A genome-phenome association study in native microbiomes identifies a mechanism for cytosine modification in DNA and RNA

eLife

Peter Weigele¹  Ira Schildkraut¹  Yan-Jiun Lee¹  Nan Dai¹  Ivan R Corrêa¹  Weiwei Yang¹  William Johnson¹  Romualdas Vaisvila¹  Laurence Ettwiller¹  Yu-Cheng Lin² 

[1] New England Biolabs, Ipswich, United States;New England Biolabs, Ipswich, United States;School of Dentistry, National Yang Ming Chiao Tung University, Taipei, Taiwan;

关键词: functional metagenomics;    DNA modification;    RNA modification;    5-hydroxymethylcytosine carbamoyltransferase;    GWAS;    microbiome;    MetaGPA;    Other;   

DOI  :  10.7554/eLife.70021

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY