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Unusual biology across a group comprising more than 15% of domain Bacteria
Open accessAbstract
A prominent feature of the bacterial domain is a radiation of major lineages that are defined as candidate phyla because they lack isolated representatives. Bacteria from these phyla occur in diverse environments and are thought to mediate carbon and hydrogen cycles. Genomic analyses of a few representatives suggested that metabolic limitations have prevented their cultivation. Here we reconstructed 8 complete and 789 draft genomes from bacteria representing >35 phyla and documented features that consistently distinguish these organisms from other bacteria. We infer that this group, which may comprise >15% of the bacterial domain, has shared evolutionary history, and describe it as the candidate phyla radiation (CPR). All CPR genomes are small and most lack numerous biosynthetic pathways. Owing to divergent 16S ribosomal RNA (rRNA) gene sequences, 50-100% of organisms sampled from specific phyla would evade detection in typical cultivation-independent surveys. CPR organisms often have self-splicing introns and proteins encoded within their rRNA genes, a feature rarely reported in bacteria. Furthermore, they have unusual ribosome compositions. All are missing a ribosomal protein often absent in symbionts, and specific lineages are missing ribosomal proteins and biogenesis factors considered universal in bacteria. This implies different ribosome structures and biogenesis mechanisms, and underlines unusual biology across a large part of the bacterial domain.
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“Trees visualized at https://itol.embl.de/itol.cgiusing Netwick files from Hug et al. (2016) concatenated ribosomal proteins in place of 16S rRNA genes (Fig. 3B) indicate that a large radiation of predominantly uncultured mesophilic taxa, which are comprised of potentially symbiotic organisms with small cells and genomes and are referred to as the bacterial candidate phyla radiation (CPR) and the”
From The Emergence of Life (2019) · cites this paper as Brown et al. 2015
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“Other studies have reported 241 success enriching ultra-small microbes this way (1, 26, 28).”
BackgroundMethodResultInfluentialSelf-citationCornish, K. A. S., Lange, J., Aevarsson, A., & Pohl, E. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.101919 · Cited by 10
“As these sequences are the key for uncovering new species by PCR techniques, it is estimated that at least half of the organisms sampled from the CPR would remain undetected in typical PCR surveys (10).”
BackgroundFuster, M., Billard, H., Bronner, G., Sime-Ngando, T., & Colombet, J. (2022) · Microbial Ecology · doi:10.1007/s00248-022-01974-1 · Cited by 3
“Attempts to evaluate the quantitative and qualitative importance of CPR/DPANN [11, 12], BMOPs [13], and EVs [14] underscore this necessity.”
BackgroundRates of primary production in groundwater rival those in oligotrophic marine systems
Overholt, W., Trumbore, S., Xu, X.-M., Bornemann, T., Probst, A., Krüger, M., Herrmann, M., Thamdrup, B., Bristow, L., Taubert, M., et al. (2021) · bioRxiv · doi:10.1101/2021.10.13.464073 · Cited by 3
Whaley-Martin, K., Chen, L.-X., Nelson, T., Gordon, J., Kantor, R. S., Twible, L. E., Marshall, S., Rossi, L., Bessette, B., Baron, C., et al. (2021) · bioRxiv · doi:10.1101/2021.09.16.460096 · Cited by 3
Self-citationDelwiche, C. F. (2021) · Current Biology · doi:10.1016/j.cub.2021.05.059 · Cited by 2
Jaffe, A. L., He, C., Keren, R., Valentin-Alvarado, L., Munk, P., Bouma-Gregson, K., Farag, I. F., Amano, Y., Sachdeva, R., West, P., et al. (2021) · bioRxiv · doi:10.1101/2021.03.03.433784 · Cited by 3
Self-citationGhuneim, L.-A. J., Distaso, M. A., Chernikova, T. N., Bargiela, R., Lunev, E. A., Korzhenkov, A. A., Toshchakov, S. V., Rojo, D., Barbas, C., Ferrer, M., et al. (2020) · FEMS Microbiology Ecology · doi:10.1093/femsec/fiaa244 · Cited by 5
“For instance, a lack of biosynthetic pathways like for the synthesis of nucleic acids, vitamins and lipids, and mechanisms for DNA repair is commonplace for many symbiont species (Brown et al. 2015; Nelson and Stegen 2015).”
