Effect of aneuploidy on cellular adaptation to hyper-osmotic and ionic stress

Aneuploidy, the condition of having an impaired karyotype is a distinctive characteristic of cancer cells and has been proposed to promote cancer evolution by conferring drug resistance and aggressive phenotypes. At a cellular level, aneuploidy, by massively changing the transcriptome and the proteo...

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Main Author: Natali, Federica
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Format: Thesis-Doctor of Philosophy
Language:English
Published: Nanyang Technological University 2022
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Online Access:https://hdl.handle.net/10356/161063
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spelling sg-ntu-dr.10356-1610632023-02-28T18:34:58Z Effect of aneuploidy on cellular adaptation to hyper-osmotic and ionic stress Natali, Federica - School of Biological Sciences Singapore Institute of Food and Biotechnology Innovation (SIFBI) Singapore Institute of Food and Biotechnology Innovation (SIFBI) Prakash Arumugam PARUMUGAM@sifbi.astar.edu.sg Science::Biological sciences::Evolution Science::Biological sciences::Microbiology::Microorganisms Science::Biological sciences::Molecular biology Aneuploidy, the condition of having an impaired karyotype is a distinctive characteristic of cancer cells and has been proposed to promote cancer evolution by conferring drug resistance and aggressive phenotypes. At a cellular level, aneuploidy, by massively changing the transcriptome and the proteome, has a profound impact on cellular phenotype. Specifically, aneuploidy has negative effect on cellular fitness in normal growth conditions in which euploid cells are already optimized to live. However, when the growth conditions are unfavorable, different aneuploid strains showed improved growth in different environmental or genetic perturbations. Adaptive mechanisms were linked to upregulation of specific genes on the aneuploid chromosome, suggesting that cells with different karyotypes have different phenotypes and fitness potential. At the same time, aneuploidy has been shown to promote further chromosome and genetic instability that could lead to the generation of a genomically heterogeneous aneuploid populations. I therefore hypothesize that aneuploidy might increase cellular evolvability via two mechanisms: first aneuploidy increases genetic and karyotypic instability and therefore generates population of cells carrying different phenotypes. Second, each different karyotype is associated with a different set of phenotypes. Therefore, these two mechanisms combined increase phenotypic variation which ultimately leads to higher adaptive potential. The aim of my project, performed using the yeast S. cerevisiae, is to test if evolvability of euploid and aneuploid cellular populations correlates with their level of genomic instability, when cells are challenged with an environmental perturbation. For this purpose, a collection of isogenic euploid and aneuploid yeast strains containing simple and complex karyotypes has been evolved in different conditions through serial passages, and evolution has been assessed as deviation from initial ratio in competition experiments between strains of same ploidy tagged with two fluorophores. Doctor of Philosophy 2022-08-15T03:10:31Z 2022-08-15T03:10:31Z 2022 Thesis-Doctor of Philosophy Natali, F. (2022). Effect of aneuploidy on cellular adaptation to hyper-osmotic and ionic stress. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/161063 https://hdl.handle.net/10356/161063 10.32657/10356/161063 en This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). application/pdf Nanyang Technological University
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Biological sciences::Evolution
Science::Biological sciences::Microbiology::Microorganisms
Science::Biological sciences::Molecular biology
spellingShingle Science::Biological sciences::Evolution
Science::Biological sciences::Microbiology::Microorganisms
Science::Biological sciences::Molecular biology
Natali, Federica
Effect of aneuploidy on cellular adaptation to hyper-osmotic and ionic stress
description Aneuploidy, the condition of having an impaired karyotype is a distinctive characteristic of cancer cells and has been proposed to promote cancer evolution by conferring drug resistance and aggressive phenotypes. At a cellular level, aneuploidy, by massively changing the transcriptome and the proteome, has a profound impact on cellular phenotype. Specifically, aneuploidy has negative effect on cellular fitness in normal growth conditions in which euploid cells are already optimized to live. However, when the growth conditions are unfavorable, different aneuploid strains showed improved growth in different environmental or genetic perturbations. Adaptive mechanisms were linked to upregulation of specific genes on the aneuploid chromosome, suggesting that cells with different karyotypes have different phenotypes and fitness potential. At the same time, aneuploidy has been shown to promote further chromosome and genetic instability that could lead to the generation of a genomically heterogeneous aneuploid populations. I therefore hypothesize that aneuploidy might increase cellular evolvability via two mechanisms: first aneuploidy increases genetic and karyotypic instability and therefore generates population of cells carrying different phenotypes. Second, each different karyotype is associated with a different set of phenotypes. Therefore, these two mechanisms combined increase phenotypic variation which ultimately leads to higher adaptive potential. The aim of my project, performed using the yeast S. cerevisiae, is to test if evolvability of euploid and aneuploid cellular populations correlates with their level of genomic instability, when cells are challenged with an environmental perturbation. For this purpose, a collection of isogenic euploid and aneuploid yeast strains containing simple and complex karyotypes has been evolved in different conditions through serial passages, and evolution has been assessed as deviation from initial ratio in competition experiments between strains of same ploidy tagged with two fluorophores.
author2 -
author_facet -
Natali, Federica
format Thesis-Doctor of Philosophy
author Natali, Federica
author_sort Natali, Federica
title Effect of aneuploidy on cellular adaptation to hyper-osmotic and ionic stress
title_short Effect of aneuploidy on cellular adaptation to hyper-osmotic and ionic stress
title_full Effect of aneuploidy on cellular adaptation to hyper-osmotic and ionic stress
title_fullStr Effect of aneuploidy on cellular adaptation to hyper-osmotic and ionic stress
title_full_unstemmed Effect of aneuploidy on cellular adaptation to hyper-osmotic and ionic stress
title_sort effect of aneuploidy on cellular adaptation to hyper-osmotic and ionic stress
publisher Nanyang Technological University
publishDate 2022
url https://hdl.handle.net/10356/161063
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