Complex genetics cause and constrain fungal persistence in different parts of the mammalian body
Authors: Martin Mullis 1; Caleb Ghione 1; Michael Lough-Stevens 1; Ilan Goldstein 1; Takeshi Matsui 2,3,4; Sasha Levy 2,3,4; Matthew Dean 1; Ian Ehrenreich 1
Affiliations: 1) Molecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA; 2) Joint Initiative for Metrology in Biology, Stanford, CA; 3) SLAC National Accelerator Laboratory, Menlo Park, CA; 4) Department of Genetics, Stanford University, Stanford, CA
Keywords: Complex traits
Determining how genetic polymorphisms enable certain fungi to persist in mammalian hosts can improve understanding of opportunistic fungal pathogenesis, a source of substantial human morbidity and mortality. We examined the genetic basis of fungal persistence in mice using a cross between a clinical isolate and the lab reference strain of the budding yeast Saccharomyces cerevisiae. Employing chromosomally-encoded barcodes, we tracked the relative abundances of 822 genotyped, haploid segregants in multiple organs over time and performed linkage mapping of their persistence in hosts. Detected loci showed a mix of general and antagonistically pleiotropic effects across organs. General loci showed similar effects across all organs, while antagonistically pleiotropic loci showed contrasting effects in the brain and the kidneys, liver, and spleen. Persistence in an organ required both generally beneficial alleles and organ-appropriate pleiotropic alleles. This genetic architecture resulted in many segregants persisting in the brain or in non-brain organs, but few segregants persisting in all organs. These results show complex combinations of genetic polymorphisms collectively cause and constrain fungal persistence in different parts of the mammalian body.