Functional and evolutionary significance of unknown genes from uncultivated taxa

作者：Álvaro Rodríguez del Río, Joaquín Giner‐Lamia, Carlos P. Cantalapiedra, Jorge Botas, Ziqi Deng, Ana Hernández-Plaza, Martí Munar‐Palmer, Saray Santamaría‐Hernando, José J. Rodríguez‐Herva, Hans‐Joachim Ruscheweyh, Lucas Paoli, Thomas Schmidt, Shinichi Sunagawa, Peer Bork, Emilia López‐Solanilla, Luís Pedro Coelho, Jaime Huerta‐Cepas · 发表于：Nature · 年份：2023 · DOI：10.1038/s41586-023-06955-z · 被引用次数：105 · 研究领域：Genomics and Phylogenetic Studies、Microbial Community Ecology and Physiology、Protist diversity and phylogeny

Abstract Many of the Earth’s microbes remain uncultured and understudied, limiting our understanding of the functional and evolutionary aspects of their genetic material, which remain largely overlooked in most metagenomic studies 1 . Here we analysed 149,842 environmental genomes from multiple habitats 2–6 and compiled a curated catalogue of 404,085 functionally and evolutionarily significant novel (FESNov) gene families exclusive to uncultivated prokaryotic taxa. All FESNov families span multiple species, exhibit strong signals of purifying selection and qualify as new orthologous groups, thus nearly tripling the number of bacterial and archaeal gene families described to date. The FESNov catalogue is enriched in clade-specific traits, including 1,034 novel families that can distinguish entire uncultivated phyla, classes and orders, probably representing synapomorphies that facilitated their evolutionary divergence. Using genomic context analysis and structural alignments we predicted functional associations for 32.4% of FESNov families, including 4,349 high-confidence associations with important biological processes. These predictions provide a valuable hypothesis-driven framework that we used for experimental validatation of a new gene family involved in cell motility and a novel set of antimicrobial peptides. We also demonstrate that the relative abundance profiles of novel families can discriminate between environments and clinical conditions, leading to the discovery o...