Meiotic null MSH2 and SGS1 alleles in S. cerevisiae x S. uvarum hybrids result in near-haploid offspring with mixed parental chromosomal inheritance
- 1Department of Genome Sciences, University of Washington, Seattle, WA, USA
Abstract
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 the Saccharomyces clade, including the model organism Saccharomyces cerevisiae. Members of Saccharomyces intermate 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 parent Saccharomyces species—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 of S. cerevisiae and its sister species S. paradoxus but leads to increased mutation accumulation during normal mitotic growth. To overcome this drawback, conditional alleles that specifically repress expression of mismatch repair machinery and the RecQ helicase SGS1—a major regulator of mitotic and meiotic recombination—during meiosis have been applied in S. cerevisiae x S. paradoxus hybrids with success. Here, we describe the application of the meiotic null system to a different hybrid: S. cerevisiae x S. 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. S. uvarum chromosomes which have undergone translocations since S. cerevisiae divergence were found to be co-inherited in viable progeny. Strikingly, these viable near-haploid hybrid offspring predominantly inherited Chr XII—carrying the critical rDNA repeat array—from the S. uvarum parent. These populations of mixed hybrid genomes can be leveraged in phenotypic studies to further understand the effects of hybrid genomes on organismal fitness.
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BibTeX
@misc{wang2026meiotic,
title = {{Meiotic null MSH2 and SGS1 alleles in S. cerevisiae x S. uvarum hybrids result in near-haploid offspring with mixed parental chromosomal inheritance}},
author = {Taylor K. Wang and Maitreya J. Dunham},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.1101/2025.06.02.657486},
url = {https://doi.org/10.1101/2025.06.02.657486},
note = {CC BY-NC 4.0},
}
RIS
TY - UNPB
TI - Meiotic null MSH2 and SGS1 alleles in S. cerevisiae x S. uvarum hybrids result in near-haploid offspring with mixed parental chromosomal inheritance
AU - Taylor K. Wang
AU - Maitreya J. Dunham
PY - 2026
DA - 2026/10/29
PB - bioRxiv
DO - 10.1101/2025.06.02.657486
UR - https://doi.org/10.1101/2025.06.02.657486
AB - 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 the Saccharomyces clade, including the model organism Saccharomyces cerevisiae. Members of Saccharomyces intermate 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 parent Saccharomyces species—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 of S. cerevisiae and its sister species S. paradoxus but leads to increased mutation accumulation during normal mitotic growth. To overcome this drawback, conditional alleles that specifically repress expression of mismatch repair machinery and the RecQ helicase SGS1—a major regulator of mitotic and meiotic recombination—during meiosis have been applied in S. cerevisiae x S. paradoxus hybrids with success. Here, we describe the application of the meiotic null system to a different hybrid: S. cerevisiae x S. 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. S. uvarum chromosomes which have undergone translocations since S. cerevisiae divergence were found to be co-inherited in viable progeny. Strikingly, these viable near-haploid hybrid offspring predominantly inherited Chr XII—carrying the critical rDNA repeat array—from the S. uvarum parent. These populations of mixed hybrid genomes can be leveraged in phenotypic studies to further understand the effects of hybrid genomes on organismal fitness.
SN - 2692-8205
ER -