From cultured to uncultured genome sequences: metagenomics and modeling microbial ecosystems.

Daniel R Garza,Bas E Dutilh

doi:10.1007/s00018-015-2004-1

Abstract

Microorganisms and the viruses that infect them are the most numerous biological entities on Earth and enclose its greatest biodiversity and genetic reservoir. With strength in their numbers, these microscopic organisms are major players in the cycles of energy and matter that sustain all life. Scientists have only scratched the surface of this vast microbial world through culture-dependent methods. Recent developments in generating metagenomes, large random samples of nucleic acid sequences isolated directly from the environment, are providing comprehensive portraits of the composition, structure, and functioning of microbial communities. Moreover, advances in metagenomic analysis have created the possibility of obtaining complete or nearly complete genome sequences from uncultured microorganisms, providing important means to study their biology, ecology, and evolution. Here we review some of the recent developments in the field of metagenomics, focusing on the discovery of genetic novelty and on methods for obtaining uncultured genome sequences, including through the recycling of previously published datasets. Moreover we discuss how metagenomics has become a core scientific tool to characterize eco-evolutionary patterns of microbial ecosystems, thus allowing us to simultaneously discover new microbes and study their natural communities. We conclude by discussing general guidelines and challenges for modeling the interactions between uncultured microorganisms and viruses based on the information contained in their genome sequences. These models will significantly advance our understanding of the functioning of microbial ecosystems and the roles of microbes in the environment.

Highlights

Metagenomics is the study of genetic material recovered directly from environmental samples in an untargeted way
The goal of this review is to introduce some of the recent landmarks of metagenomics in providing new insights into the uncultured microbial biosphere, and highlight the promises and challenges these new genome sequences bring for modeling natural microbial ecosystems
Novel strategies to sample and sequence environmental metagenomes as well as significant advances in bioinformatics and data recycling are increasing our knowledge of uncultured microorganisms

Summary

Introduction

Metagenomics is the study of genetic material recovered directly from environmental samples in an untargeted (shotgun) way. Among the commonly suggested causes for the plate count anomaly, we can list (1) lack of essential nutrients in the isolation media [18,19,20]; (2) lack of an essential biological interdependency with other species, such as auxotrophs or obligate mutualists [21,22,23]; (3) poor correlation between the in vitro growth condition and the environment: e.g. the media are too rich or too poor in nutrients, or they have inappropriate pH, salinity, or temperature [19, 24, 25]; (4) microbe-specific features, such as small non-cultivable cells, or extremely slow growers [26]. Some of these causes are interrelated and may be addressed together (see below)

Methods to increase the plate count

Objective functions

Conclusions

Findings

Methods