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 Wtf4poison protein forms dispersed, toxic aggregates. The Wtf4antidote can co-assemble with the Wtf4poison and promote its trafficking to vacuoles. We show that neutralization of the Wtf4poison requires both co-assembly with the Wtf4antidote 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.

Meiotic drivers bias gametogenesis to ensure their transmission into more than half the offspring of a heterozygote. In Schizosaccharomyces pombe, wtf meiotic drivers destroy the meiotic products (spores) that do not inherit the driver from a heterozygote, thereby reducing fertility. wtf drivers encode both a Wtfpoison protein and a Wtfantidote protein using alternative transcriptional start sites. Here, we analyze how the expression and localization of the Wtf proteins are regulated to achieve drive. We show that transcriptional timing and selective protein exclusion from developing spores ensure that all spores are exposed to Wtf4poison, but only the spores that inherit wtf4 receive a dose of Wtf4antidote sufficient for survival. In addition, we show that the Mei4 transcription factor, a master regulator of meiosis, controls the expression of the wtf4poison transcript. This transcriptional regulation, which includes the use of a critical meiotic transcription factor, likely complicates the universal suppression of wtf genes without concomitantly disrupting spore viability. We propose that these features contribute to the evolutionary success of the wtf drivers.

30Meiotic drivers are parasitic loci that force their own transmission into greater than half of the 31 offspring of a heterozygote. Many drivers have been identified, but their molecular mechanisms 32 are largely unknown. The wtf4 gene is a meiotic driver in Schizosaccharomyces pombe that 33 uses a poison-antidote mechanism. Here, we show that the Wtf4 proteins can function outside 34 of gametogenesis and in a distantly related species, Saccharomyces cerevisiae. The Wtf4 poison 35 protein forms dispersed, toxic aggregates. The similar Wtf4 antidote protein also forms aggregates 36 but is sequestered within or near vacuoles and is mostly benign. The Wtf4 antidote can co-37 assemble with the Wtf4 poison and promote its trafficking to vacuoles. We show that neutralization 38 of the Wtf4 poison requires both co-assembly with the Wtf4 antidote and aggregate sequestration, as 39 mutations that disrupt either of these processes results in cell death. This work reveals that wtf 40 parasites can exploit protein aggregate management pathways to selectively destroy gametes.

No abstract