BackgroundLamont, E., Hendrickson, E., McLean, J., He, X., & Bor, B. (2020) · Microbiology Resource Announcements · doi:10.1128/mra.00810-20 · Cited by 3
“CPR organisms comprise 25% of all bacterial diversity and have an ultrasmall cell size and reduced genome (1, 3).”
BackgroundMeng, P., Lu, C., Lou, X., Zhang, Q., Jia, P., Yan, Z., Lin, J., & Chen, F. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/358812 · Cited by 8
Migrating SSU rRNA gene surveys to the metagenomics era.
Neufeld, J. (2017) · Environmental Microbiology Reports · doi:10.1111/1758-2229.12493 · Cited by 3
Delmont, T., & Eren, A. M. (2016) · bioRxiv · doi:10.1101/058750 · Cited by 3
“To explore microbial systems using metagenomeassembled genomes (MAGs), researchers often rely on functional annotations, phylogenetically informative conserved gene families, or distribution patterns to identify metabolic potentials [8], evolutionary relatedness [9, 10], or co-occurrence of genomic collections [11].”
BackgroundThe status of the microbial census: an update
Schloss, P., Girard, R., Martin, T. M., Edwards, J., & Thrash, J. (2016) · bioRxiv · doi:10.1101/038646 · Cited by 3
“preclude detection with standard PCR-based approaches (37, 38).”
MethodBacterial evolution: An intriguing new bacterial phylum
Attar, N. (2015) · Nature Reviews Microbiology · doi:10.1038/nrmicro3534 · Cited by 3
Bioremediation and Biotechnology, Vol 4: Techniques for Noxious Substances Remediation
Bhat, R., & Hakeem, K. R. (2020) · doi:10.1007/978-3-030-48690-7 · Cited by 3
Extremophile Microorganisms and Their Industrial Applications
Malik, K., Kumari, N., Ahlawat, S., Kumar, U., & Sindhu, M. (2020) · Springer eBooks · doi:10.1007/978-981-15-4099-8_10 · Cited by 3
Wang, E. T., & Young, J. P. W. (2019) · Springer eBooks · doi:10.1007/978-981-32-9555-1_2 · Cited by 5
Diversity, biogeography and assembly mechanisms of groundwater microbiomes
Wu, Z., Ning, D., Fields, M. W., Hazen, T. C., Adams, P. D., Arkin, A. P., & Zhou, J. Z. (2026) · Nature Reviews Earth & Environment · doi:10.1038/s43017-026-00813-y · Cited by 2
“It provides comprehensive genetic information of almost all microorganisms, thereby revealing functional potentials and phylogenetic taxonomy of bacteria, archaea and viruses in groundwater 9,10,22,126 .”
InfluentialRethinking metagenome-assembled genome completeness: are we truly recovering complete genomes?
Pellegrinetti, T., Molligan, J., Mendes, L. W., Pedrinho, A., & Pérez-López, E. (2026) · Frontiers in Microbiology · doi:10.3389/fmicb.2026.1884628 · Cited by 2
Hendrickson, E., Bor, B., He, X.-S., & McLean, J. S. (2026) · International Journal of Systematic and Evolutionary Microbiology · doi:10.1099/ijsem.0.007162 · Cited by 2
Parks, D., Chaumeil, P., Chuvochina, M., & Hugenholtz, P. (2026) · bioRxiv · doi:10.64898/2025.12.01.691617 · Cited by 2
“These 35 MAGs came from 27 SRA runs which have a minimum estimated CAVGFB01 or JAUNQF01 coverage of 6.8x and abundance of 0.17%.”
