A novel transposable element-mediated mechanism causes antiviral resistance in Drosophila through truncating the Veneno protein
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Authors
Brosh, Osama
Fabian, Daniel K
Cogni, Rodrigo
Tolosana, Ignacio
Day, Jonathan P
Olivieri, Francesca
Merkx, Manon
Akilli, Nazli
Szkuta, Piotr
Journal Title
Proceedings of the National Academy of Sciences of USA
ISSN
0027-8424
Publisher
National Academy of Sciences
Type
Article
This Version
AM
Metadata
Show full item recordCitation
Brosh, O., Fabian, D. K., Cogni, R., Tolosana, I., Day, J. P., Olivieri, F., Merkx, M., et al. A novel transposable element-mediated mechanism causes antiviral resistance in Drosophila through truncating the Veneno protein. Proceedings of the National Academy of Sciences of USA https://doi.org/10.17863/CAM.84975
Abstract
Hosts are continually selected to evolve new defences against an ever-changing array of pathogens. To understand this process, we examined the genetic basis of resistance to the virus DAV in Drosophila melanogaster. In a natural population, we identified a polymorphic transposable element (TE) insertion that was associated with a ~19,000-fold reduction in viral titres, allowing flies to largely escape the harmful effects of infection by this virulent pathogen. The insertion occurs in the protein-coding sequence of the gene Veneno, which encodes a Tudor domain protein. By mutating Veneno with CRISPR-Cas9 in flies and expressing it in cultured cells, we show that the ancestral allele of the gene has no effect on viral replication. Instead, the TE insertion is a gain-of-function mutation that creates a gene encoding a novel resistance factor. Viral titres remained reduced when we deleted the TE sequence from the transcript, indicating that resistance results from the TE truncating the Veneno protein. This is a novel mechanism of virus resistance and a new way by which TEs can contribute to adaptation.
Sponsorship
This work was funded by grants from the Natural Environment Research Council (NE/P00184X/1) and the Leverhulme Trust (RPG-2020-236) to FJ. RC is funded by the São Paulo Research Foundation (FAPESP) (2013/25991-0 and 2015/08307-3), the National Council for Scientific and Technological Development (CNPq) (307447/2018-9) and a Newton Advanced Fellowship from the Royal Society (NAF\R1\180244). OB is funded by the Dr. Herchel Smith Fellowship.
Funder references
Natural Environment Research Council (NE/P00184X/1)
Leverhulme Trust (RPG-2020-236)
Embargo Lift Date
2025-05-27
Identifiers
This record's DOI: https://doi.org/10.17863/CAM.84975
This record's URL: https://www.repository.cam.ac.uk/handle/1810/337566
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