A Defective Meiotic Outcome of a Failure in Homologous Pairing and Synapsis Is Masked by Meiotic Quality Control

Successful gamete production is ensured by meiotic quality control, a process in which germ cells that fail in bivalent chromosome formation are eliminated during meiotic prophase. To date, numerous meiotic mutants have been isolated in a variety of model organisms, using defects associated with a failure in bivalent formation as hallmarks of the mutant. Presumably, the meiotic quality control mechanism in those mutants is overwhelmed. In these mutants, all germ cells fail in bivalent formation, and a subset of cells seem to survive the elimination process and develop into gametes. It is possible that mutants that are partially defective in bivalent formation were missed in past genetic screens, because no evident meiotic defects associated with failure in bivalent formation would have been detectable. Meiotic quality control effectively eliminates most failed germ cells, leaving predominately successful ones. Here, we provide evidence supporting this possibility. The Caenorhabditis elegans mrg-1 loss-of-function mutant does not appear to be defective in bivalent formation in diakinesis oocytes. However, defects in homologous chromosome pairing and synapsis during the preceding meiotic prophase, prerequisites for successful bivalent formation, were observed in most, but not all, germ cells. Failed bivalent formation in the oocytes became evident once meiotic quality control was abrogated in the mrg-1 mutant. Both double-strand break repair and synapsis checkpoints are partly responsible for eliminating failed germ cells in the mrg-1 mutant. Interestingly, removal of both checkpoint activities from the mrg-1 mutant is not sufficient to completely suppress the increased germline apoptosis, suggesting the presence of a novel meiotic checkpoint mechanism.