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1. Target-enriched long-read sequencing (TELSeq) contextualizes antimicrobial resistance genes in metagenomes

   https://doi.org/10.1186/s40168-022-01368-y  

   Slizovskiy, Ilya B.; Oliva, Marco; Settle, Jonathen K.; Zyskina, Lidiya V.; Prosperi, Mattia; Boucher, Christina; Noyes, Noelle R. (December 2022, Microbiome)

   Abstract Background Metagenomic data can be used to profile high-importance genes within microbiomes. However, current metagenomic workflows produce data that suffer from low sensitivity and an inability to accurately reconstruct partial or full genomes, particularly those in low abundance. These limitations preclude colocalization analysis, i.e., characterizing the genomic context of genes and functions within a metagenomic sample. Genomic context is especially crucial for functions associated with horizontal gene transfer (HGT) via mobile genetic elements (MGEs), for example antimicrobial resistance (AMR). To overcome this current limitation of metagenomics, we present a method for comprehensive and accurate reconstruction of antimicrobial resistance genes (ARGs) and MGEs from metagenomic DNA, termed t arget- e nriched l ong-read seq uencing (TELSeq). Results Using technical replicates of diverse sample types, we compared TELSeq performance to that of non-enriched PacBio and short-read Illumina sequencing. TELSeq achieved much higher ARG recovery (>1,000-fold) and sensitivity than the other methods across diverse metagenomes, revealing an extensive resistome profile comprising many low-abundance ARGs, including some with public health importance. Using the long reads generated by TELSeq, we identified numerous MGEs and cargo genes flanking the low-abundance ARGs, indicating that these ARGs could be transferred across bacterial taxa via HGT. Conclusions TELSeq can provide a nuanced view of the genomic context of microbial resistomes and thus has wide-ranging applications in public, animal, and human health, as well as environmental surveillance and monitoring of AMR. Thus, this technique represents a fundamental advancement for microbiome research and application. 

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2. Examining horizontal gene transfer in microbial communities

   https://doi.org/10.1038/ s41579-021-00534-7  

   Brito, I (April 2021, Nature reviews)

   null (Ed.)

   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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3. The ecology of horizontal gene transfer

   https://doi.org/10.1016/j.tig.2026.02.002  

   Van_Etten, Julia; Johnson, Matthew D (June 2026, Trends in Genetics)

   Horizontal gene transfer (HGT) generates genetic variation in populations across all domains of life; however, most studies focus on individual transfers and functional information derived therefrom. This is useful but does not consider DNA transfer more broadly, that is, nongene transfers, donor–recipient dynamics, or trends and background levels that may help infer ecological information. Here, we review the mechanistic underpinnings of DNA transfer, literature from diverse fields that addresses HGT on a community basis and the associated methodological challenges, and propose a framework for conceptualizing the process of DNA transfer, highlighting DNA mobility as a feature of community ecology and DNA itself as a public good. These ideas coalesce to support DNA transfer as a fundamental ecological phenomenon that remains largely unmeasured. 

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4. Beyond adaptive gene transfers: a primer on horizontal gene transfer across scales

   https://doi.org/10.1093/icb/icag125  

   Van_Etten, Julia; Johnson, Matthew D (July 2026, Integrative And Comparative Biology)

   Abstract Horizontal gene transfer (HGT) is a fundamental ecological and evolutionary process involving the movement of genetic material across taxa within a single generation. While traditionally studied at the level of individual genes with encoded adaptive functions, recent advances in genomics and metagenomics highlight the need for a broader, integrative framework. Here, we expand the concept of the “ecology of DNA transfer,” which conceptualizes HGT as a multi-layered process spanning the genome, cell, and ecological context. We further explore how the fate and expression of transferred DNA vary over evolutionary timescales, from recently acquired, transcriptionally silenced sequences to ancient, fully integrated genes. Together, this framework underscores HGT as a dynamic, context-dependent process shaped by interactions across biological scales. 

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5. Beyond Agrobacterium-Mediated Transformation: Horizontal Gene Transfer from Bacteria to Eukaryotes

   Lacroix, Benoit; Citovsky, Vitaly. (January 2018, Current topics in microbiology and immunology)

   Besides the massive gene transfer from organelles to the nuclear genomes, which occurred during the early evolution of eukaryote lineages, the importance of horizontal gene transfer (HGT) in eukaryotes remains controversial. Yet, increasing amounts of genomic data reveal many cases of bacterium-to-eukaryote HGT that likely represent a significant force in adaptive evolution of eukaryotic species. However, DNA transfer involved in genetic transformation of plants by Agrobacterium species has traditionally been considered as the unique example of natural DNA transfer and integration into eukaryotic genomes. Recent discoveries indicate that the repertoire of donor bacterial species and of recipient eukaryotic hosts potentially are much wider than previously thought, including donor bacterial species, such as plant symbiotic nitrogen-fixing bacteria (e.g., Rhizobium etli) and animal bacterial pathogens (e.g., Bartonella henselae, Helicobacter pylori), and recipient species from virtually all eukaryotic clades. Here, we review the molecular pathways and potential mechanisms of these trans-kingdom HGT events and discuss their utilization in biotechnology and research. 

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