The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index.
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Citations
Cites
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs
Altschul, S. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.17.3389 · Cited by 73,302
A genomic perspective on protein families.
Tatusov, R., Koonin, E., & Lipman, D. (1997) · Science · doi:10.1126/science.278.5338.631 · Cited by 3,777
Self-citationCrystal structure at 3.5 A resolution of HIV-1 reverse transcriptase complexed with an inhibitor
Kohlstaedt, L. A., Wang, J., Friedman, J. M., Rice, P. A., & Steitz, T. A. (1992) · Science · doi:10.1126/science.1377403 · Cited by 1,914
Neuwald, A. F., Aravind, L., Spouge, J. L., & Koonin, E. V. (1999) · Genome Research · doi:10.1101/gr.9.1.27 · Cited by 1,840
Self-citationHelicases: amino acid sequence comparisons and structure-function relationships
Gorbalenya, A. E., & Koonin, E. V. (1993) · Current Opinion in Structural Biology · doi:10.1016/s0959-440x(05)80116-2 · Cited by 1,160
Self-citationWoese, C. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.12.6854 · Cited by 1,053
Conservation of gene order: a fingerprint of proteins that physically interact
Dandekar, T. (1998) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(98)01274-2 · Cited by 1,047
An atypical topoisomerase II from archaea with implications for meiotic recombination
Bergerat, A., de Massy, B., Gadelle, D., Varoutas, P.-C., Nicolas, A. G., & Forterre, P. (1997) · Nature · doi:10.1038/386414a0 · Cited by 948
Murzin, A. G. (1993) · The EMBO Journal · doi:10.1002/j.1460-2075.1993.tb05726.x · Cited by 929
A minimal gene set for cellular life derived by comparison of complete bacterial genomes
Mushegian, A. R., & Koonin, E. V. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.19.10268 · Cited by 916
Self-citation
Research works printed but not linked: 2
- 1997, ISMB, 5, 333
- 1997, Biokhimii a (Moscow, Russia), 62, 1202
Cited by
Sorted by citations
Items 301–351 of 351
A structural snapshot of the multiple working states of the Mpox virus helicase–primase D5
Guo, Y., & Yan, R. (2024) · FEBS Journal · doi:10.1111/febs.17292 · Cited by 1
“Despite foundational similarities in replication mechanisms across eukaryotes, prokaryotes, archaea, and viruses, signifi-cant divergences exist [10].”
Rudd, S. R., Miranda, L. S., Asariah, S., Rodgers, C. S., Estrada, J. T., Alonzo, M. A., & Bideshi, D. K. (2025) · Pathogens · doi:10.3390/pathogens14111094 · Cited by 1
“AVs replicate their DNA using B family polymerases similar to eukaryotic α , δ , and ε polymerases, featuring proofreading exonucle-ase domains [194,195].”
Hunker, O., & Bleichert, F. (2025) · The EMBO Journal · doi:10.1038/s44318-025-00628-5 · Cited by 1
“All eukaryotes possess replication machineries with an evolutionary lineage that can be traced to Archaea (Leipe et al, 1999; Makarova and Koonin, 2013).”
DNA polymerase I: structure, activity, and function in bacterial DNA replication and repair
Lowder, F. C., & Simmons, L. A. (2026) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2026.2682122 · Cited by 1
DNA, Gene Structure, and DNA Replication
Hoy, M. A. (2003) · Elsevier eBooks · doi:10.1016/b978-012357031-4/50020-0 · Cited by 1
King, C. C. (2011) · DNA Decipher Journal · Cited by 1
LUCA – letzter gemeinsamer Vorfahre allen Lebens
Mulkidjanian, A. Y., & Lankenau, D. (2011) · Wiley eBooks · doi:10.1002/9783527653935.ch7
Koonin, E. V. (2007) · arXiv (Cornell University) · doi:10.48550/arxiv.q-bio/0701023 · Cited by 1
“membrane biogenesis, are highly diverged or even non-homologous in bacteria and archaea, the two primary kingdoms of prokaryotes [6-10].”
