Gag proteins encoded by endogenous retroviruses are required for zebrafish development
Open accessPublished version of a preprint
Abstract
Transposable elements (TEs) make up the bulk of eukaryotic genomes and examples abound of TE-derived sequences repurposed for organismal function. The process by which TEs become coopted remains obscure because most cases involve ancient, transpositionally inactive elements. Reports of active TEs serving beneficial functions are scarce and often contentious due to difficulties in manipulating repetitive sequences. Here, we show that recently active TEs in zebrafish encode products critical for embryonic development. Knockdown and rescue experiments demonstrate that the endogenous retrovirus family BHIKHARI-1 (Bik-1) encodes a Gag protein essential for mesoderm development. Mechanistically, Bik-1 Gag associates with the cell membrane, and its ectopic expression in chicken embryos alters cell migration. Similarly, depletion of BHIKHARI-2 Gag, a relative of Bik-1, causes defects in neural crest development in zebrafish. We propose an “addiction” model to explain how active TEs can be integrated into conserved developmental processes.
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Cites
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- Authors
- Chang, N.-C., Wells, J. N., Wang, A. Y., Schofield, P., Huang, Y.-C., Truong, V. H., Simoes-Costa, M., & Feschotte, C.
- Affiliations
- Cornell University (US)
- Boston Children's Hospital (US)
- Department of Systems Biology, Harvard Medical School
- Corresponding author
- Chang, Ni-Chen
- Wells, Jonathan N.
- Feschotte, Cédric
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2025-04-28
- Volume
- 122
- Issue
- 18
- Pages
- e2411446122-e2411446122
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC12067270
- OpenAlex
- W4409872540
- Cited by
- 27
- References
- 7
- Citations by year
- 2026: 12 · 2025: 14 · 2024: 1
- FWCI
- 14.05
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed Central (submittedVersion, cc-by)
- Funders
- Human Frontier Science Program (LT000017/2019-L)
- HHS | NIH (R35-GM122550)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
- Keywords
- endogenous retroviruses, Gag protein, transposable elements, mesoderm formation, neural crest development, cell migration, cell membrane association, zebrafish embryonic development, addiction models
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