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Holostean genomes reveal evolutionary novelty in the vertebrate immunoproteasome that have implications for MHCI function

Title: Holostean genomes reveal evolutionary novelty in the vertebrate immunoproteasome that have implications for MHCI function
Authors: Barker, Andi V; Carlson, Kara B; Wcisel, Dustin J; Birchler De Allende, Ian; Braasch, Ingo; Fisk, Michael; Dornburg, Alex; Yoder, Jeffrey A
Contributors: Malik, Harmit; National Science Foundation; Triangle Center for Evolutionary Medicine; National Evolutionary Synthesis Center; National Institute of General Medical Sciences; National Institutes of Health
Source: Molecular Biology and Evolution ; volume 43, issue 3 ; ISSN 0737-4038 1537-1719
Publisher Information: Oxford University Press (OUP)
Publication Year: 2026
Description: Holosteans (gars and bowfins) have emerged as valuable models for understanding early vertebrate evolution, offering insights into diverse topics ranging from genomic architecture to molecular processes. These lineages also exhibit unusual features in their immune response, combining molecular elements seen in both tetrapods and ray-finned fishes. However, the immune repertoire of holosteans remains relatively unexplored. Here, we investigate the evolution of PSMB8, a core component of the immunoproteasome responsible for cleaving intracellular proteins into peptides for presentation by MHC class I molecules. We identify two holostean PSMB8 types—S type and K type—that are unique among vertebrates. These types likely cause significant biochemical changes to the S1 binding pocket involved in antigen cleavage which could result in the presentation of novel peptides by MHC class I. Integrating comparative analyses across major ray-finned fish lineages demonstrates that bowfins and gars independently evolved the PSMB8 S type within separate PSMB8 paralog lineages, while the PSMB8-K type is an evolutionary novelty found only in gars. Our results provide new perspectives into PSMB8 haplotypes and their role in peptide antigen processing, offering unique insights into the molecular evolution of the vertebrate immunity and antigen presentation.
Document Type: article in journal/newspaper
Language: English
DOI: 10.1093/molbev/msag030
DOI: 10.1093/molbev/msag030/66712777/msag030.pdf
Availability: https://doi.org/10.1093/molbev/msag030; https://academic.oup.com/mbe/advance-article-pdf/doi/10.1093/molbev/msag030/66712777/msag030.pdf; https://academic.oup.com/mbe/article-pdf/43/3/msag030/66712777/msag030.pdf
Rights: https://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.74C9F6C9
Database: BASE