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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The bacterial candidate phyla radiation (CPR) and the DPANN archaea diversify near the base of the Bacteria and Archaea respectively.
“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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Daly, R., Borton, M., Wilkins, M., Hoyt, D., Kountz, D. J., Wolfe, R. A., Welch, S., Marcus, D., Trexler, R., MacRae, J., et al. (2016) · Nature Microbiology · doi:10.1038/nmicrobiol.2016.146 · Cited by 228 · see citing works
Self-citationRecovering complete and draft population genomes from metagenome datasets
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“This method can be extrapolated to uncultured, unknown genomes without a close reference sequence [65, 66].”
BackgroundMethodInsights into the ecology, evolution, and metabolism of the widespread Woesearchaeotal lineages
Liu, X., Li, M., Castelle, C., Probst, A., Zhou, Z.-C., Pan, J., Liu, Y., Banfield, J., & Gu, J.-D. (2018) · Microbiome · doi:10.1186/s40168-018-0488-2 · Cited by 227 · see citing works
“[15, 27], sediment [28, 29], and freshwater [16].”
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Self-citationMarine mammals harbor unique microbiotas shaped by and yet distinct from the sea
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Opportunities and challenges of using metagenomic data to bring uncultured microbes into cultivation
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“used this method to culture Saccharibacteria (TM7), a phylum belonging to the bacterial candidate phyla radiation [109], from human saliva samples, which represented three different species-level lineages of Saccharibacteria.”
MethodThe nature of the last universal common ancestor and its impact on the early Earth system
Moody, E. R. R., Álvarez-Carretero, S., Mahendrarajah, T., Clark, J., Betts, H. C., Dombrowski, N., Szánthó, L. L., Boyle, R. A., Daines, S. J., Chen, X., et al. (2024) · Nature Ecology & Evolution · doi:10.1038/s41559-024-02461-1 · Cited by 256 · see citing works
“3), and a combination of both the DPANN and CPR constraints (topology 2); these were tested against the ML topo logy, both using the normal 20 amino acid alignments and also with Susko–Roger recoding 88 .”
InfluentialTransitory microbial habitat in the hyperarid Atacama Desert
Schulze-Makuch, D., Wagner, D., Kounaves, S., Mangelsdorf, K., Devine, K. G., de Vera, J. D., Schmitt-Kopplin, P., Grossart, H., Parro, V., Kaupenjohann, M., et al. (2018) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1714341115 · Cited by 222 · see citing works
“No rain can fall from the Martian atmosphere today (35), but liquid water can be present near the Martian surface in the form of nightly snow storms/ice microbursts (36), fog (37), near-surface groundwater (38), and possibly also from mineral dehydration reactions (39).”
BackgroundMethodIt’s the song, not the singer: an exploration of holobiosis and evolutionary theory
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“Shared metabolisms are part of the fabric of Nature (Falkowski et al. 2008): very recent metagenomic sequencing surveys have uncovered communities made up of multiple bacterial or archaeal cellular lineages whose genomes lack one or another gene necessary for independent growth (Brown et al. 2015).”
BackgroundShaiber, A., Willis, A. D., Delmont, T. O., Roux, S., Chen, L.-X., Schmid, A. C., Yousef, M., Watson, A. R., Lolans, K., Esen, Ö. C., et al. (2020) · Genome biology · doi:10.1186/s13059-020-02195-w · Cited by 227 · see citing works
Inference and reconstruction of the heimdallarchaeial ancestry of eukaryotes
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“The ggKbase genome bins were individually curated to fix local assembly errors using ra2.py 59 .”
Self-citationMetagenomics uncovers gaps in amplicon-based detection of microbial diversity
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PCycDB: a comprehensive and accurate database for fast analysis of phosphorus cycling genes
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“Also, it has been reported that about 20% of bacteria would be undetectable using currently available primers due to well-recognized biases [20].”
BackgroundHerrmann, M., Wegner, C., Taubert, M., Geesink, P., Lehmann, K., Yan, L.-J., Lehmann, R., Totsche, K., & Küsel, K. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.01407 · Cited by 210
“Patescibacteria depend on the uptake of nucleotides and amino acids from co-localized organisms (Brown et al., 2015).”