InfluentialMalina, N., Tollerson, R., Monami, S. J., Rivera, E., Lee, M.-K., Bilenker, L., & Ojeda, A. (2025) · Applied and Environmental Microbiology · doi:10.1128/aem.00988-25 · Cited by 2
Bioleaching Microbial Community Metabolism and Composition Driven by Copper Sulphide Mineral Type
Lane, K. R., Jones, S. E., Osborne, T. H., Geller‐McGrath, D., Nwaobi, B. C., Chen, L.-X., Thomas, B. C., Hudson-Edwards, K. A., Banfield, J. F., & Santini, J. M. (2025) · Environmental Microbiology Reports · doi:10.1111/1758-2229.70261 · Cited by 3
“Organisms were also binned automatically with ABAWACA (Brown et al. 2015) and metaBAT2 v2.”
Self-citationLv, Y.-X., Zhang, L.-Z., & Zhang, Y. (2025) · Microbiome · doi:10.1186/s40168-025-02192-w · Cited by 2
“Specifically, the quality of MAGs classified as Patescibacteria was based on the marker gene set [44].”
Viral ecogenomics across oxic and anoxic zones of the Yongle Blue Hole
Yang, M., Zhang, H., Zhou, Y.-L., Selvarajan, R., Xu, P., Gao, Z.-M., & Wang, Y. (2025) · Environmental Microbiome · doi:10.1186/s40793-025-00778-3 · Cited by 2
“Nota-bly, due to the simplified genomes of several prokaryotic hosts detected in YBH, such as Patescibacteria , Nanoar-chaeota , Aenigmatarchaeota and Altarchaeota [84, 86], viral infections may provide crucial AMGs that enhance its survival and adaptability in the relatively extreme environment.”
Yagi, S., Fukui, H., Shiraishi, T., Kaku, K., Wakita, M., Takagi, Y., Ikenouchi, M., Sato, T., Kawai, M., Yokoyama, Y., et al. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26199359 · Cited by 2
“…of Patescibacteria in human diseases is not fully understood, it represents a diverse group of bacteria accounting for a significant proportion of microbial dark matter [37] and is frequently detected in various environments, including groundwater, freshwater, and the human oral cavity [38–40].”
Gios, E., Mosley, O. E., Takeuchi, N., & Handley, K. M. (2025) · mSystems · doi:10.1128/msystems.00046-25 · Cited by 8
“…prokaryotes, genome completeness and contamination were assessed based on the presence of the following SCG sets: 43 SCGs for Patescibacteria (5), 51 bacterial single-copy genes (SCGs) for Dependentiae (89), and 38 archaeal SCGs for DPANN (89), using the method described by Brown et al. (5).”
Alibrandi, A., Plewka, J., Primio, R. D., Bartholomäus, A., Vuillemin, A., Probst, A. J., & Kallmeyer, J. (2025) · bioRxiv · doi:10.3389/fmicb.2026.1741638 · Cited by 2
“Scaolds with a minimum length of 1,000 bp were binned into MAGs using ABAWACA (v. 1.0.0) (Brown et al., 2015) and MaxBin2 (v. 2.2.7) (Wu et al., 2016) with default parameters.”
InfluentialYe, P.-Z., Yang, Q., Zhang, C.-Y., Yang, T.-T., Jiang, S.-F., Lan, R., Gao, S.-M., & Huang, L.-N. (2025) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2025.138862 · Cited by 2
Environmental diversity of Candidatus Babelota and their relationships with protists
Weisse, L., Martin, L., Moumen, B., Héchard, Y., & Delafont, V. (2025) · mSystems · doi:10.1128/msystems.00261-25 · Cited by 2
“matter (MDM) (5).”
Vigneron, A., Cloarec, L., Brochier-Armanet, C., Flandrois, J., Troussellier, M., Bernard, C., Agogué, H., Oger, P. M., & Hugoni, M. (2025) · Environmental Microbiome · doi:10.1186/s40793-025-00699-1 · Cited by 2
“…genomic, and functional diversities of the enigmatic Patescibacteria (bacterial Candidate Phyla Radiation) or DPANN archaea, has been significantly expanded by genome-centric metagenomics, revealing their ubiq-uity, abundance and complex entanglement with other microbial lineages [11, 12].”
