Molecular signatures of aneuploidy-driven adaptive evolution

Alaattin Kaya, Marco Mariotti, Alexander Tyshkovskiy, Xuming Zhou, Michelle L. Hulke, Siming Ma, Maxim V. Gerashchenko, Amnon Koren and Vadim N. Gladyshev ()
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Alaattin Kaya: Brigham and Women’s Hospital and Harvard Medical School
Marco Mariotti: Brigham and Women’s Hospital and Harvard Medical School
Alexander Tyshkovskiy: Brigham and Women’s Hospital and Harvard Medical School
Xuming Zhou: Brigham and Women’s Hospital and Harvard Medical School
Michelle L. Hulke: Cornell University Department of Molecular Biology and Genetics
Siming Ma: Brigham and Women’s Hospital and Harvard Medical School
Maxim V. Gerashchenko: Brigham and Women’s Hospital and Harvard Medical School
Amnon Koren: Cornell University Department of Molecular Biology and Genetics
Vadim N. Gladyshev: Brigham and Women’s Hospital and Harvard Medical School

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract Alteration of normal ploidy (aneuploidy) can have a number of opposing effects, such as unbalancing protein abundances and inhibiting cell growth but also accelerating genetic diversification and rapid adaptation. The interplay of these detrimental and beneficial effects remains puzzling. Here, to understand how cells develop tolerance to aneuploidy, we subject disomic (i.e. with an extra chromosome copy) strains of yeast to long-term experimental evolution under strong selection, by forcing disomy maintenance and daily population dilution. We characterize mutations, karyotype alterations and gene expression changes, and dissect the associated molecular strategies. Cells with different extra chromosomes accumulated mutations at distinct rates and displayed diverse adaptive events. They tended to evolve towards normal ploidy through chromosomal DNA loss and gene expression changes. We identify genes with recurrent mutations and altered expression in multiple lines, revealing a variant that improves growth under genotoxic stresses. These findings support rapid evolvability of disomic strains that can be used to characterize fitness effects of mutations under different stress conditions.

Date: 2020
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DOI: 10.1038/s41467-019-13669-2

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