Self-citationDuffy, C. M. (2016) · The Journal of the American Medical Association (JAMA) Network (American Medical Association) · doi:10.13028/m22p45 · Cited by 1
“Despite low sequence conservation, the general architecture of sliding clamps is highly conserved throughout all domains of life (5, 49, 50).”
BackgroundExtremophiles and Horizontal Gene Transfer: Clues to the Emergence of Life
Jheeta, S. (2020) · Wiley eBooks · doi:10.1002/9781119593096.ch16 · Cited by 1
Smith, S. J., Li, C. M., Hickey, R. J., & Malkas, L. H. (2014) · Wiley eBooks · doi:10.1002/9780470015902.a0001041.pub3 · Cited by 1
Last Universal Common Ancestor
Delaye, L. (2023) · Encyclopedia of Astrobiology · doi:10.1007/978-3-662-65093-6_1728 · Cited by 1
Egel, R. (2024) · Preprints.org · doi:10.20944/preprints202405.0555.v1
Eme, L. (2011) · theses.fr (ABES) · doi:10.70675/f6a87363z8acaz4487z93e0z57bc870cf584 · Cited by 1
Vesteg, M., & Krajčovič, J. (2010) · Cellular origin and life in extreme habitats · doi:10.1007/978-90-481-9449-0_4 · Cited by 1
How the endosymbiont got its cell
Poole, A. M. (2024) · New Zealand Science Review · doi:10.26686/nzsr.v66.9440
“In particular, archaeal and eukaryotic DNA replication and transcription machineries share greater similarity to one another than either does to bacteria (Edgell & Doolittle 1997; Forterre et al. 2004; Leipe et al. 1999; Cramer 2002).”
BackgroundSnider, B. M., Phipps, E. A., Smith, S. J., et al. (2009) · Encyclopedia of Life Sciences · doi:10.1002/9780470015902.a0001041.pub2
An Optimized Distance Function for Comparison of Protein Binding Sites
Iván, G. (2007) · Springer eBooks · doi:10.1007/978-3-540-73731-5_9
Jordan, I. K., & Koonin, E. V. (2008) · Wiley eBooks · doi:10.1002/9780470015902.a0005296.pub2
Self-citationViral Origins of Telomeres and Telomerases
Witzany, G. (2009) · Springer eBooks · doi:10.1007/978-90-481-3319-2_9
Cell Cycle Analysis of Archaea
Poplawski, A. B. (2000) · KTH Publication Database DiVA (KTH Royal Institute of Technology)
Comparative genomics and early cell evolution
Lazcano, A. (2011) · Cambridge University Press eBooks · doi:10.1017/cbo9780511933875.019
“…topoisomerases, gyrases and 5′-3′ exonucleases) across the entire phylogenetic spectrum (Olsen and Woese, 1997 ; Edgell and Doolittle, 1997 ; Leipe et al ., 1999 ; Penny and Poole, 1999 ), comparative proteome analysis has shown that (eu)bacterial replicative polymerases and primases lack…”
Luca : à la recherche du plus proche ancêtre commun
Gribaldo, S. (2005)
SURVEY AND SUMMARY Darwinian evolution in the light of genomics
Koonin, E. V. (2009)
Self-citationREPLICATIVE DNA POLYMERASE ASSOCIATED B-SUBUNITS
Oulu, B. (2004)
Replicative DNA polymerase associated B-subunits
Jokela, M. (2004)
Optical tweezers reveal how proteins alter replication
Chaurasiya, K. R. (2013) · doi:10.17760/d20003102
[Studies on DNA replication mechanism and related proteins in Archaea].
