Evolution of a restriction factor by domestication of a yeast retrotransposon.

Transposable elements (TEs) drive genome evolution in all branches of life. TE insertions are often deleterious to their hosts and necessitate evolution of control mechanisms to limit their spread. The long terminal repeat retrotransposon Ty1 prime (Ty1'), a subfamily of the Ty1 family, is present in many Saccharomyces cerevisiae strains but little is known about what controls its copy number. Here, we provide evidence that a novel gene from an exapted Ty1' sequence, Domesticated Restriction of Ty1' relic 2 (DRT2), encodes a restriction factor that inhibits Ty1' movement. DRT2 arose through domestication of a Ty1' GAG gene and contains the C-terminal domain of capsid (CA-CTD), which in the related Ty1 canonical (Ty1c) subfamily functions as a self-encoded restriction factor. Bioinformatic analysis reveals the widespread nature of DRT2, its evolutionary history, and pronounced structural variation at the Ty1' relic 2 locus. Ty1' retromobility analyses demonstrate DRT2 restriction factor functionality, and northern blot and RNA-seq analysis indicate that DRT2 is transcribed in multiple strains. Velocity co-sedimentation profiles indicate an association between Drt2 and Ty1' virus like particles (VLPs) or assembly complexes. Chimeric Ty1' elements containing DRT2 retain retromobility, suggesting an ancestral role of productive Gag CA-CTD functionality is present in the sequence. Unlike Ty1c, Ty1' retromobility increases with copy number, suggesting that CA-CTD based restriction is not limited to the Ty1c subfamily self-encoded restriction factor and drove the endogenization of DRT2. The discovery of an exapted Ty1' restriction factor provides insight into the evolution of the Ty1 family, evolutionary hot-spots, and host-TE interactions.