Abstract

Over the past thirty years, since the dawn of metagenomic studies, a completely new (micro) universe was revealed, with the potential to have profound impacts on many aspects of the society. Remarkably, the study of human microbiome provided a new perspective on a myriad of human traits previously regarded as solely (epi-) genetically encoded, such as disease susceptibility, immunological response, and social and nutritional behaviors. In this context, metagenomics has established a powerful framework for understanding the intricate connections between human societies and microbial communities, ultimately allowing for the optimization of both human health and productivity. Thus, we have shifted from the old concept of microbes as harmful organisms to a broader panorama, in which the signal of the relationship between humans and microbes is flexible and directly dependent on our own decisions and practices. In parallel, metagenomics has also been playing a major role in the prospection of “hidden” genetic features and the development of biotechnological applications, through the discovery of novel genes, enzymes, pathways, and bioactive molecules with completely new or improved biochemical functions. Therefore, this review highlights the major milestones over the last three decades of metagenomics, providing insights into both its potentialities and current challenges.

Highlights

  • About thirty years ago, in 1986, Pace and collaborators [1] proposed, for the first time, the revolutionary idea of cloning DNA directly from environmental samples to analyze the complexity of natural microbial populations (Figure 1, indicated as M2)

  • A new frontier in science was emerging—the mining for novel chemical compounds from uncultured microorganisms, which comprises more than 99% of the microbial diversity [3]

  • The so-called structural metagenomic approach, the main focus is to study the structure of the uncultivated microbial population, which can be expanded to other properties, such as the reconstruction of the complex metabolic network established between community members (Figure 2) [4, 5]

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Summary

Introduction

In 1986, Pace and collaborators [1] proposed, for the first time, the revolutionary idea of cloning DNA directly from environmental samples to analyze the complexity of natural microbial populations (Figure 1, indicated as M2). M8: Sequencing of the sargasso sea by Venter et al. In the first one, the so-called structural metagenomic approach, the main focus is to study the structure of the uncultivated microbial population, which can be expanded to other properties, such as the reconstruction of the complex metabolic network established between community members (Figure 2) [4, 5]. Structural metagenomics aims to investigate the genomes of the microbial community members In this sense, the later approach allows the overall reconstruction of the community structure, potentially revealing metabolic pathways of the whole microbiome and assigning minor or major geoecological roles to community members [4, 6, 9, 10].

Milestones in Metagenomics
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