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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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“Subsequent operation of bioinformatics research (http://www.drive5.com/usearch) and QIIME completed, such as statistics and drawing mainly using R, Python, and Java (Brown et al., 2015).”
MethodIrazoqui, J., Eberhardt, M. F., Santiago, G. M., & Amadio, A. (2023) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-023-12591-4 · Cited by 6
Dong, S., Xin, Y., Liu, C., Xiao, Y., Feng, X., & Liu, T. (2023) · Frontiers in Marine Science · doi:10.3389/fmars.2023.1084519 · Cited by 6
A first insight into the Polish Bochnia Salt Mine metagenome
Lach, J., Królikowska, K., Baranowska, M., Krupińska, M., Strapagiel, D., Matera-Witkiewicz, A., & Stączek, P. (2023) · Environmental science and pollution research international · doi:10.1007/s11356-023-25770-7 · Cited by 6
“6% of the microbiota composition of this site (Brown et al. 2015).”
BackgroundMycolicibacter acidiphilus sp. nov., an extremely acid-tolerant member of the genus Mycolicibacter.
Xia, J., Ni, G.-F., Wang, Y., Zheng, M., & Hu, S. (2022) · International Journal of Systematic and Evolutionary Microbiology · doi:10.1099/ijsem.0.005419 · Cited by 6
Genome Sequence of a New “Candidatus” Phylum “Dependentiae” Isolate from Chiba, Japan
Takemura, M. (2022) · Microbiology Resource Announcements · doi:10.1128/mra.01123-21 · Cited by 6
“addition to the metagenomic analysis (5).”
Tahon, G., Gök, D., Lebbe, L., & Willems, A. (2021) · Systematic and Applied Microbiology · doi:10.1016/j.syapm.2021.126250 · Cited by 6
Xie, B.-L., Wang, J., Nie, Y., Chen, D., Hu, B., Wu, X., & Du, W.-B. (2021) · bioRxiv · doi:10.1101/2021.07.08.451036 · Cited by 6
Momper, L., Casar, C., & Osburn, M. (2021) · bioRxiv · doi:10.1101/2021.05.06.442964 · Cited by 6
Bredin, Y. K., Hess, L., Scabin, A., Dunthorn, M., Haugaasen, T., Peres, C., Nilsson, H. R., Antonelli, A., & Ritter, C. (2021) · bioRxiv · doi:10.1101/2021.04.28.441795 · Cited by 6
“An interesting characteristic of Patescibacteria is the small size of their genomes (usually 1.5 Mbp) and their lack of biosynthetic capabilities (Brown et al., 2015).”
BackgroundInfluentialArchaeal roots of intramembrane aspartyl protease siblings signal peptide peptidase and presenilin
Raut, P., Glass, J., & Lieberman, R. (2020) · Proteins: Structure, Function, and Bioinformatics · doi:10.1002/prot.26009 · Cited by 6
“Because they have restricted genomes, many CPR bacteria and DPANN archaea are thought to live in symbiotic relationships.(66,67) Based on our phylogenetic analysis (Figure 1A), IAP”
BackgroundNicolas, A., Jaffe, A. L., Nuccio, E., Taga, M., Firestone, M., & Banfield, J. (2020) · bioRxiv · doi:10.1101/2020.07.13.194282 · Cited by 6
“This may be because isolation-based methods fail for organisms unable to grow alone and primers used in 16S rRNA gene surveys can have mismatches that preclude detection (11).”
MethodSelf-citationOverholt, W., Hölzer, M., Geesink, P., Diezel, C., Marz, M., & Küsel, K. (2019) · bioRxiv · doi:10.1101/2019.12.18.880807 · Cited by 6
“Here we focused on the Patescibacteria, since this group contains almost no cultivated representatives and they are often highly abundant in groundwater systems (Brown et al., 2015; Pedron et al., 2019).”
BackgroundRodriguez-R., L., Tsementzi, D., Luo, C., & Konstantinidis, K. (2019) · doi:10.1101/826941 · Cited by 6
“45 metagenomes (MAGs) are prefixed with a label in squared brackets indicating 1 the study from where they were derived, including: A13 [82], B15 [53], M18 [6], 2 P18 [83], and Z18 [84], as well as the current study (This study) or publicly 3 available data currently missing a published manuscript (Unpub).”
