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Examining horizontal gene transfer in microbial communities


Bacteria acquire novel DNA through horizontal gene transfer (HGT), a process that enables an organism to rapidly adapt to changing environmental conditions, provides a competitive edge and potentially alters its relationship with its host. Although the HGT process is routinely exploited in laboratories, there is a surprising disconnect between what we know from laboratory experiments and what we know from natural environments, such as the human gut microbiome. Owing to a suite of newly available computational algorithms and experimental approaches, we have a broader understanding of the genes that are being transferred and are starting to understand the ecology of HGT in natural microbial communities. This Review focuses on these new technologies, the questions they can address and their limitations. As these methods are applied more broadly, we are beginning to recognize the full extent of HGT possible within a microbiome and the punctuated dynamics of HGT, specifically in response to external stimuli. Furthermore, we are better characterizing the complex selective pressures on mobile genetic elements and the mechanisms by which they interact with the bacterial host genome.

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Fig. 1: General routes of horizontal gene transfer within natural communities.
Fig. 2: Metagenomic assessment of the mobilome.
Fig. 3: Reporter constructs for examining recipients of horizontal gene transfer and movement of mobile genetic elements.
Fig. 4: Hi-C applications to identify bacterial host associations of mobile genetic elements.
Fig. 5: PCR-based methods for examining single mobile genes and their genomic contexts.
Fig. 6: Disentangling the processes of horizontal gene transfer and natural selection.


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The author is a Packard Fellow of Science and Engineering, a Pew Biomedical Scholar and a Sloan Foundation Research Fellow. This research was funded by the Sloan Foundation Microbes in the Built Environment programme (2018-11009), the US National Sciences Foundation (ABI 1661338, EAGER 1650122), the US National Institutes of Health (1DP2HL141007), the US Department of Agriculture (BRAG:2017-03796) and the Bill & Melinda Gates Grand Challenges Program (OPP1161064). The author thanks members of the Brito laboratory for comments on the manuscript.

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Nature Reviews Microbiology thanks H. Wang and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Mobile genetic elements

(MGEs). Units of DNA that can be transferred within a genome or between genomes.


The evolution of a clade of organisms that are genetically and often ecologically distinct from neighbouring clades.


Chemicals that can elicit changes in the DNA, including but not limited to strand breakage, deamination and cross-linking, which can lead to mutation.


The organization of unicellular organisms, often multiple species, into an adherent, cohesive mat, often involving extracellular polymeric substances and distinct changes in function compared with planktonic cells.

k-mer composition

A tally of the unique DNA fragments k base pairs long in a genome or a dataset of sequencing reads or contigs.


Phage genomes that are integrated and replicated along within the genome of their host. These are either phages in their lysogenic phase or they are inactive (mutated so they no longer can enter a lytic phase).

Lytic phages

Phages that reproduce within a cell and subsequently lyse the cell to release the virions.


The study of bacterial cell culture using high-throughput methods, usually with the goal of isolating diverse organisms from complex microbial communities.


Small DNA fragments found within CRISPR arrays that are derived from invading mobile genetic DNA (plasmids or phages).

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Brito, I.L. Examining horizontal gene transfer in microbial communities. Nat Rev Microbiol 19, 442–453 (2021).

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