A Genome-Phenome Association study in native microbiomes identifies a mechanism for cytosine modification in DNA and RNA
- New England Biolabs Inc, United States
Abstract
Shotgun metagenomic sequencing is a powerful approach to study microbiomes in an unbiased manner and of increasing relevance for identifying novel enzymatic functions. However, the potential of metagenomics to relate from microbiome composition to function has thus far been underutilized. Here, we introduce the Metagenomics Genome-Phenome Association (MetaGPA) study framework, which allows linking genetic information in metagenomes with a dedicated functional phenotype. We applied MetaGPA to identify enzymes associated with cytosine modifications in environmental samples. From the 2365 genes that met our significance criteria, we confirm known pathways for cytosine modifications and proposed novel cytosine-modifying mechanisms. Specifically, we characterized and identified a novel nucleic acid modifying enzyme, 5-hydroxymethylcytosine carbamoyltransferase, that catalyzes the formation of a previously unknown cytosine modification, 5-carbamoyloxymethylcytosine, in DNA and RNA. Our work introduces MetaGPA as a novel and versatile tool for advancing functional metagenomics.
Data availability
All raw and processed sequencing data generated in this study have been submitted to the NCBI Sequence Read Archive (SRA; https://www.ncbi.nlm.nih.gov/sra) under accession number PRJNA714147.
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Metagenomics genotype and phenotype association analysis on DNA modificationNCBI Sequence Read Archive, PRJNA714147.
Article and author information
Author details
Laurence Ettwiller
Funding
New England Biolabs (no data)
- Weiwei Yang
- Yu-Cheng Lin
- William Johnson
- Nan Dai
- Romualdas Vaisvila
- Peter Weigele
- Yan-Jiun Lee
- Ivan R Corrêa Jr
- Ira Schildkraut
- Laurence Ettwiller
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- María Mercedes Zambrano, CorpoGen, Colombia
Version history
- Preprint posted: March 23, 2021 (view preprint)
- Received: May 4, 2021
- Accepted: November 5, 2021
- Accepted Manuscript published: November 8, 2021 (version 1)
- Version of Record published: December 14, 2021 (version 2)
Copyright
© 2021, Yang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A Genome-Phenome Association study in native microbiomes identifies a mechanism for cytosine modification in DNA and RNA
eLife 10:e70021.
https://doi.org/10.7554/eLife.70021
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