BackgroundSilva, M. O. D., Desmond, P., Derlon, N., Morgenroth, E., & Pernthaler, J. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.00843 · Cited by 6
Biological capacities clearly define a major subdivision in Domain BacteriaPreprint
Méheust, R., Burstein, D., Castelle, C., & Banfield, J. (2018) · bioRxiv · doi:10.1101/335083 · Cited by 6
“This monophyletic group were described as the Candidate Phyla Radiation (CPR) (Brown et al., 2015).”
BackgroundMethodInfluentialSelf-citationDramatic expansion of microbial groups that shape the global sulfur cycle
Anantharaman, K., Jungbluth, S., Kantor, R. S., Lavy, A., Warren, L., Rappé, M., Thomas, B., & Banfield, J. (2017) · bioRxiv · doi:10.1101/166447 · Cited by 6
Self-citationMetaG: a graph-based metagenomic gene analysis for big DNA data
Chowdhury, L., Khan, M. I., Deb, K., & Kamal, M. S. (2016) · Network Modeling Analysis in Health Informatics and Bioinformatics · doi:10.1007/s13721-016-0132-7 · Cited by 7
“While if two constructed genomes are similar, then combined genomes are transformed into common structures (Chang et al. 2015; Franzosa et al. 2014; Brown 2015; Wu et al. 2016; Brown et al. 2015; Kang et al. 2015; Gibbons et al. 2015; Deng et al. 2015).”
BackgroundGenetically Modified Microbes as Biofertilizers
Ali, R., Dijoo, Z. K., & Sajjad, N. (2020) · Springer eBooks · doi:10.1007/978-3-030-48690-7_13 · Cited by 19
Metabolic Potential of Candidatus Saccharimonadia Including Rare Lineages in Activated Sludge
Kagemasa, S., Kuroda, K., Nakai, R., Sato, M., Li, Y.-Y., & Kubota, K. (2025) · Environmental Microbiology Reports · doi:10.1111/1758-2229.70231 · Cited by 5
“…Candidatus Patescibacteria) (Nakajima et al. 2025) is a major bacterial phylogenetic group that includes various uncultivated classes, such as Candidatus Saccharimonadia, Candidatus Gracilibacteria, and Candidatus Microgenomatia, and represents > 15% of all bacterial diversity (Brown et al. 2015).”
InfluentialRuiz‐González, C., Mena, C., Cornejo‐Castillo, F. M., Romano‐Gude, D., Arandia‐Gorostidi, N., & Gasol, J. M. (2025) · mSystems · doi:10.1128/msystems.01125-25 · Cited by 4
“…surface and subsurface habitats, including marine, freshwater, soil, permafrost, plant rhizosphere ecosystems, or animal-associated habitats (27, 29–37), and even in the air (32, 38), but they are usually most abundant in oligotrophic and oxygen-poor groundwater environments (1, 6, 8, 9, 11, 24).”
InfluentialSessions, A. L., Magnabosco, C., Barton, H. A., Burkhardt, C., Dworkin, J. P., Freissinet, C., French, K. L., GLAVIN, D. P., Leys, N., Maixner, F., et al. (2025) · Astrobiology · doi:10.1177/15311074251382157 · Cited by 4
“…of microbial abundance due to multiple 16S rRNA gene copies in one bacterial genome (Louca et al., 2018), or underestimation of microbial abundance due to the inability of conventional 16S rRNA gene primers to capture entire clades of organisms (Brown et al., 2015; Eloe-Fadrosh et al., 2016).”
DPANN Archaea and CPR Bacteria: insights into early cellular evolution?
Mahendrarajah, T., & Spang, A. (2025) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2024.0096 · Cited by 6
“First of all, most DPANN and CPR representatives with reduced genomes appear to be symbionts that are obligately dependent on a host organism for growth and survival [17,21,26–31].”
