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Complex genetics cause and constrain fungal persistence in different parts of the mammalian body.

ABSTRACT: 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 DNA 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 vs 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 nonbrain 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.

SUBMITTER: Mullis MN

PROVIDER: S-EPMC9630980 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Complex genetics cause and constrain fungal persistence in different parts of the mammalian body.

Mullis Martin N MN Ghione Caleb C Lough-Stevens Michael M Goldstein Ilan I Matsui Takeshi T Levy Sasha F SF Dean Matthew D MD Ehrenreich Ian M IM

Genetics 20221101 3

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 DNA barcodes, we tracked the relative abundances of 822 genotyped, haploid segregan ...[more]

PMID: 36103708

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Dataset Information

Complex genetics cause and constrain fungal persistence in different parts of the mammalian body.

Publications

Complex genetics cause and constrain fungal persistence in different parts of the mammalian body.

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