Lampreys are among the strangest success stories in the animal kingdom. These jawless, eel-like fish have patrolled the world’s rivers and seas for more than 400 million years, surviving at least one mass extinction, and their genomes still carry the fingerprints of the common ancestor that gave rise to every backboned animal alive today. Now, a team of researchers at Liaoning Normal University in Dalian, China, has turned to the far eastern brook lamprey, Lethenteron reissneri, to trace the evolutionary history of a family of genes with an outsized role in the nervous system, the immune system, and — intriguingly — the repair of spinal cord injuries. The study, published in the journal Immunogenetics, maps a group of transcription factors known as the PRDM family in the lamprey genome for the first time and suggests that these ancient genes may participate in both immune defense and neural regeneration.
The PRDM proteins are not household names outside of developmental biology, but they are central players in how animals build and maintain their bodies. Named for the positive regulatory domain they share, these transcription factors act as master switches that bind DNA and orchestrate the expression of other genes. Many members of the family carry a distinctive PR or SET domain that is associated with methyltransferase activity, meaning they can chemically tag histones — the protein spools around which DNA is wound — and thereby switch stretches of the genome on or off. In jawed vertebrates, PRDM proteins have been implicated in neural stem cell proliferation and differentiation, central nervous system inflammation, plasma cell development, and even cancer. Mutations in specific members have been linked to rare human conditions, including insensitivity to pain associated with PRDM12 and the developmental disorder Galloway-Mowat syndrome associated with PRDM15. Understanding when this gene family arose, and how it diversified, is therefore a question with implications far beyond evolutionary theory.
The lamprey occupies a uniquely valuable position for answering it. Lampreys and hagfish are the only living representatives of the jawless vertebrates, the sister lineage to every jawed animal from sharks to humans. Genes that are present in lampreys, in recognizable form, must have existed before the split between jawed and jawless vertebrates some 500 million years ago; genes that differ between the two lineages tell researchers what changed as the two branches went their separate evolutionary ways. Using the recently assembled chromosome-level genome of Lethenteron reissneri as their search space, the team, led by first authors Jinyang Guo and Xinyu Du under corresponding author Peng Su, systematically screened the lamprey genome for PRDM family members.
What they found was a family in a recognizably modern form. Seven PRDM genes were identified in the lamprey genome — PRDM1, PRDM4, PRDM5, PRDM8, PRDM12, PRDM14, and PRDM15 — corresponding to the seven major subfamilies that also exist in jawed vertebrates. This finding suggests that the core diversification of the PRDM family predates the last common ancestor of all living vertebrates. To place these genes in context, the researchers built a phylogenetic tree using 51 full-length PRDM protein sequences from a range of species, employing the neighbor-joining method with 1,000 bootstrap replicates to test the reliability of the branching patterns. The tree confirmed that each lamprey PRDM gene sits firmly within the clade of its corresponding vertebrate subfamily, with the lamprey sequences branching at the base of each group, exactly where an early-diverging lineage should appear.
Structural analysis reinforced the message of deep conservation. The team annotated protein domains using established bioinformatics resources and examined motif organization and predicted three-dimensional structures for each of the seven lamprey PRDM proteins. Across the board, the lamprey versions resemble their jawed-vertebrate counterparts: the characteristic N-terminal PR or SET domains, the zinc-finger arrays that mediate DNA binding, and the overall architecture of the proteins have all been preserved across hundreds of millions of years of independent evolution. Sequence alignment of the PRDM1 PR domain, for example, revealed that the key amino acid residues considered critical for methyltransferase activity are retained in the lamprey protein, hinting that the epigenetic function of this gene family was already in place in the earliest vertebrates.
But there was a twist. When the researchers performed genomic synteny analysis — comparing the arrangement of neighboring genes on chromosomes — they found that the genes flanking the lamprey PRDM loci differ significantly from those flanking the equivalent genes in jawed vertebrates. In other words, while the PRDM genes themselves have been conserved, the chromosomal neighborhoods in which they sit have been extensively reshuffled since the jawed and jawless lineages diverged. This kind of discordance between gene conservation and genome organization is exactly what one expects from a lineage as ancient as the lamprey, whose genomes are also famous for their programmed genome rearrangements and unusual chromosome evolution. The synteny results thus paint a picture of a gene family whose functions were fixed early, but whose genomic context has been freely rearranged over deep evolutionary time.
Conserved structure, however, does not by itself prove conserved function. To probe what the lamprey PRDM genes actually do, the team turned to real-time quantitative PCR, measuring expression levels of each gene under a battery of conditions. Lampreys were subjected to immune stimulations, and the researchers tracked how PRDM expression shifted in response. The data suggest that the PRDM family participates in the lamprey’s immune defense, a finding consistent with what is known about PRDM1, also known as Blimp-1, in jawed vertebrates, where it drives the differentiation of antibody-producing plasma cells and programs tissue-resident lymphocytes. The lamprey, notably, lacks adaptive immunity as it exists in jawed vertebrates — it has no immunoglobulins, no MHC molecules, and instead relies on variable lymphocyte receptors assembled from leucine-rich repeat modules. The possibility that an ancient transcription factor family contributes to immune responses in both lineages, despite their radically different immune systems, underscores how fundamental these regulatory genes are.
