Clades of huge phages from across Earth's ecosystems

Al-Shayeb, B.*; Sachdeva, R.*; Chen, L.-X.*; Ward, F.*; Munk, P.*; Devoto, A.*; Castelle, C. J.*; Olm, M. R.*; Bouma-Gregson, K.*; Amano, Yuki   ; He, C.*; Mheust, R.*; Brooks, B.*; Thomas, A.*; Lavy, A.*; Matheus-Carnevali, P.*; Sun, C.*; Goltsman, D. S. A.*; Borton, M. A.*; Sharrar, A.*; Jaffe, A. L.*; Nelson, T. C.*; Kantor, R.*; Keren, R.*; Lane, K. R.*; Farag, I. F.*; Lei, S.*; Finstad, K.*; Amundson, R.*; Anantharaman, K.*; Zhou, J.*; Probst, A. J.*; Power, M. E.*; Tringe, S. G.*; Li, W.-J.*; Wrighton, K.*; Harrison, S.*; Morowitz, M.*; Relman, D. A.*; Doudna, J. A.*; Lehours, A.-C.*; Warren, L.*; Cate, J. H. D.*; Santini, J. M.*; Banfield, J. F.*

Phage typically have small genomes and depend on their bacterial hosts for replication. We generated metagenomic datasets from many diverse ecosystems and reconstructed 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, initiation and elongation factors and ribosomal proteins. Phage CRISPR 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. Some phage repurpose bacterial systems for phage-defense to eliminate competing phage. We phylogenetically define seven major clades of huge phage from human and other animal microbiomes, oceans, lakes, sediments, soils and the built environment. We conclude that large gene inventories reflect a conserved biological strategy, observed across a broad bacterial host range and resulting in the distribution of huge phage across Earth's ecosystems.