Journal
NATURE
Volume 578, Issue 7795, Pages 425-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41586-020-2007-4
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Funding
- National Institutes of Health (NIH) [RAI092531A, R01-GM109454]
- Alfred P. Sloan Foundation [APSF-2012-10-05]
- National Science Foundation (NSF) Sustainable Chemistry grant [1349278]
- NSF Graduate Research Fellowships [DGE 1752814, DGE 1106400]
- Paul Allen Foundation Frontiers Group
- Chan Zuckerberg Biohub
- Innovative Genomics Institute
- Novo Nordisk Foundation [NNF16OC0021856]
- NASA [13R-0043]
- CA AES
- German Science Foundation [DFG PR 1603/1-1]
- Camille & Henry Dreyfus Postdoctoral Fellowship in Environmental Chemistry
- US Department of Energy, Office of Science, Office of Biological and Environmental Research [DE-AC02-05CH11231]
- NSF [GRT00048468, 1342701, CHE-1740549]
- Ministry of Economy, Trade and Industry of Japan
- March of Dimes Prematurity Research Center at Stanford University School of Medicine
- Thomas C. and Joan M. Merigan Endowment at Stanford University
- National Research Foundation of South Africa [UID 64877]
- NSF CZO
- Directorate For Geosciences [1349278] Funding Source: National Science Foundation
- Division Of Earth Sciences [1349278] Funding Source: National Science Foundation
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Bacteriophages typically have small genomes(1) and depend on their bacterial hosts for replication(2). Here we sequenced DNA from diverse ecosystems and found hundreds of phage genomes with lengths of more than 200 kilobases (kb), including a genome of 735 kb, which is-to our knowledge-the largest phage genome to be described to date. Thirty-five genomes were manually curated to completion (circular and no gaps). Expanded genetic repertoires include diverse and previously undescribed CRISPR-Cas systems, transfer RNAs (tRNAs), tRNA synthetases, tRNA-modification enzymes, translation-initiation and elongation factors, and ribosomal proteins. The CRISPR-Cas systems of phages have the capacity to silence host transcription factors and translational genes, potentially as part of a larger interaction network that intercepts translation to redirect biosynthesis to phage-encoded functions. In addition, some phages may repurpose bacterial CRISPR-Cas systems to eliminate competing phages. We phylogenetically define the major clades of huge phages from human and other animal microbiomes, as well as from oceans, lakes, sediments, soils and the built environment. We conclude that the large gene inventories of huge phages reflect a conserved biological strategy, and that the phages are distributed across a broad bacterial host range and across Earth's ecosystems. Genomic analyses of major clades of huge phages sampled from across Earth's ecosystems show that they have diverse genetic inventories, including a variety of CRISPR-Cas systems and translation-relevant genes.
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