Gunawardana, E. G., Sotelo, T. J., Oshima, K., Hattori, M., Mino, T., & Satoh, H. (2025) · Microbes and Environments · doi:10.1264/jsme2.me24082 · Cited by 2
“Bacteria in this group have been reported in ground‐ water filtrates (Nelson and Stegen, 2015; Brown et al. , 2015).”
InfluentialSchechter, M. S., Trigodet, F., Veseli, I., Miller, S. E., Klein, M. L., Sever, M., Maignien, L., Delmont, T. O., Light, S. H., & Eren, A. M. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.01.15.633187 · Cited by 4
“Indeed, the rapidly increasing number of microbial genomes (1) provides an evolutionary framework to resolve the branches of the Tree of Life (Brown et al. 2015; Spang et al. 2015), (2) enables hypothesis generation and testing through comparative genomics (Paoli et al. 2022; Al-Shayeb et al. 2022;…”
The right tool for the job: Chemical biology and microbiome science
Whidbey, C. (2025) · Cell chemical biology · doi:10.1016/j.chembiol.2024.12.004 · Cited by 2
Papaleo, S., Nodari, R., Sterzi, L., D'Auria, E., Cattaneo, C., Bettoni, G., Bonaiti, C., Pagliarini, E., Zuccotti, G., Panelli, S., et al. (2024) · PLoS ONE · doi:10.1371/journal.pone.0310675 · Cited by 2
Herbold, C. W., Noell, S. E., Lee, C. K., Vickers, C. J., Stott, M., Eisen, J., McDonald, I. R., & Cary, S. (2024) · Environmental Microbiome · doi:10.1186/s40793-024-00655-5 · Cited by 2
“Due to this distribution pattern and the fact that an accelerated evolutionary process is a hallmark feature of members of this lineage [31, 61, 62], we did not pursue further analysis of this genome, which would be best accomplished in a comprehensive comparison with other Ca. Patescibacteria.”
Evolutionary Flexibility of Ribosome Biogenesis in Bacteria
Amikura, K., Ishii, S., Shimizu, Y., & Suzuki, S. (2024) · bioRxiv · doi:10.1093/molbev/msaf288 · Cited by 2
Unique Features of Extremely Halophilic Microbiota Inhabiting Solar Saltworks Fields of Vietnam
Cono, V. L., Spada, G. L., Smedile, F., Crisafi, F., Marturano, L., Modica, A., Huynh, K. H. N., Pham, T. D., Hang, C. T. T., Selivanova, E. A., et al. (2024) · Microorganisms · doi:10.3390/microorganisms12101975 · Cited by 2
“Members of these newly discovered taxa are typically ultra-small in size, with an average cell diameter of 200–450 nm, and possess highly reduced genomes (average size 1 Mbp) and minimal cellular activities, including limited metabolic potential [31–33].”
BackgroundTrubl, G., Leleiwi, I., Campbell, A., Kimbrel, J. A., Bhattacharyya, A., Riley, R., Malmstrom, R., Blazewicz, S., & Pett-Ridge, J. (2024) · bioRxiv · doi:10.1101/2024.09.13.612973 · Cited by 2
Wong, M. L., Duckett, M., Hernandez, E. S., Rajaei, V., & Smith, K. J. (2024) · Perspectives of Earth and Space Scientists · doi:10.1029/2023cn000223 · Cited by 10
“The development of metagenomics and deep sequencing methods has revealed a more complete picture of the tree of life, unconstrained by culture methods previously predominant in microbiology (Al‐Shayeb et al., 2022; Brown et al., 2015; Hug et al., 2016; Shu & Huang, 2022).”
Analyzing microbial evolution through gene and genome phylogenies
Teichman, S., Lee, M. D., & Willis, A. (2023) · bioRxiv · doi:10.1101/2023.08.15.553440 · Cited by 2
“When pursuing phylogenomics, most microbial investigations estimate a single phylogeny that summarizes the evolution of a set of organisms (see, e.g., Brown et al. (2015); Parks et al. (2018); Imachi et al. (2020)).”
