A novel transposable element-mediated mechanism causes antiviral resistance in Drosophila through truncating the Veneno protein

Author(s)

Brosh, Osama ; Fabian, Daniel K. ; Cogni, Rodrigo ; Tolosana, Ignacio ; Day, Jonathan P. ; Olivieri, Francesca ; Merckx, Manon ; Akilli, Nazli ; Szkuta, Piotr ; Jiggins, Francis M.

• Document type: Journal article
• Source: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA; v. 119, n. 29, p. 10-pg., 2022-07-19.

Abstract

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 similar to 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. (AU)

• FAPESP's process: 13/25991-0 - Ecological genomics of insects: climate adaptations and evolution of ecological interactions
• Grantee: Rodrigo Cogni
• Support Opportunities: Research Grants - Young Investigators Grants