RT Journal Article SR Electronic T1 Clades of huge phage from across Earth’s ecosystems JF bioRxiv FD Cold Spring Harbor Laboratory SP 572362 DO 10.1101/572362 A1 Al-Shayeb, Basem A1 Sachdeva, Rohan A1 Chen, Lin-Xing A1 Ward, Fred A1 Munk, Patrick A1 Devoto, Audra A1 Castelle, Cindy J. A1 Olm, Matthew R. A1 Bouma-Gregson, Keith A1 Amano, Yuki A1 He, Christine A1 Méheust, Raphaël A1 Brooks, Brandon A1 Thomas, Alex A1 Lavy, Adi A1 Matheus-Carnevali, Paula A1 Sun, Christine A1 Goltsman, Daniela S. A. A1 Borton, Mikayla A. A1 Nelson, Tara C. A1 Kantor, Rose A1 Jaffe, Alexander L. A1 Keren, Ray A1 Farag, Ibrahim F. A1 Lei, Shufei A1 Finstad, Kari A1 Amundson, Ronald A1 Anantharaman, Karthik A1 Zhou, Jinglie A1 Probst, Alexander J. A1 Power, Mary E. A1 Tringe, Susannah G. A1 Li, Wen-Jun A1 Wrighton, Kelly A1 Harrison, Sue A1 Morowitz, Michael A1 Relman, David A. A1 Doudna, Jennifer A A1 Lehours, Anne-Catherine A1 Warren, Lesley A1 Cate, Jamie H. D. A1 Santini, Joanne M. A1 Banfield, Jillian F. YR 2019 UL http://biorxiv.org/content/early/2019/03/11/572362.abstract AB Phage typically have small genomes and depend on their bacterial hosts for replication. DNA sequenced from many diverse ecosystems revealed hundreds of huge phage genomes, between 200 kbp and 716 kbp in length. Thirty-four genomes were manually curated to completion, including the largest phage genomes yet reported. Expanded genetic repertoires include diverse and new CRISPR-Cas systems, tRNAs, tRNA synthetases, tRNA modification enzymes, translation initiation and elongation factors, and ribosomal proteins. Phage CRISPR-Cas systems 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 phage may repurpose bacterial CRISPR-Cas systems to eliminate competing phage. We phylogenetically define major clades of huge phage from human and other animal microbiomes, oceans, lakes, sediments, soils and the built environment. We conclude that their large gene inventories reflect a conserved biological strategy, observed over a broad bacterial host range and across Earth’s ecosystems.