COBRA improves the quality of viral genomes assembled from metagenomesPreprint
Chen, L.-X., & Banfield, J. (2023) · bioRxiv · doi:10.1101/2023.05.30.542503 · Cited by 2
“To evaluate the performance of COBRA on non-viral genomes, we applied it to three published groundwater metagenomes, each containing hundreds of MAGs from Candidate Phyla Radiation (CPR) bacteria that typically have small genomes (~1 Mbp) 37 , as well as from other bacteria and archaea 38,39 .”
MethodSelf-citationAnaerobic Thermodesulfovibrio and Aerobic Meiothermus Coexist in Deep Thermal Water
Lukina, A., Kadnikov, V., Rusanov, I., Avakyan, M. R., Beletsky, A., Mardanov, A., Pimenov, N., Ravin, N., & Karnachuk, O. (2023) · Microbiology · doi:10.1134/s0026261723600234 · Cited by 2
“Patescibacteria possess small genomes (typically less than ~1 million nucleotides) and lack many essential biosynthetic pathways (Brown et al., 2015).”
BackgroundStructure and Seasonal Variability of Microbial Communities of Groundwater in the City of Moscow
Gruzdev, E. V., Begmatov, S., Beletsky, A., Mardanov, A. V., Ravin, N., & Kadnikov, V. (2023) · Microbiology · doi:10.1134/s0026261722603293 · Cited by 2
“Like Nanoarchaeota, Patescibacteria have small genomes (usually less than ~1 Mb) and lack many key biosynthetic pathways (Brown et al., 2015).”
BackgroundExpanded diversity of tfdA harboring bacteria across the natural and built environment
White, A., Vázquez, A. G. G., McDaniel, E., Peterson, B. D., Koch, P., Remucal, C., & McMahon, K. (2022) · bioRxiv · doi:10.1101/2022.09.28.509959 · Cited by 2
“Previous 204 work demonstrating uncultured microbes like Rokubacteria may use alternative metabolic 205 pathways that prevent their culturing under typical conditions (46, 51, 52) highlights the power of 206”
BackgroundHilts, A., Hunjan, M., & Hug, L. (2021) · bioRxiv · doi:10.1128/msystems.00790-21 · Cited by 2
Self-citationBaker, J. (2021) · Microbiology Resource Announcements · doi:10.1128/mra.00517-21 · Cited by 2
Reconstruction of Metagenome-Assembled Genomes from Aquaria
Ettinger, C., Bryan, J., Tokajian, S., Jospin, G., Coil, D., & Eisen, J. (2021) · bioRxiv · doi:10.1128/mra.00557-21 · Cited by 2
“CPR genome completion was then re-estimated using 43 single-copy marker genes, as CPR members are known to have missing single-copy genes (14).”
MethodDistinct hydrogenotrophic bacteria are stimulated by elevated H2 levels in upland and wetland soilsPreprint
Xu, Y.-F., Teng, Y., Dong, X.-Y., Wang, X.-M., Zhang, C., Ren, W.-J., Zhao, L., Luo, Y.-M., & Greening, C. (2020) · bioRxiv · doi:10.1101/2020.11.15.383943 · Cited by 2
“We also retrieved a surprising number of 180 Patescibacteria MAGs (17), supporting recent reports that these symbionts can be 181 abundant in oxygenated soils [78, 79].”
Moreira, D., Zivanovic, Y., López-Archilla, A., Iniesto, M., & López-García, P. (2020) · bioRxiv · doi:10.1101/2020.11.10.374967 · Cited by 2
Hwang, Y., Schulze-Makuch, D., Arens, F., Sáenz, J., Adam, P., Bornemann, T., Airo, A., Schloter, M., & Probst, A. (2020) · bioRxiv · doi:10.1101/2020.07.17.208546 · Cited by 2
Chitinases Encoded in the Genomes of Acidobacteria: Origin and Evolution
Naumoff, D. G., & Dedysh, S. (2020) · Microbiology · doi:10.1134/s0026261720040098 · Cited by 2
Sieber, C., Paul, B., Castelle, C., Hu, P., Tringe, S., Valentine, D. L., Andersen, G., & Banfield, J. (2019) · bioRxiv · doi:10.1101/595074 · Cited by 2
“The absence of these pathways raises two questions (1) the nature of central carbon metabolism in these organisms, and (2) how ATP, NADH, NADPH and ferredoxin are reduced and recycled.”
