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A fitness trade-off explains the early fate of yeast aneuploids with chromosome gains

The early development of aneuploidy from an accidental chromosome missegregation shows contrasting effects. On the one hand, it is associated with significant cellular stress and decreased fitness. On the other hand, it often carries a beneficial effect and provides a quick (but typically transient)...

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Autores principales: Pompei, Simone, Cosentino Lagomarsino, Marco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10104565/
https://www.ncbi.nlm.nih.gov/pubmed/37018197
http://dx.doi.org/10.1073/pnas.2211687120
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author Pompei, Simone
Cosentino Lagomarsino, Marco
author_facet Pompei, Simone
Cosentino Lagomarsino, Marco
author_sort Pompei, Simone
collection PubMed
description The early development of aneuploidy from an accidental chromosome missegregation shows contrasting effects. On the one hand, it is associated with significant cellular stress and decreased fitness. On the other hand, it often carries a beneficial effect and provides a quick (but typically transient) solution to external stress. These apparently controversial trends emerge in several experimental contexts, particularly in the presence of duplicated chromosomes. However, we lack a mathematical evolutionary modeling framework that comprehensively captures these trends from the mutational dynamics and the trade-offs involved in the early stages of aneuploidy. Here, focusing on chromosome gains, we address this point by introducing a fitness model where a fitness cost of chromosome duplications is contrasted by a fitness advantage from the dosage of specific genes. The model successfully captures the experimentally measured probability of emergence of extra chromosomes in a laboratory evolution setup. Additionally, using phenotypic data collected in rich media, we explored the fitness landscape, finding evidence supporting the existence of a per-gene cost of extra chromosomes. Finally, we show that the substitution dynamics of our model, evaluated in the empirical fitness landscape, explains the relative abundance of duplicated chromosomes observed in yeast population genomics data. These findings lay a firm framework for the understanding of the establishment of newly duplicated chromosomes, providing testable quantitative predictions for future observations.
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spelling pubmed-101045652023-10-05 A fitness trade-off explains the early fate of yeast aneuploids with chromosome gains Pompei, Simone Cosentino Lagomarsino, Marco Proc Natl Acad Sci U S A Physical Sciences The early development of aneuploidy from an accidental chromosome missegregation shows contrasting effects. On the one hand, it is associated with significant cellular stress and decreased fitness. On the other hand, it often carries a beneficial effect and provides a quick (but typically transient) solution to external stress. These apparently controversial trends emerge in several experimental contexts, particularly in the presence of duplicated chromosomes. However, we lack a mathematical evolutionary modeling framework that comprehensively captures these trends from the mutational dynamics and the trade-offs involved in the early stages of aneuploidy. Here, focusing on chromosome gains, we address this point by introducing a fitness model where a fitness cost of chromosome duplications is contrasted by a fitness advantage from the dosage of specific genes. The model successfully captures the experimentally measured probability of emergence of extra chromosomes in a laboratory evolution setup. Additionally, using phenotypic data collected in rich media, we explored the fitness landscape, finding evidence supporting the existence of a per-gene cost of extra chromosomes. Finally, we show that the substitution dynamics of our model, evaluated in the empirical fitness landscape, explains the relative abundance of duplicated chromosomes observed in yeast population genomics data. These findings lay a firm framework for the understanding of the establishment of newly duplicated chromosomes, providing testable quantitative predictions for future observations. National Academy of Sciences 2023-04-05 2023-04-11 /pmc/articles/PMC10104565/ /pubmed/37018197 http://dx.doi.org/10.1073/pnas.2211687120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Physical Sciences
Pompei, Simone
Cosentino Lagomarsino, Marco
A fitness trade-off explains the early fate of yeast aneuploids with chromosome gains
title A fitness trade-off explains the early fate of yeast aneuploids with chromosome gains
title_full A fitness trade-off explains the early fate of yeast aneuploids with chromosome gains
title_fullStr A fitness trade-off explains the early fate of yeast aneuploids with chromosome gains
title_full_unstemmed A fitness trade-off explains the early fate of yeast aneuploids with chromosome gains
title_short A fitness trade-off explains the early fate of yeast aneuploids with chromosome gains
title_sort fitness trade-off explains the early fate of yeast aneuploids with chromosome gains
topic Physical Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10104565/
https://www.ncbi.nlm.nih.gov/pubmed/37018197
http://dx.doi.org/10.1073/pnas.2211687120
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