PT - JOURNAL ARTICLE AU - Al-Shayeb, Basem AU - Sachdeva, Rohan AU - Chen, Lin-Xing AU - Ward, Fred AU - Munk, Patrick AU - Devoto, Audra AU - Castelle, Cindy J. AU - Olm, Matthew R. AU - Bouma-Gregson, Keith AU - Amano, Yuki AU - He, Christine AU - Méheust, Raphaël AU - Brooks, Brandon AU - Thomas, Alex AU - Lavy, Adi AU - Matheus-Carnevali, Paula AU - Sun, Christine AU - Goltsman, Daniela S. A. AU - Borton, Mikayla A. AU - Nelson, Tara C. AU - Kantor, Rose AU - Jaffe, Alexander L. AU - Keren, Ray AU - Farag, Ibrahim F. AU - Lei, Shufei AU - Finstad, Kari AU - Amundson, Ronald AU - Anantharaman, Karthik AU - Zhou, Jinglie AU - Probst, Alexander J. AU - Power, Mary E. AU - Tringe, Susannah G. AU - Li, Wen-Jun AU - Wrighton, Kelly AU - Harrison, Sue AU - Morowitz, Michael AU - Relman, David A. AU - Doudna, Jennifer A AU - Lehours, Anne-Catherine AU - Warren, Lesley AU - Cate, Jamie H. D. AU - Santini, Joanne M. AU - Banfield, Jillian F. TI - Clades of huge phage from across Earth’s ecosystems AID - 10.1101/572362 DP - 2019 Jan 01 TA - bioRxiv PG - 572362 4099 - http://biorxiv.org/content/early/2019/03/11/572362.short 4100 - http://biorxiv.org/content/early/2019/03/11/572362.full 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.