Discovery of a Genetic Toxin-Antidote System in Vertebrates

Toxin-antidote (TA) systems are selfish genetic elements that bias their own inheritance by coupling a toxin that kills daughter cells or offspring with an antidote that specifically rescues those with the TA. TAs are a widespread phenomenon, observed in bacteria, fungi, plants, and invertebrate animals, but have not yet been described in vertebrates. Here we report the first known vertebrate TA system that sabotages mammalian embryogenesis. The HSR locus on mouse chromosome 1 is a selfish genetic element that biases its transmission through the female germline. When HSR heterozygous females are crossed with wild-type males, wild-type embryos show high mortality, leading to preferential survival of embryos with HSR. The mechanism underlying embryo killing was unknown. We find that HSR kills wild-type post-implantation embryos by depositing a toxin (SP100) that induces significant DNA damage. Embryos with HSR also inherit the toxin but survive by expressing an antidote (SP110) that blocks the toxins effects. Our findings reveal a previously unrecognized genetic cheating strategy in vertebrates and demonstrate its impact on mammalian reproduction.