The  wtf4  meiotic driver utilizes controlled protein aggregation to generate selective cell death.
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. The  wtf4  gene is a meiotic driver in  Schizosaccharomyces pombe  that uses a poison-antidote mechanism to selectively kill meiotic products (spores) that do not inherit  wtf4 . Here, we show that the Wtf4 proteins can function outside of gametogenesis and in a distantly related species,  Saccharomyces cerevisiae . The Wtf4 poison  protein forms dispersed, toxic aggregates. The Wtf4 antidote  can co-assemble with the Wtf4 poison  and promote its trafficking to vacuoles. We show that neutralization of the Wtf4 poison  requires both co-assembly with the Wtf4 antidote  and aggregate trafficking, as mutations that disrupt either of these processes result in cell death in the presence of the Wtf4 proteins. This work reveals that  wtf  parasites can exploit protein aggregate management pathways to selectively destroy spores.
Nuckolls NL, Mok AC, Lange JJ, Yi K, Kandola TS, Hunn AM, McCroskey S, Snyder JL, Bravo Núñez MA, McClain M, McKinney SA, Wood C, Halfmann R, Zanders SE