The most striking results came from the spinal cord injury experiments. Lampreys possess a remarkable ability that has fascinated neuroscientists for decades: after their spinal cord is severed, they can regenerate it and recover function, a feat that mammals are largely incapable of. Because of this, the lamprey has long served as a model for studying neural regeneration, with earlier work documenting the roles of guidance molecules, Wnt signaling pathways, and other conserved molecular programs in the recovery process. The Liaoning Normal University team asked whether PRDM genes join that cast. When lampreys sustained spinal cord injuries, the expression profiles of several PRDM family members changed during the repair process, indicating that these transcription factors may be involved in the injury response and regeneration. This echoes earlier findings in rats, where PRDM5 was shown to be expressed and to play an essential role after acute spinal cord injury, and where PRDM5 upregulation was associated with astrocyte proliferation and neuronal apoptosis under inflammatory conditions.
The convergence is provocative. If the same gene family helps regulate neural responses to damage in both a jawless fish and a mammal, then the molecular logic of the injury response may be far more ancient than anyone assumed. Transcription factors of the PRDM family are known in jawed vertebrates to interact with pathways such as Notch-Hes, which governs neural stem cell behavior, and to control the proliferation and differentiation of neural progenitors. The new lamprey data raise the possibility that PRDM-mediated regulation of repair programs was a feature of the ancestral vertebrate nervous system, preserved across half a billion years even as the anatomical details of regeneration diverged dramatically between lineages.
For the field of regenerative medicine, the implications are tantalizing rather than immediate. Spinal cord injuries in humans remain devastating, with limited therapeutic options and little spontaneous recovery. Researchers have long sought to understand why some animals, from lampreys to axolotls, regenerate neural tissue so effectively while mammals form inhibitory scar tissue instead. Comparative studies such as this one help narrow the search by identifying which molecular players are shared across regenerating species. If PRDM transcription factors turn out to be genuine drivers of the lamprey’s regenerative program, they could point to conserved regulatory circuits that might, in principle, be reawakened in mammalian systems. That remains a distant goal, but every conserved component identified adds a piece to the puzzle.
The study also fills a gap in the broader narrative of vertebrate gene family evolution. By confirming that seven PRDM subfamilies were already present in a jawless vertebrate, the work pushes back the timeline for the family’s expansion and demonstrates that the functional specialization seen in modern jawed vertebrates rests on foundations laid in their jawless ancestors. At the same time, the divergent synteny patterns serve as a caution against assuming that gene-by-gene comparisons capture the whole story: chromosomes themselves have histories, and in the lamprey lineage those histories have been unusually turbulent. The researchers note that the findings enrich the understanding of PRDM gene evolution and provide new clues about the roles of these genes in immune defense and spinal cord repair.
The work, funded by the National Natural Science Foundation of China and several provincial and municipal programs, is likely to spur follow-up studies using the growing toolkit of lamprey genomics, including single-cell transcriptomics that has recently been applied to these animals. As jawed vertebrate models of regeneration and immunity continue to dominate the literature, the lamprey’s ancient genome keeps offering a humbling reminder: many of the genes we consider central to modern biology were already at work before the first jaw ever evolved.
Subject of Research: Molecular evolution and functional roles of the PRDM transcription factor gene family in immune defense and spinal cord injury repair in the lamprey Lethenteron reissneri
Subject of Research: Biology
Article Title: Molecular evolution of the transcription factor PRDM genes and expression profiles in response to stimulations and spinal cord injury repair in lamprey (Lethenteron reissneri)
Article References: Guo, J., Du, X., Wu, J., Lan, B., Yang, N., & Su, P. (2025). Molecular evolution of the transcription factor PRDM genes and expression profiles in response to stimulations and spinal cord injury repair in lamprey (Lethenteron reissneri). Immunogenetics, 77(1), Article 25. https://doi.org/10.1007/s00251-025-01382-y
Image Credits: AI Generated
DOI: 10.1007/s00251-025-01382-y
Keywords: lamprey, Lethenteron reissneri, PRDM gene family, transcription factors, molecular evolution, phylogenetic analysis, genomic synteny, immune defense, spinal cord injury, neural regeneration, epigenetic regulation, vertebrate evolution
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Juliet Wilcox. (September 5, 2026). PRDM gene evolution and expression during spinal cord injury repair in lamprey. Scienmag. https://scienmag.com/prdm-gene-evolution-and-expression-during-spinal-cord-injury-repair-in-lamprey/
Juliet Wilcox. “PRDM gene evolution and expression during spinal cord injury repair in lamprey.” Scienmag, 5 September 2026, https://scienmag.com/prdm-gene-evolution-and-expression-during-spinal-cord-injury-repair-in-lamprey/. Accessed 5 September 2026.
Juliet Wilcox. “PRDM gene evolution and expression during spinal cord injury repair in lamprey.” Scienmag. September 5, 2026. https://scienmag.com/prdm-gene-evolution-and-expression-during-spinal-cord-injury-repair-in-lamprey/
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Tags: ancient gene functions in vertebratesancient gene roles in neural repairevolutionary biology of PRDM genesevolutionary genomics of PRDM genesgene expression during injury recoverygenetic basis of nerve regenerationimmune response genes in primitive vertebratesimmune response in lampreyslamprey as a model for neural repairlamprey genome analysislamprey spinal cord injury repairlong-term survival of lampreysneural regeneration in lampreysneural regeneration mechanismsPRDM gene evolutionPRDM gene family evolutionPRDM transcription factorsspinal cord injury modelsspinal cord injury repair in lampreyspinal cord regeneration mechanismstranscription factors in nervous system developmentvertebrate immune system evolutionvertebrate nervous system evolution
