Selfish genetic elements persist in species despite their negative impacts on host fitness. Toxin-antidote selfish elements kill progeny that do not inherit the genetic element thus increasing their representation in the next generation. The
peel-1/zeel-1 gene pair is a toxin-antidote system responsible for a hybrid incompatibility between C. elegans Bristol N2 and Hawaiian CB4856 strains. PEEL-1 is a sperm-delivered toxin that arrests embryonic development. However, embryos inheriting the
zeel-1 antidote gene can escape PEEL-1 toxicity. We are investigating the molecular mechanism of PEEL-1 toxicity and ZEEL-1 anti-toxicity. We used a forward genetic screen to discover that the small, conserved protein, F47B7.1 is necessary for PEEL-1 toxicity. Expression of PEEL-1 and F47B7.1 together induces cell swelling and cell death in HEK293T mammalian cells. ZEEL-1 expression suppresses this toxicity. Therefore, I have reconstituted the toxin and antidote activity in a heterologous system, suggesting that we have identified the minimal set of proteins involved in toxicity and anti-toxicity. My continued work uses C. elegans, HEK293T cells, and in vitro biochemistry to dissect the molecular mechanism of toxicity and anti-toxicity.