Jumping Genes May Shape Fish Immunity, New Analysis Reveals

Deep inside the genomes of every bony fish, from gilthead seabream to zebrafish, stretches a landscape of mobile DNA sequences that have been quietly rewriting the genetic code for hundreds of millions of years. These sequences, known as transposable elements, are repetitive DNA units that can copy and paste themselves to new genomic locations, reshuffling chromosomes and occasionally donating novel functions to the genes they colonize. A new systematic review and computational analysis published in Heredity by Jose Carlos Campos-Sánchez and Maria del Mar Ortega-Villaizan of Universidad Miguel Hernández in Spain now suggests that this ancient genomic traffic is far from random with respect to immunity. The study reveals that transposable element sequences match immune-related genes in teleost fish with striking frequency, and that these associations are significantly enriched across most of the species examined.

Transposable elements constitute a major component of vertebrate genomes. In humans they occupy nearly half of the DNA, and in fish the fraction can be similarly substantial, varying widely among lineages. For decades these repeats were dismissed as junk DNA, but modern genomics has recast them as major players in evolution. By inserting into new sites and promoting recombination between repeat copies, they can drive gene innovation and chromosomal rearrangements. Yet this creative capacity carries a cost. Unrestrained transposable element activity can compromise genomic integrity, and in mammals persistent activation of these elements has been linked to inflammatory and carcinogenic pathways, including chronic inflammation, cancer progression and autoimmune disease. The vertebrate body therefore deploys two key restraining mechanisms: epigenetic control, which chemically silences the repeats, and immune surveillance, which detects their transcripts as molecular signatures of danger.

Teleost fish, the most diverse group of bony vertebrates, represent an early vertebrate lineage in which the immune architecture is largely conserved relative to mammals. They possess inflammatory molecules, cell-surface and signalling receptors, and antiviral genes that mirror their mammalian counterparts. What has remained largely unexplored until now is the relationship between the mobile DNA fraction of fish genomes and this immune machinery. Fish transposable elements have been catalogued in individual species, and databases such as FishTEDB now consolidate consensus sequences, but a systematic interrogation of their overlap with immune genes across the ray-finned fishes had never been attempted on this scale.

To close that gap, the researchers combined a PRISMA-based systematic literature review with an extensive BLASTn screening. They took transposable element consensus sequences from FishTEDB and searched them against GenBank entries for Actinopterygii, the ray-finned fishes, looking for sequence matches that landed within immune-related loci. The computational strategy was complemented by EggNOG annotation and enrichment analysis, which assigns genes to orthologous groups and functional categories, allowing the team to test whether transposable element-gene associations were overrepresented in immune-related functional classes rather than distributed randomly across the genome.

The results were unambiguous. The screening revealed frequent transposable element sequence matches to immune-related loci across teleost species, touching inflammatory molecules, cell-surface and signalling receptors, and antiviral genes. The EggNOG functional profiling, performed across eight teleost species, supported a recurrent association between transposable element sequences and immune-related annotations. Most tellingly, the enrichment analysis found significant enrichment of immune-related transposable element-gene associations in six of the eight species analysed. In other words, in the majority of the fish genomes examined, the mobile DNA sequences were not scattered uniformly across all gene classes but clustered disproportionately around genes that the immune system uses.

The biological significance of this clustering remains an open question, and the authors are careful to frame it as such. Transposable element insertions near immune genes could be functionally neutral, a by-product of how repeats accumulate in certain chromosomal contexts. Alternatively, they could reflect genuine regulatory interplay. In mammals, transposable element-derived sequences have been domesticated as regulatory elements that instruct the immune system, contributing promoters and enhancers to interferon genes and other immune loci. The new review situates fish within this broader vertebrate picture, discussing the possible regulatory mechanisms by which fish transposable elements might influence immune gene expression, and the epigenetic context, including DNA methylation, that normally keeps their activity in check.

Experimental evidence from fish models already hints that this interplay is real. In zebrafish embryos, loss of DNA methylation activates retrotransposons and triggers antiviral signalling, a phenomenon known as viral mimicry, in which the cell responds to derepressed endogenous repeats as if they were invading pathogens. Similar viral mimicry responses have been documented in mammalian cancer cells treated with DNA-demethylating agents. In the gilthead seabream, carrageenin-induced inflammation has been shown to modulate transposable element expression in skin and brain tissue, directly linking an inflammatory stimulus to mobile element activity in a farmed fish species. Environmental factors also matter: retrotransposon methylation and activity in wild European eels vary with body size, and the Rex3 retroelement in teleosts shows an intriguing relationship with environmental temperature.

The review also maps the diversity of transposable elements in fish genomes, which spans retrotransposons, DNA transposons and endogenous retroviruses, some of which are relics of past infections that have been repurposed as evolutionary innovations. Fish genomes have repeatedly captured and mobilized host genes through elements such as Helitron transposons, and piggyBac-like transposons have been found fused with herpesviruses in teleosts, illustrating the porous boundary between mobile elements and viral genomes. Horizontal transfer of transposons between vertebrate lineages adds another layer of dynamism to this genomic ecosystem, meaning that the mobile DNA repertoire of any fish species is shaped not only by vertical inheritance but also by cross-species invasion.

Looking forward, the authors outline future directions that integrate transposable element annotation with genomic mapping, epigenetic analyses, transposable element transcription and immune gene expression. Such integrative approaches would clarify whether the observed transposable element-immune associations have regulatory consequences for fish health, disease resistance and stress responses. The stakes extend beyond basic biology. Aquaculture is a rapidly growing food sector in which immune regulation, welfare and disease control are central concerns, and farmed fish face inflammatory challenges from pathogens, parasites and environmental stressors. If transposable elements turn out to be embedded in the regulatory architecture of fish immune genes, they could become targets for selective breeding, epigenetic intervention or genome editing aimed at improving disease resistance in farmed species.

Overall, the study provides a comprehensive perspective on the intricate relationship between transposable elements, epigenetic regulation and immune system dynamics in teleost fish, and argues for their inclusion in future studies of fish immune regulation, health and aquaculture. What was once dismissed as genomic junk is emerging, in fish as in mammals, as a potential instructor of the immune system, and the bony fishes, with their conserved immune architecture and rich mobile element diversity, now offer a comparative vantage point from which the deep evolutionary history of this genomic dialogue can finally be read.

Subject of Research: Genetics

Article Title: Transposable elements, immune-related genes and epigenetic context in teleost fish: insights from a systematic review and in silico analysis

Article References: Campos-Sánchez, J. C., & Ortega-Villaizan, M. D. M. (2026). Transposable elements, immune-related genes and epigenetic context in teleost fish: insights from a systematic review and in silico analysis. Heredity. https://doi.org/10.1038/s41437-026-00893-y

Image Credits: AI Generated

DOI: 10.1038/s41437-026-00893-y

Keywords: transposable elements, teleost fish, immune system, epigenetics, genomics, aquaculture, viral mimicry, Heredity, Transposable, elements, immune-related, genes