Stach, T. L., Deep, A., Pimentel, I. M., Buchner, D., Borton, M., Soares, A., Starke, J., Bornemann, T. L. V., Rehsen, P. M., Dreger, K. L., et al. (2025) · ISME Communications · doi:10.1093/ismeco/ycaf079 · Cited by 8
“In brief, MetaBAT2 [61], ABAWACA [62], and MaxBin2 [63] were used as automatized tools and steps to achieve a manually curated and optimized bin set are described in the Supplementary Information.”
Chen, M., Grégoire, D. S., St-Germain, P., Berdugo-Clavijo, C., & Hug, L. A. (2025) · Science of the Total Environment · doi:10.1016/j.scitotenv.2025.179357 · Cited by 5
Self-citationQuiñonero-Coronel, M. D. M., Cabello-Yeves, P. J., Haro-Moreno, J., Rodríguez-Valera, F., & Garcillán-Barcia, M. (2025) · bioRxiv · doi:10.1099/mgen.0.001409 · Cited by 5
“One of these underexplored groups is the Candidate Phyla Radiation (CPR), which encompasses a strikingly diverse collection of ultra-small bacteria present in a variety of habitats with streamlined genomes [18].”
Wang, Y.-C., Lv, Y., Lin, Y.-T., Xue, Y.-M., Hu, X., Jiang, G.-Y., & Wang, C. (2024) · ACS ES&T Water · doi:10.1021/acsestwater.4c00103 · Cited by 5
Gago, J. F., Viver, T., Urdiain, M., Ferreira, E., Robledo, P., & Rossello-Mora, R. (2024) · Systematic and Applied Microbiology · doi:10.1016/j.syapm.2024.126506 · Cited by 5
Parsons, R. J., Liu, S., Longnecker, K., Yongblah, K., Johnson, C., Bolaños, L. M., Comstock, J., Opalk, K., Soule, M. C. K., Garley, R., et al. (2023) · Frontiers in Microbiology · doi:10.3389/fmicb.2023.1287477 · Cited by 5
Amorín, R., Conesa, A., & Foster, J. S. (2023) · Frontiers in Microbiology · doi:10.3389/fmicb.2023.1174685 · Cited by 6
“For instance, metagenomic sequencing has yielded evidence of dozens of new phyla as well as thousands of new taxa (Brown et al., 2015; Hug et al., 2016).”
BackgroundAn initial genomic blueprint of the healthy human oesophageal microbiome
Gilroy, R., Adam, M., Kumar, B., & Pallen, M. (2023) · Access Microbiology · doi:10.1099/acmi.0.000558.v3 · Cited by 5
“To estimate the completeness and contamination of suspected members of Candidate Phyla Radiation (CPR), we used 43 CPR specific markers [31] within CheckM retaining the quality thresholds described above for larger genomes.”
Maatouk, M., Rolain, J., & Bittar, F. (2023) · Microorganisms · doi:10.3390/microorganisms11051231 · Cited by 5
“This abundance is uncertain and depends on the type of analysis performed and the time it is carried out [7,12,25].”
BackgroundInfluentialGios, E., Mosley, O., Takeuchi, N., & Handley, K. M. (2022) · bioRxiv · doi:10.1101/2022.10.05.510940 · Cited by 5
Electrochemical Enrichment and Isolation of Electrogenic Bacteria from 0.22 µm Filtrate
Ihara, S., Wakai, S., Maehara, T., & Okamoto, A. (2022) · Microorganisms · doi:10.3390/microorganisms10102051 · Cited by 5
“22 μm filtrate, have a small genome (often <1 Mb) due to their symbiotic or parasitic lifestyle [4].”
BackgroundIbrahim, A., Maatouk, M., Raoult, D., & Bittar, F. (2022) · Microorganisms · doi:10.3390/microorganisms10030602 · Cited by 5
“These microorganisms present a particular lifestyle, represented by an obligatory physical attachment between them and a host cell (most often bacterial hosts), which could be either an exo-symbiotic or exo-parasitic relationship [3,6].”
