The importance of tens of thousands of previously unexplored microbial genes

by time news

2023-12-20 15:45:48

For more than two decades, scientists from around the world have contributed to revealing the immense diversity of microorganisms that inhabit the different ecosystems of our planet, from oceans and soils, to our own body. Metagenomics, the field in charge of studying genetic material (DNA) obtained directly from environmental samples, has made it possible, for example, to identify thousands of new species and obtain new and revealing data on a good part of their genetic content. However, because most of these microorganisms have not yet been isolated in the laboratory, fundamental aspects about their genomes are unknown.

A new study provides key information to understand this large amount of unknown DNA, revealing its functional and evolutionary importance. The work, directed by Dr. Jaime Huerta Cepas from the Comparative Genomics and Metagenomics group of the Center for Plant Biotechnology and Genomics (CBGP), a joint center between the INIA National Center of the Higher Council for Scientific Research (CSIC) and the University Politécnica de Madrid (UPM), in Spain, all these entities, provide an extensive catalog of new gene families and highlight the need to incorporate this information in future metagenomic studies.

Dr. Huerta-Cepas points out that, although current metagenomic databases contain millions of unknown DNA sequences that code for new genes, the lack of information about their origin and biological relevance has greatly limited their integration into studies on the microbiome. . According to Dr. Huerta-Cepas, the characterization of this enormous number of new genes will allow us not only to discover new molecular functions, but also to better understand the interactions between microorganisms and their environment.

In the work, more than 149,000 microbial genomes obtained from various environments were examined, establishing a catalog of approximately 400,000 new gene families. Dr. Álvaro Rodríguez del Río, main author of the research, comments how, through comparative genomics and phylogenetic techniques, they have managed to identify many genes that, despite being absent in already known microorganisms, are highly prevalent in different ecosystems and are subjected to strong selective pressure. According to Dr. Rodríguez del Río, the identification of these gene families was based on very strict filters, discarding more than 90% of the available genetic material. Even so, the published catalog manages to triple the number of microbial gene families known to date.

This comprehensive analysis of the microbiome also provides functional information on more than 130,000 new gene families. To achieve this, various genomic conservation analyzes and protein structure prediction techniques based on artificial intelligence were used. The work highlights the practical application of these predictions in the discovery and characterization of new molecular functions, leading to experimental validation of several new genes involved in the mobility and defense mechanisms of microorganisms.

Artistic recreation of bacteria and part of their DNA. (Amazings Illustration / NCYT)

Finally, the study demonstrates how this large amount of genetic material, until now ignored, allows improving association studies between the microbiome and its environment. In particular, the study reveals how the abundance of some of these new genes varies significantly in the intestinal microbiome of patients with colon cancer. This discovery not only promises to improve diagnostic techniques, but also opens new avenues for a better understanding of the mechanisms that govern the relationship between microbiome and health.

An interdisciplinary team of CBGP researchers specialized in computational biology participated in the work (Dr. Jaime Huerta-Cepas, Dr. Álvaro Rodríguez del Río, Dr. Joaquín Giner Lamia, Dr. Carlos Pérez Cantalapiedra, Ana Hernandez Plaza, Ziqi Deng and Jorge Botas), as well as several members of the group led by Dr. Emilia Lopez Solanilla (Martí Munar-Palmer, Dr. Saray Santamaría-Hernando and Dr. José J. Rodríguez Herva), in charge of carrying out the experimental validations of some of the new microbial genes identified. Furthermore, this study has had the collaboration of the laboratories directed by Dr. Luis Pedro Coelho (Fudan University), Dr. Sinichi Sunagawa (ETH, Switzerland) and Dr. Peer Bork (EMBL, Germany), involved in the metagenomic data mining and protein structure prediction.

The study is titled “Functional and evolutionary significance of unknown genes from uncultivated taxa.” And it has been published in the academic journal Nature. (Source: UPM)

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