Ishino, Y. (2001) · Nippon Saikingaku Zasshi · doi:10.3412/jsb.56.435
Prebiological Organization of Molecules in Models and in the Matter of the Origin of Life
Zhogol, R. A., & . (2018) · International Journal of Engineering & Technology · doi:10.14419/ijet.v7i3.14.17044
“A comparison of bacterial and archaeal enzymes reveals the least similarity in the most important components of replication-DNAdependent-DNA polymerase and primase (Leipe et al., 1999).”
BackgroundThe Origin(s) of Cell: Some Radical New HypothesesPreprint
Tang, S. (2020) · Preprints.org · doi:10.20944/preprints202002.0039.v1
“The possibility that streamlining or simplification via loss of functions and genes came after the divergence of bacteria and Archaea from LUCA goes against the thesis that the FUCA or LUCA was a proto-eukaryotic cell, and bacteria, Archaea, and Eukaryotes came to exist via genetic reduction or loss of function in pro…”
BackgroundInfluentialLast Universal Common Ancestor
Delaye, L. (2015) · Encyclopedia of Astrobiology · doi:10.1007/978-3-662-44185-5_1728
DNA, Gene Structure, and DNA Replication
Hoy, M. A. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-415874-0.00001-9 · Cited by 1
Ewolucjonizm darwinowski w świetle genomiki
Koonin, E. V. (2021) · Filozoficzne Aspekty Genezy · doi:10.53763/fag.2018.15.154
Self-citation(2006) · Archaea · doi:10.1002/9780470750865.refs
Extremophiles and Extreme Environments
Rampelotto, P. H. (2016) · MDPI eBooks · doi:10.3390/books978-3-03842-178-8
Griep, M. A., & Periago, J. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-809633-8.06950-8
Last Universal Common Ancestor
Delaye, L. (2014) · Encyclopedia of Astrobiology · doi:10.1007/978-3-642-27833-4_1728-4
(2007) · Elsevier eBooks · doi:10.1016/b978-012088794-1/50015-x
Comparison of Bacterial and Eukaryotic Replisome Components
Yao, N. Y., & O’Donnell, M. E. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-821618-7.00097-3
Lynch, M. (2024) · Oxford University Press eBooks · doi:10.1093/oso/9780192847287.003.0003
Lynch, M. (2024) · Oxford University Press eBooks · doi:10.1093/oso/9780192847287.003.0002
Liu, B., Yan, J., Guo, Z., Chen, X., & Zhang, Z. (2024) · Current Cancer Drug Targets · doi:10.2174/0115680096300546240530071830
The Cell as a Complex System and the S-Space Axiomatic Wave Model Adequacy Checking
(2024) · Advances in religious and cultural studies (ARCS) book series · doi:10.4018/978-1-6684-8509-5.ch002
A stoichiometric selection advantage of DNA genomes over RNA genomesPreprint
Yu, R. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.22.683889
Étude de l’origine des eucaryotes par la phylogénie moléculaire
de Lempdes, N. R. (2014) · theses.fr (ABES) · doi:10.70675/76910e99z19a8z4804z8037z63f214c6e5a9
Phylogenomic study of the evolutionary history of the Archaea and their link with eukaryogenesis
Aouad, M. (2018) · theses.fr (ABES) · doi:10.70675/f9fbb237z6ebfz42f5zb132zaed46e39783a
Broecker, F. (2026) · Springer eBooks · doi:10.1007/978-3-032-24295-2_10 · Cited by 1
Structural basis of the nucleotide incorporation cycle of bacterial DNA polymerase IIIPreprint
Xu, Z., Jergic, S., Zhu, Q., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.29.735100
Musat, F., Wöhlbrand, L., Jarling, R., et al. (2026) · Environmental Microbiology · doi:10.1111/1462-2920.70394
Assembly and Mechanism of Action of Sulfolobus solfataricus DNA Replication Complexes
Bauer, R. J. (2014) · D-Scholarship@Pitt (University of Pittsburgh)
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
