The <i>wtf4</i> 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. The <i>wtf4</i> gene is a meiotic driver in <i>Schizosaccharomyces pombe</i> that uses a poison-antidote mechanism to selectively kill meiotic products (spores) that do not inherit <i>wtf4</i>. Here, we show that the Wtf4 proteins can function outside of gametogenesis and in a distantly related species, <i>Saccharomyces cerevisiae</i>. 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 <i>wtf</i> parasites can exploit protein aggregate management pathways to selectively destroy spores.