BackgroundInfluentialOstenfeld, L. J., Munk, P., Aarestrup, F. M., & Otani, S. (2023) · PLoS ONE · doi:10.1371/journal.pone.0283676 · Cited by 6
The dark side of the ribosome life cycle
Ferreira-Cerca, S. (2022) · RNA Biology · doi:10.1080/15476286.2022.2121421 · Cited by 5
“In 2015, the same year where the Asgard archaea and CPR were first reported [61,75], Wiliam Sullivan wrote, independently of these discoveries, an essay entitled ‘The Institute for”
BackgroundHigh diversity and heterogeneity define microbial communities across an active municipal landfill
Sauk, A. H., & Hug, L. (2021) · bioRxiv · doi:10.1101/2021.03.26.437222 · Cited by 5
“196 Members of the Patescibacteria are often underrepresented in 16S rRNA gene amplicon studies 197 due to primer mismatches and long insertions in the gene [24], but can be more robustly 198 identified using metagenomic techniques [25].”
BackgroundSelf-citationBruno, A., Sandionigi, A., Magnani, D., Bernasconi, M., Pannuzzo, B., Consolandi, C., Camboni, T., Labra, M., & Casiraghi, M. (2021) · Frontiers in Ecology and Evolution · doi:10.3389/fevo.2021.615513 · Cited by 5
Importance of Candidate Phyla Radiation (CPR) Bacteria for the Origin of Life
Tsurumaki, M., Saito, M., Maruyama, S., & Kanai, A. (2020) · Journal of Geography (Chigaku Zasshi) · doi:10.5026/jgeography.129.881 · Cited by 5
Wan, Y., Song, F.-G., Wang, G.-Q., Liu, H., An, M., Wang, A., Wu, X., Ma, C.-X., & Wang, N. (2018) · Analytical Chemistry · doi:10.1021/acs.analchem.8b01933 · Cited by 5
Banfield, J., Anantharaman, K., Williams, K., & Thomas, B. (2017) · Genome Announcements · doi:10.1128/genomea.01299-17 · Cited by 5
Self-citationGenomes From Uncultivated Microorganisms
Woyke, T., Doud, D. F. R., & Eloe‐Fadrosh, E. A. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-809633-8.90682-4 · Cited by 5
Nakai, R., Imura, S., & Naganuma, T. (2019) · Springer Polar Sciences · doi:10.1007/978-3-030-02786-5_2 · Cited by 5
SandTraps are efficient, scalable, and mild systems for harvesting, washing and concentrating cells.
Frauenstein, D., Seidel, K., & Adrian, L. (2017) · Journal of Microbiological Methods · doi:10.1016/j.mimet.2016.11.018 · Cited by 5
Bouderka, F., López-García, P., Deschamps, P., Zhou, Y., Krupovic, M., Gutiérrez-Preciado, A., Ciobanu, M., Bertolino, P., David, G., Moreira, D., et al. (2026) · mBio · doi:10.1128/mbio.00025-26 · Cited by 5
“Genes coding for most ribosomal proteins were present ( n = 51) , with only a few missing, such as rpL30 , which is often absent in other symbiotic bacteria (2, 8).”
History of the Hadean “Living Microfossil” OD1 and Ultra-reducing Environments
Sato, T., Yoshiya, K., & Maruyama, S. (2019) · Journal of Geography (Chigaku Zasshi) · doi:10.5026/jgeography.128.571 · Cited by 12
“Among these places, the Hakuba-Happo serpentine-hosted hydrothermal system is a unique crossroad of the volcanic front of the island arc and peridotite accreted in ca. 580 Ma. ― 576― 統群に細分化し,その 1つを「OD1」(OP11Derived 1:OP11から派生した系統群その 1) と名づけた(Harris et al., 2004)。その後,国 際共同研究グループによって OD1のゲノムが解 読され,OD1は「Parcubacteria」(つま…”
InfluentialUnveiling Global Diversity of Patescibacteriota and Functional Interactions with Host Microbes
Ji, Y.-H., Liu, X., Zhao, S., Zhou, S.-H., Yang, Y., Zhang, P., Shi, Y., Qin, W., Zhu, G.-B., Zhu, Y.-G., et al. (2025) · Advancement of science · doi:10.1002/advs.202509416 · Cited by 4
Samuel, P., & Lopez, J. V. (2025) · Frontiers in Water · doi:10.3389/frwa.2025.1678547 · Cited by 4
Wang, Y.-H., Xu, H.-T., Liu, M., Yuan, B.-J., Gao, X., Zhang, X.-H., Tian, H.-D., Yu, H., Lai, J.-R., Liu, L., et al. (2025) · Microbiology spectrum · doi:10.1128/spectrum.00858-25 · Cited by 4
“As a result, species so defined may be a mixture of phenotypically and, especially, biologically different bacteria (28, 29).”
