TY - JOUR

T1 - Analysis of metagenome-assembled viral genomes from the human gut reveals diverse putative CrAss-like phages with unique genomic features

AU - Yutin, Natalya

AU - Benler, Sean

AU - Shmakov, Sergei A.

AU - Wolf, Yuri I.

AU - Tolstoy, Igor

AU - Rayko, Mike

AU - Antipov, Dmitry

AU - Pevzner, Pavel A.

AU - Koonin, Eugene V.

N1 - Funding Information: The authors thank Ayal Gussow for help with the prediction of Acrs, Kira Makarova for help with sequence analysis, and Koonin group members for useful discussions. N.Y., S.B., S.A.S., Y.I.W., and E.V.K. are supported by the Intramural Research Program of the National Institutes of Health of the USA (National Library of Medicine); P.A.P. is supported by the NSF/MCB-BSF grant 1715911. Publisher Copyright: © 2021, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/12

Y1 - 2021/12

N2 - CrAssphage is the most abundant human-associated virus and the founding member of a large group of bacteriophages, discovered in animal-associated and environmental metagenomes, that infect bacteria of the phylum Bacteroidetes. We analyze 4907 Circular Metagenome Assembled Genomes (cMAGs) of putative viruses from human gut microbiomes and identify nearly 600 genomes of crAss-like phages that account for nearly 87% of the DNA reads mapped to these cMAGs. Phylogenetic analysis of conserved genes demonstrates the monophyly of crAss-like phages, a putative virus order, and of 5 branches, potential families within that order, two of which have not been identified previously. The phage genomes in one of these families are almost twofold larger than the crAssphage genome (145-192 kilobases), with high density of self-splicing introns and inteins. Many crAss-like phages encode suppressor tRNAs that enable read-through of UGA or UAG stop-codons, mostly, in late phage genes. A distinct feature of the crAss-like phages is the recurrent switch of the phage DNA polymerase type between A and B families. Thus, comparative genomic analysis of the expanded assemblage of crAss-like phages reveals aspects of genome architecture and expression as well as phage biology that were not apparent from the previous work on phage genomics.

AB - CrAssphage is the most abundant human-associated virus and the founding member of a large group of bacteriophages, discovered in animal-associated and environmental metagenomes, that infect bacteria of the phylum Bacteroidetes. We analyze 4907 Circular Metagenome Assembled Genomes (cMAGs) of putative viruses from human gut microbiomes and identify nearly 600 genomes of crAss-like phages that account for nearly 87% of the DNA reads mapped to these cMAGs. Phylogenetic analysis of conserved genes demonstrates the monophyly of crAss-like phages, a putative virus order, and of 5 branches, potential families within that order, two of which have not been identified previously. The phage genomes in one of these families are almost twofold larger than the crAssphage genome (145-192 kilobases), with high density of self-splicing introns and inteins. Many crAss-like phages encode suppressor tRNAs that enable read-through of UGA or UAG stop-codons, mostly, in late phage genes. A distinct feature of the crAss-like phages is the recurrent switch of the phage DNA polymerase type between A and B families. Thus, comparative genomic analysis of the expanded assemblage of crAss-like phages reveals aspects of genome architecture and expression as well as phage biology that were not apparent from the previous work on phage genomics.

KW - Bacteriophages/genetics

KW - Codon/genetics

KW - Conserved Sequence

KW - DNA-Directed DNA Polymerase/metabolism

KW - Gastrointestinal Microbiome/genetics

KW - Genome, Viral

KW - Humans

KW - Inteins

KW - Introns/genetics

KW - Metagenome

KW - Open Reading Frames/genetics

KW - Phylogeny

KW - RNA Splicing/genetics

KW - Transcription, Genetic

KW - Virome/genetics

KW - ALIGNMENT

KW - SEQUENCE

UR - http://www.scopus.com/inward/record.url?scp=85100926516&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/e228c1d5-233f-32f5-bae7-a7b0da3e6365/

U2 - https://doi.org/10.1038/s41467-021-21350-w

DO - https://doi.org/10.1038/s41467-021-21350-w

M3 - Article

C2 - 33594055

AN - SCOPUS:85100926516

VL - 12

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 1044

ER -