Evolution of Ty1 copy number control in yeast by horizontal transfer and recombination

Transposable elements constitute a large fraction of most eukaryotic genomes. Insertion of mobile DNA sequences typically has deleterious effects on host fitness, and thus diverse mechanisms have evolved to control mobile element proliferation. Mobility of the Ty1 retrotransposon in Saccharomyces yeasts is regulated by copy number control (CNC) mediated by a self-encoded restriction factor derived from the Ty1 gag capsid gene that inhibits virus-like particle function. Here, we survey a panel of wild and human-associated strains of S. cerevisiae and S. paradoxus to investigate how genomic Ty1 content influences variation in Ty1 mobility. We observe high levels of mobility for a tester element with a gag sequence from the canonical Ty1 subfamily in permissive strains that either lack full-length Ty1 elements or only contain full-length copies of the Ty1' subfamily that have a divergent gag sequence. In contrast, low levels of canonical Ty1 mobility are observed in restrictive strains carrying full-length Ty1 elements containing a canonical gag sequence. Phylogenomic analysis of full-length Ty1 elements revealed that Ty1' is the ancestral subfamily present in wild strains of S. cerevisiae, and that canonical Ty1 in S. cerevisiae is a derived subfamily that acquired gag from S. paradoxus by horizontal transfer and recombination. Our results provide evidence that variation in the ability of S. cerevisiae and S. paradoxus strains to repress canonical Ty1 transposition via CNC is regulated by the genomic content of different Ty1 subfamilies, and that self-encoded forms of transposon control can spread across species boundaries by horizontal transfer. Author summary Mobile DNA elements dominate the genomes of many eukaryotes, although their evolutionary dynamics are often not well understood. Here, we describe how the retrovirus-like Ty1 retrotransposon diversified in Saccharomyces yeasts in the face of a potent restriction factor encoded by the Ty1 gag gene. We show that mobility of a Ty1 tester element from S. cerevisiae with a gag sequence from the "canonical" Ty1 subfamily varies substantially across diverse yeast strains. Strains with full-length Ty1 elements carrying a canonical gag sequence in their genomes restrict tester Ty1 mobility while strains containing only elements from the Ty1' subfamily do not, suggesting functional divergence among Ty1 subfamilies. Permissive strains lacking Ty1 elements with canonical gag can be converted to restrictive strains by introducing Ty1 elements with canonical gag into permissive genomes. Phylogenetic analyses show that Ty1' is the ancestral subfamily in wild S. cerevisiae lineages, whereas canonical Ty1 is a derived subfamily found only in human-associated strains. Furthermore, the canonical Ty1 gag arose by recombination between an ancestral Ty1' element and a Ty1 element horizontally transferred from S. paradoxus. Our results highlight how exchange of retrotransposon sequences across species can impact the repertoire and mobility of mobile DNA elements in eukaryotic genomes.