A novel transposable element-mediated mechanism causes antiviral resistance in Drosophila through truncating the Veneno protein.
Day, Jonathan P
Proc Natl Acad Sci U S A
Proceedings of the National Academy of Sciences
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Brosh, O., Fabian, D. K., Cogni, R., Tolosana, I., Day, J. P., Olivieri, F., Merckx, M., et al. (2022). A novel transposable element-mediated mechanism causes antiviral resistance in Drosophila through truncating the Veneno protein.. Proc Natl Acad Sci U S A https://doi.org/10.1073/pnas.2122026119
Hosts are continually selected to evolve new defenses against an ever-changing array of pathogens. To understand this process, we examined the genetic basis of resistance to the Drosophila A virus in Drosophila melanogaster. In a natural population, we identified a polymorphic transposable element (TE) insertion that was associated with an ∼19,000-fold reduction in viral titers, 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 titers 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.
Drosophila, Tudor domain, adaptation, transposable element, virus, Animals, DNA Transposable Elements, Dicistroviridae, Drosophila melanogaster, Gain of Function Mutation, Host-Pathogen Interactions, Sequence Deletion, Tudor Domain
Is supplemented by: https://doi.org/10.17863/CAM.84829
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.
Natural Environment Research Council (NE/P00184X/1)
Leverhulme Trust (RPG-2020-236)
External DOI: https://doi.org/10.1073/pnas.2122026119
This record's URL: https://www.repository.cam.ac.uk/handle/1810/337566
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Licence URL: http://www.rioxx.net/licenses/all-rights-reserved
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