“Meiotic null MSH2 and SGS1 alleles in S. cerevisiae x S. uvarum hybrids result in near-haploid offspring with mixed parental chromosomal inheritance.”

In the natural world, genetic isolation between closely related species is often maintained by direct F1 hybrid sterility or hybrid breakdown in subsequent generations. This phenomenon is also observed in microorganisms within species of theSaccharomycesclade, including the model organismSaccharomyces cerevisiae. Members ofSaccharomycesintermate and historical hybridization events have left genomic footprints, but these hybrids are themselves sterile and produce very few viable offspring. Previous work suggests a main cause of F1 hybrid sterility is the action of mismatch repair machinery. The sequence divergence between two parentSaccharomycesspecies—from ∼10% to ∼20%—is recognized by the cell as an aberrant attempt to recombine nonhomologous chromosomes during meiosis I, leading to massive nondisjunction and aneuploidy. Deletion of mismatch repair machinery improves fertility in hybrids ofS. cerevisiaeand its sister speciesS. paradoxusbut leads to increased mutation accumulation during normal mitotic growth. To overcome this drawback, conditional alleles that specifically repress expression of mismatch repair machinery during meiosis have been applied inS. cerevisiaexS. paradoxushybrids with success. Here, we describe the application of the meiotic null system to a different hybrid:S. cerevisiaexS. uvarum. The system does not increase hybrid fertility likely due to increased sequence divergence and chromosomal translocations, but mass spore recovery and flow cytometry enable the recovery of near-haploid offspring which inherit an assortment of parental chromosomes. These populations of mixed hybrid genomes can be leveraged in phenotypic studies to further understand the effects of hybrid genomes on organismal fitness.