophila, Fungal Proteins, Models, Genetic, Sequence Homology, Nucleic Acid, Databases, Factual, Sequence Analysis, DNA, Evolution, Molecular, Archaeal Proteins
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