小柯机器人

西班牙马德里理工大学Jaime Huerta-Cepas团队揭示来自未培养类群的未知基因的功能和演化意义。这一研究成果于2023年12月18日在线发表在国际学术期刊《自然》上。

研究人员分析了来自多个栖息地的149842个环境基因组，并编制了一份包含404085个未培养原核生物类群独有的具有功能和演化意义的新基因（FESNov）家族的目录。所有FESNov基因家族都跨越多个物种，显示出强烈的纯化选择信号，并符合新的同源组的条件，因此几乎是迄今为止所描述的细菌和古细菌基因家族数量的三倍。FESNov目录具有丰富的支系特异性，其中有1034个新家族可以区分整个未培养门、类和目，很可能代表了促进其演化分化的共源性状。利用基因组上下文分析和结构比对，研究人员预测了32.4%的FESNov科的功能关联，其中包括4349个与重要生物过程相关的高置信度关联。

这些预测提供了一个有价值的假设驱动框架，研究人员利用该框架对一个参与细胞运动的新基因家族和一组新型抗菌肽进行了实验验证。研究人员还证明，新家族的相对丰度图谱可以区分不同的环境和临床状况，从而发现与结直肠癌相关的潜在新生物标志物。研究人员希望这项工作能加强未来的元基因组学研究，并扩大人们对未培养生物基因库的了解。

据介绍，地球上的许多微生物仍未被培养和研究，这限制了人们对其遗传物质的功能和演化方面的了解，而大多数元基因组研究在很大程度上忽视了这些方面。

附：英文原文

Title: Functional and evolutionary significance of unknown genes from uncultivated taxa

Author: Rodrguez del Ro, lvaro, Giner-Lamia, Joaqun, Cantalapiedra, Carlos P., Botas, Jorge, Deng, Ziqi, Hernndez-Plaza, Ana, Munar-Palmer, Mart, Santamara-Hernando, Saray, Rodrguez-Herva, Jos J., Ruscheweyh, Hans-Joachim, Paoli, Lucas, Schmidt, Thomas S. B., Sunagawa, Shinichi, Bork, Peer, Lpez-Solanilla, Emilia, Coelho, Luis Pedro, Huerta-Cepas, Jaime

Issue&Volume: 2023-12-18

Abstract: Many of Earth’s microbes remain uncultured and under-studied, limiting our understanding of the functional and evolutionary aspects of their genetic material, which remain largely overlooked in most metagenomic studies1. Here, we analyzed 149,842 environmental genomes from multiple habitats2–6 and compiled a curated catalog 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 catalog is enriched in clade-specific traits, including 1,034 novel families that can distinguish entire uncultivated phyla, classes, and orders, likely 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, which we employed to experimentally validate 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 of potentially new biomarkers associated with colorectal cancer. We expect this work to enhance future metagenomics studies and expand our knowledge of the genetic repertory of uncultivated organisms.

DOI: 10.1038/s41586-023-06955-z

Source: https://www.nature.com/articles/s41586-023-06955-z

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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