BackgroundSelf-citationCell-free DNA Reveals Potential Zoonotic Reservoirs in Non-Human PrimatesPreprint
Kowarsky, M., Vlaminck, I. D., Okamoto, J., Neff, N., Lebreton, M., Nwobegabay, J., Tamoufe, U., LeDoux, J. E., Tafon, B., Kiyang, J. A., et al. (2018) · bioRxiv · doi:10.1101/481093 · Cited by 2
Chen, L.-X., Al-Shayeb, B., Méheust, R., Li, W.-J., Doudna, J., & Banfield, J. (2018) · doi:10.1101/448639 · Cited by 2
Self-citationQuantifying biosynthetic network robustness across the human oral microbiome
Bernstein, D. B., Dewhirst, F., & Segrè, D. (2018) · bioRxiv · doi:10.1101/392621 · Cited by 2
The Impact of Agriculture on Soil Microbial Community Composition and Diversity in Southeast Asia
Tripathi, B., Moroenyane, I., & Adams, J. (2017) · doi:10.1002/9781119276050.ch2 · Cited by 2
Archaea as components of forest microbiome
Yrjälä, K., & Lopez‐Echartea, E. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822542-4.00014-0
Virus Discovery by Metagenomics: The (Im)possibilities
Dutilh, B., Reyes, A., Hall, R. J., & Whiteson, K. (n.d.) · doi:10.3389/978-2-88945-308-5 · Cited by 2
“Second, this reflects the diversity in the microbial world itself that includes giant viruses (Halary et al., 2016), tiny bacteria (Brown et al., 2015), and everything in between.”
Long, Y., Sun, L., Han, Y., Paengkoum, P., Paengkoum, S., Taethaisong, N., Meethip, W., Sanlakhon, A., Konkrathok, S., Kotsanthia, S., et al. (2026) · Animal Feed Science and Technology · doi:10.1016/j.anifeedsci.2026.117068 · Cited by 1
Metadata
- Authors
- Brown, C. T., Hug, L. A., Thomas, B. C., Sharon, I., Castelle, C. J., Singh, A., Wilkins, M. J., Wrighton, K. C., Williams, K. H., & Banfield, J. F.
- Affiliations
- University of California, Berkeley (US)
- The Ohio State University (US)
- Lawrence Berkeley National Laboratory (US)
- Corresponding author
- Banfield, Jillian F.
- ORCID
- Venue
- Nature
- Published
- 2015-06-15
- Volume
- 523
- Issue
- 7559
- Pages
- 208-211
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1528357204
- Cited by
- 1,216
- References
- 63
- Citations by year
- 2026: 56 · 2025: 100 · 2024: 95 · 2023: 125 · 2022: 108 · 2021: 120 · 2020: 144 · 2019: 121 · 2018: 116 · 2017: 104 · 2016: 101 · 2015: 26
- FWCI
- 50.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.osti.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- U.S. Department of Energy (DESC0004918, DE AC02 05CH11231)
- Joint Genome Institute
- Office of Science
- Biological and Environmental Research
- Pacific Northwest National Laboratory
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Physical Sciences › Environmental Science › Ecology › Microbial Community Ecology and Physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- Candidate Phyla Radiation, uncultured bacteria, bacterial evolution, ribosome composition, ribosome biogenesis, self-splicing introns, small genomes, groundwater bacteria, metagenome-assembled genomes, symbionts
- MeSH terms
- Bacteria, Environmental Microbiology, Introns, Phylogeny, Ribosomal Proteins, RNA, Ribosomal, 16S, Genome, Bacterial
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