BackgroundInfluentialStarr, E. P., Nuccio, E., Pett-Ridge, J., Banfield, J., & Firestone, M. (2019) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1908291116 · Cited by 209 · see citing works
“com/christophertbrown/ fix_assembly_errors) (90).”
Self-citationReference standards for next-generation sequencing
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Resilience of the oral microbiome
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Self-citationSequence-based classification and identification of Fungi
Hibbett, D., Abarenkov, K., Kõljalg, U., Öpik, M., Chai, B., Cole, J., Wang, Q., Crous, P., Robert, V., Helgason, T., et al. (2016) · Mycologia · doi:10.3852/16-130 · Cited by 203 · see citing works
“Given the restrictions on naming uncultured species, microbiologists have made wide use of informal names for new species, as well as phyla and divisions (Brown et al. 2015, Spang et al. 2015).”
BackgroundSaccharibacteria (TM7) in the Human Oral Microbiome
Bor, B., Bedree, J. K., Shi, W., McLean, J. S., & He, X. (2019) · Journal of Dental Research · doi:10.1177/0022034519831671 · Cited by 228 · see citing works
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“The phylogenetic analyses also identified a new highly divergent lineage that branches as a sibling lineage to the CPR in the concatenated ribosomal protein tree (Fig.”
BackgroundInfluentialSelf-citationA distinct abundant group of microbial rhodopsins discovered using functional metagenomics
Pushkarev, A., Inoue, K., Larom, S., Flores‐Uribe, J., Singh, M. P., Konno, M., Tomida, S., Ito, S., Nakamura, R., Tsunoda, S. P., et al. (2018) · Nature · doi:10.1038/s41586-018-0225-9 · Cited by 230 · see citing works
Self-citationKarst, S. M., Dueholm, M. S., McIlroy, S. J., Kirkegaard, R. H., Nielsen, P. H., & Albertsen, M. (2018) · Nature Biotechnology · doi:10.1038/nbt.4045 · Cited by 218 · see citing works
Consistent Metagenome-Derived Metrics Verify and Delineate Bacterial Species Boundaries
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“Absent dramatic improvements in sequencing technologies, complex communities can be more fully characterized through analysis of assembled and unbinned single-copy marker genes, for example, the 16S rRNA gene, ribosomal genes, or tRNA-ligase genes (27–30).”
Self-citationBeresford-Jones, B. S., Forster, S. C., Stares, M. D., Notley, G., Viciani, E., Browne, H. P., Boehmler, D. J., Soderholm, A. T., Kumar, N., Vervier, K., et al. (2022) · Cell Host & Microbe · doi:10.1016/j.chom.2021.12.003 · Cited by 194 · see citing works
“For example, genomes of the large clade of uncultured bacteria, candidate phyla radiation (CPR), cannot be assigned a high-quality genome status using current single copy number gene methods (Brown et al., 2015).”
A decade of irrigation transforms the soil microbiome of a semi‐arid pine forest
Hartmann, M., Brunner, I., Hagedorn, F., Bardgett, R., Stierli, B., Herzog, C., Chen, X.-M., Zingg, A., Graf-Pannatier, E., Rigling, A., et al. (2017) · Molecular Ecology · doi:10.1111/mec.13995 · Cited by 194 · see citing works
“Members of these uncultured groups of bacteria have only recently been 337 characterized in more detail and feature small streamlined genomes with limited metabolic capabilities 338 and potentially symbiotic lifestyles (Brown et al. 2015; Youssef et al. 2015).”
BackgroundA census-based estimate of Earth's bacterial and archaeal diversity
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Megaphages infect Prevotella and variants are widespread in gut microbiomes
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Self-citationThe last universal common ancestor between ancient Earth chemistry and the onset of genetics
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“New insights about microbial phylogeny are emerging from concatenated alignments [24,29,30,42,48,68].”
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Methods for the extraction, storage, amplification and sequencing of DNA from environmental samples
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“Results can also generate clues about the lifestyle of candidate phyla that elude cultivation efforts (Wrighton et al. 2012; Kantor et al. 2013; Brown et al. 2015).”
BackgroundHug, L., Thomas, B., Sharon, I., Brown, C., Sharma, R., Hettich, R., Wilkins, M., Williams, K., Singh, A., & Banfield, J. (2016) · Environmental Microbiology · doi:10.1111/1462-2920.12930 · Cited by 185 · see citing works
Self-citation
- 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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