Thewtf4meiotic driver utilizes controlled protein aggregation to generate selective cell death

Abstract

AbstractMeiotic 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. 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 similar Wtf4antidoteprotein also forms aggregates but is sequestered within or near vacuoles and is mostly benign. 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 sequestration, as mutations that disrupt either of these processes results in cell death. This work reveals thatwtfparasites can exploit protein aggregate management pathways to selectively destroy gametes.