The wtf4 meiotic driver utilizes controlled protein aggregation to generate selective cell death

Abstract

Meiotic drivers are parasitic loci that force their own transmission into greater than half of the offspring of a heterozygote. Many drivers have been identified, but their molecular mechanisms are largely unknown. Thewtf4gene is a meiotic driver inSchizosaccharomyces pombethat uses a poison-antidote mechanism to selectively kill meiotic products (spores) that do not inheritwtf4. Here, we show that the Wtf4 proteins can function outside of gametogenesis and in a distantly related species,Saccharomyces cerevisiae. The Wtf4poisonprotein forms dispersed, toxic aggregates. The Wtf4antidotecan co-assemble with the Wtf4poisonand promote its trafficking to vacuoles. We show that neutralization of the Wtf4poisonrequires both co-assembly with the Wtf4antidoteand aggregate trafficking, as mutations that disrupt either of these processes result in cell death in the presence of the Wtf4 proteins. This work reveals thatwtfparasites can exploit protein aggregate management pathways to selectively destroy spores.