Zhou, S., Goto, S., & Urase, T. (2025) · Journal of Water Process Engineering · doi:10.1016/j.jwpe.2025.108182 · Cited by 4
Oren, A., Kostovski, M., & Göker, M. (2025) · International Journal of Systematic and Evolutionary Microbiology · doi:10.1099/ijsem.0.006772 · Cited by 4
Li, Y., Wu, Y.-H., Wang, H.-B., Wang, R.-N., Li, P., Huang, B.-H., & Hu, H.-Y. (2025) · Environmental Research · doi:10.1016/j.envres.2025.120905 · Cited by 4
The perennially ice-covered Lake Enigma, Antarctica supports unique microbial communities
Smedile, F., Cono, V. L., Urbini, S., Benedetti, G., Spada, G. L., Crisafi, F., Azzaro, M., Porcino, N., Fazi, S., Amalfitano, S., et al. (2024) · Communications Earth & Environment · doi:10.1038/s43247-024-01842-5 · Cited by 4
“This agrees with previous studies in which free-living ultrasmall Patescibacteria cells were enriched using fi ne-pore fi lters 86,93,94 .”
Lyons, K. J., Yapiyev, V., Lehosmaa, K., Ronkanen, A.-K., Rossi, P. M., & Kujala, K. (2024) · Water Research · doi:10.1016/j.watres.2024.122812 · Cited by 4
Táncsics, A., Bedics, A., Banerjee, S., Soares, A., Baka, E., Probst, A. J., & Kriszt, B. (2024) · Biologia Futura · doi:10.1007/s42977-024-00232-4 · Cited by 4
“Subsequently, Abawaca Brown et al. (2015) was run twice, first to include reads with a minimal length of 3000 base pairs (bps) and sequences split after 5000 bps and second to set the minimal scaffold length of 5000 bps and sequences split after 10,000 bps. MaxBin2 Wu et al. (2016) was also run on…”
Toward a Natural History of Microbial Life
Magnabosco, C., Husain, F., Paoletti, M. M., Parsons, C., Payette, J. G., Schwartz, S. L., Tamre, E., & Fournier, G. P. (2024) · Annual Review of Earth and Planetary Sciences · doi:10.1146/annurev-earth-031621-070542 · Cited by 11
Whitman, W. B., & Venter, S. (2024) · Systematic and Applied Microbiology · doi:10.1016/j.syapm.2024.126524 · Cited by 4
Peñalver, M., Paradela, A., Palacios-Cuéllar, C., Pucciarelli, M., & Portillo, F. G.-D. (2024) · Environmental Microbiology · doi:10.1111/1462-2920.16621 · Cited by 4
Kifushi, M., Nishikawa, Y., Hosokawa, M., Ide, K., Kogawa, M., Anai, T., & Takeyama, H. (2024) · Journal of Bioscience and Bioengineering · doi:10.1016/j.jbiosc.2024.02.007 · Cited by 4
Pathogen-microbiome interactions and the virulence of an entomopathogenic fungus
Kolp, M. R., Acosta, Y. D. A., Brewer, W. T., Nichols, H. L., Goldstein, E. B., Tallapragada, K., & Parker, B. J. (2024) · Applied and Environmental Microbiology · doi:10.1128/aem.02293-23 · Cited by 5
Zhang, X.-X., Bi, L., Gentekaki, E., Zhao, J.-M., Shen, P., & Zhang, Q.-Q. (2023) · Microorganisms · doi:10.3390/microorganisms11061500 · Cited by 4
“These microbial communities are a primary source of prey and also symbionts for marine heterotrophic ciliates [33,34].”
Background
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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