A largely shared genetic architecture underlies Saccharomyces cerevisiae persistence across different mouse host genotypes
- 1University of Southern California
Abstract
The extent to which interactions between microbial and host genotypes shape opportunistic pathogen persistence within hosts is an important open question. To assess the contribution of these interactions to persistence, we used Saccharomyces cerevisiae, a genetically tractable model for studying opportunistic fungal persistence in mammalian hosts. A pooled panel of barcoded haploid segregants from a cross between a laboratory strain and a clinical isolate, together with both parents, was introduced intravenously into seven genetically diverse mouse strains. We measured the relative persistence of segregants in mouse brains and livers using barcode sequencing. Persistence showed transgressive segregation in both organs. On average across the two organs, yeast genotype explained 45.2% of the variance in segregant persistence, whereas yeast genotype-by-host genotype interactions explained only 2.9%. Linkage mapping showed that loci detected in more host genotypes generally explained more phenotypic variance than those detected in fewer host genotypes. At some loci, genetic variation correlated with increased yeast persistence across multiple organs (general loci) while at others increased persistence in one organ came at the cost of decreased persistence in another (antagonistic loci). General loci contributed disproportionately to brain persistence, whereas liver persistence reflected contributions from both classes. The clinical parent showed greater persistence than the laboratory parent in every host-organ combination, and the additive effects of detected loci predicted the direction of this advantage. Overall, this work shows that in this system, relative microbial persistence is polygenic, with a strong additive component and only a very small contribution from microbial genotype-by-host genotype interactions.
Related
- A non-GMO Saccharomyces cerevisiae × Saccharomyces paradoxus brewing hybrid moderately reduces ethanol production and modifies beer aroma
- Multicellularity and virulence in the budding yeast, Saccharomyces cerevisiae
- The Linker Histone Plays a Dual Role during Gametogenesis in Saccharomyces cerevisiae
- A high-throughput genetic screening protocol to measure lipid bilayer stress-induced unfolded protein response in Saccharomyces cerevisiae
- Characterisation of Saccharomyces cerevisiae and Saccharomyces jurei hybrids for oenological applications
BibTeX
@misc{ehrenreich2026largely,
title = {{A largely shared genetic architecture underlies Saccharomyces cerevisiae persistence across different mouse host genotypes}},
author = {I. M. Ehrenreich and B. Bernardo and Y. Eoh and M. D. Dean},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.04.764303},
url = {https://www.biorxiv.org/content/10.64898/2026.11.04.764303v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - A largely shared genetic architecture underlies Saccharomyces cerevisiae persistence across different mouse host genotypes
AU - I. M. Ehrenreich
AU - B. Bernardo
AU - Y. Eoh
AU - M. D. Dean
PY - 2026
DA - 2026/11/04
PB - bioRxiv
DO - 10.64898/2026.11.04.764303
UR - https://www.biorxiv.org/content/10.64898/2026.11.04.764303v1
AB - The extent to which interactions between microbial and host genotypes shape opportunistic pathogen persistence within hosts is an important open question. To assess the contribution of these interactions to persistence, we used Saccharomyces cerevisiae, a genetically tractable model for studying opportunistic fungal persistence in mammalian hosts. A pooled panel of barcoded haploid segregants from a cross between a laboratory strain and a clinical isolate, together with both parents, was introduced intravenously into seven genetically diverse mouse strains. We measured the relative persistence of segregants in mouse brains and livers using barcode sequencing. Persistence showed transgressive segregation in both organs. On average across the two organs, yeast genotype explained 45.2% of the variance in segregant persistence, whereas yeast genotype-by-host genotype interactions explained only 2.9%. Linkage mapping showed that loci detected in more host genotypes generally explained more phenotypic variance than those detected in fewer host genotypes. At some loci, genetic variation correlated with increased yeast persistence across multiple organs (general loci) while at others increased persistence in one organ came at the cost of decreased persistence in another (antagonistic loci). General loci contributed disproportionately to brain persistence, whereas liver persistence reflected contributions from both classes. The clinical parent showed greater persistence than the laboratory parent in every host-organ combination, and the additive effects of detected loci predicted the direction of this advantage. Overall, this work shows that in this system, relative microbial persistence is polygenic, with a strong additive component and only a very small contribution from microbial genotype-by-host genotype interactions.
ER -