Genetic basis of mycotoxin susceptibility differences between budding yeast isolates

Abstract Micophenolic acid (MPA) is an immunosuppressant mycotoxin which impairs yeast cell growth to variable degrees depending on the genetic background. Such variation could have emerged from several phenomena, including MPA gene resistance mutations and variations in copy number and localisation...

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Autores principales:	Xtopher Quispe, Sebastián M. Tapia, Carlos Villarroel, Christian Oporto, Valentina Abarca, Verónica García, Claudio Martínez, Francisco A. Cubillos
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2eb03650811b430bae6c7cdd4fbbf6ed
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spelling	oai:doaj.org-article:2eb03650811b430bae6c7cdd4fbbf6ed2021-12-02T16:07:49ZGenetic basis of mycotoxin susceptibility differences between budding yeast isolates10.1038/s41598-017-09471-z2045-2322https://doaj.org/article/2eb03650811b430bae6c7cdd4fbbf6ed2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09471-zhttps://doaj.org/toc/2045-2322Abstract Micophenolic acid (MPA) is an immunosuppressant mycotoxin which impairs yeast cell growth to variable degrees depending on the genetic background. Such variation could have emerged from several phenomena, including MPA gene resistance mutations and variations in copy number and localisation of resistance genes. To test this, we evaluated MPA susceptibility in four S. cerevisiae isolates and genetically dissected variation through the identification of Quantitative Trait Loci. Via linkage analysis we identified six QTLs, majority of which were located within subtelomeres and co-localised with IMD2, an inosine monophosphate dehydrogenase previously identified underlying MPA drug resistance in yeast cells. From chromosome end disruption and bioinformatics analysis, it was found that the subtelomere localisation of IMD2 within chromosome ends is variable depending on the strain, demonstrating the influence of IMD2 on the natural variation in yeast MPA susceptibility. Furthermore, GxE gene expression analysis of strains exhibiting opposite phenotypes indicated that ribosome biogenesis, RNA transport, and purine biosynthesis were impaired in strains most susceptible to MPA toxicity. Our results demonstrate that natural variation can be exploited to better understand the molecular mechanisms underlying mycotoxin susceptibility in eukaryote cells and demonstrate the role of subtelomeric regions in mediating interactions with the environment.Xtopher QuispeSebastián M. TapiaCarlos VillarroelChristian OportoValentina AbarcaVerónica GarcíaClaudio MartínezFrancisco A. CubillosNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xtopher Quispe Sebastián M. Tapia Carlos Villarroel Christian Oporto Valentina Abarca Verónica García Claudio Martínez Francisco A. Cubillos Genetic basis of mycotoxin susceptibility differences between budding yeast isolates
description	Abstract Micophenolic acid (MPA) is an immunosuppressant mycotoxin which impairs yeast cell growth to variable degrees depending on the genetic background. Such variation could have emerged from several phenomena, including MPA gene resistance mutations and variations in copy number and localisation of resistance genes. To test this, we evaluated MPA susceptibility in four S. cerevisiae isolates and genetically dissected variation through the identification of Quantitative Trait Loci. Via linkage analysis we identified six QTLs, majority of which were located within subtelomeres and co-localised with IMD2, an inosine monophosphate dehydrogenase previously identified underlying MPA drug resistance in yeast cells. From chromosome end disruption and bioinformatics analysis, it was found that the subtelomere localisation of IMD2 within chromosome ends is variable depending on the strain, demonstrating the influence of IMD2 on the natural variation in yeast MPA susceptibility. Furthermore, GxE gene expression analysis of strains exhibiting opposite phenotypes indicated that ribosome biogenesis, RNA transport, and purine biosynthesis were impaired in strains most susceptible to MPA toxicity. Our results demonstrate that natural variation can be exploited to better understand the molecular mechanisms underlying mycotoxin susceptibility in eukaryote cells and demonstrate the role of subtelomeric regions in mediating interactions with the environment.
format	article
author	Xtopher Quispe Sebastián M. Tapia Carlos Villarroel Christian Oporto Valentina Abarca Verónica García Claudio Martínez Francisco A. Cubillos
author_facet	Xtopher Quispe Sebastián M. Tapia Carlos Villarroel Christian Oporto Valentina Abarca Verónica García Claudio Martínez Francisco A. Cubillos
author_sort	Xtopher Quispe
title	Genetic basis of mycotoxin susceptibility differences between budding yeast isolates
title_short	Genetic basis of mycotoxin susceptibility differences between budding yeast isolates
title_full	Genetic basis of mycotoxin susceptibility differences between budding yeast isolates
title_fullStr	Genetic basis of mycotoxin susceptibility differences between budding yeast isolates
title_full_unstemmed	Genetic basis of mycotoxin susceptibility differences between budding yeast isolates
title_sort	genetic basis of mycotoxin susceptibility differences between budding yeast isolates
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/2eb03650811b430bae6c7cdd4fbbf6ed
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Genetic basis of mycotoxin susceptibility differences between budding yeast isolates

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