Thousands of small, novel genes predicted in global phage genomes

• DOI: 10.1016/j.celrep.2022.110984
• Publication Date: 2022-06-21T14:47:24Z
• Authors: Brayon J. Fremin; Ami S. Bhatt; Nikos C. Kyrpides; Aditi Sengupta; Alexander Sczyrba; Aline Maria da Silva; Alison Buchan; Amelie Gaudin; Andreas Brune; Ann M. Hirsch; Anthony Neumann; Ashley Shade; Axel Visel; Barbara Campbell; Brett Baker; Brian P. Hedlund; Byron C. Crump; Cameron Currie; Charlene Kelly; Chris Craft; Christina Hazard; Christopher Francis; Christopher W. Sc...; Colin Averill; Courtney Mobilian; Dan Buckley; Dana Hunt; Daniel Noguera; David Beck; David L. Valentine; David Walsh; Dawn Sumner; Despoina Lymperop...; Devaki Bhaya; Donald A. Bryant; Elise Morrison; Eoin Brodie; Erica Young; Erik Lilleskov; Eva Högfors-Rönnholm; Feng Chen; Frank Stewart; Graeme W. Nicol; Hanno Teeling; Harry R. Beller; Hebe Dionisi; Hui-Ling Liao; J. Michael Beman; James Stegen; James Tiedje; Janet Jansson; Jean VanderGheynst; Jeanette Norton; Jeff Dangl; Jeffrey Blanchard; Jennifer Bowen; Jennifer Macalady; Jennifer Pett-Ridge; Jeremy Rich; Jérôme P. Payet; John D. Gladden; Jonathan D. Raff; Jonathan L. Klassen; Jonathan Tarn; Josh Neufeld; Kelly Gravuer; Kirsten Hofmockel; Ko-Hsuan Chen; Konstantinos Kons...; Kristen M. DeAngelis; Laila P. Partida-...; Laura Meredith; Ludmila Chistoser...; Mary Ann Moran; Matthew Scarborough; Matthew Schrenk; Matthew Sullivan; Maude David; Michelle A. O'Malley; Monica Medina; Mussie Habteselassie; Nicholas D. Ward; Nicole Pietrasiak; Olivia U. Mason; Patrick O. Sorensen; Paulina Estrada d...; Petr Baldrian; R. Michael McKay; Rachel Simister; Ramunas Stepanauskas; Rebecca Neumann; Rex Malmstrom; Ricardo Cavicchioli; Robert Kelly; Roland Hatzenpichler; Roman Stocker; Rose Ann Cattolico; Ryan Ziels; Rytas Vilgalys; Sara Blumer-Schuette; Sean Crowe; Simon Roux; Steven Hallam; Steven Lindow; Susan H. Brawley; Susannah Tringe; Tanja Woyke; Thea Whitman; Thomas Bianchi; Thomas Mock; Timothy Donohue; Timothy Y. James; Udaya C. Kalluri; Ulas Karaoz; Vincent Denef; Wen-Tso Liu; William Whitman; Yang Ouyang
• Keywords: 0301 basic medicine; 570; Global Phage Small Open Reading Frame (GP-SmORF) Consortium; gene families; small families; Medical Physiology; Bioinformatics and Computational Biology; small genes; 610; microbiome; comparative genomics; Genome, Viral; Microbiology; 03 medical and health sciences; Genetics; phage; 2.1 Biological and endogenous factors; Bacteriophages; Viral; Phylogeny; Genome; Microbiota; Human Genome; ta1183; CP: Microbiology; MetaRibo-Seq; Genomics; Biological Sciences; Biological sciences; Generic health relevance; Biochemistry and Cell Biology; sORFs; Biotechnology

Small genes (<150 nucleotides) have been systematically overlooked in phage genomes. We employ a large-scale comparative genomics approach to predict >40,000 small-gene families in ∼2.3 million phage genome contigs. We find that small genes in phage genomes are approximately 3-fold more prevalent than in host prokaryotic genomes. Our approach enriches for small genes that are translated in microbiomes, suggesting the small genes identified are coding. More than 9,000 families encode potentially secreted or transmembrane proteins, more than 5,000 families encode predicted anti-CRISPR proteins, and more than 500 families encode predicted antimicrobial proteins. By combining homology and genomic-neighborhood analyses, we reveal substantial novelty and diversity within phage biology, including small phage genes found in multiple host phyla, small genes encoding proteins that play essential roles in host infection, and small genes that share genomic neighborhoods and whose encoded proteins may share related functions.