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.

A fitness trade-off explains the early fate of yeast aneuploids with chromosome gains / S. Pompei, M. Cosentino Lagomarsino. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 1091-6490. - 120:15(2023 Apr 05), pp. e2211687120.1-e2211687120.12. [10.1073/pnas.2211687120]

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

M. Cosentino Lagomarsino
Ultimo
2023

Abstract

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.
aneuploidy; cancer evolution; evolutionary modeling; yeast evolution;
Settore FIS/02 - Fisica Teorica, Modelli e Metodi Matematici
Settore BIO/18 - Genetica
Settore FIS/07 - Fisica Applicata(Beni Culturali, Ambientali, Biol.e Medicin)
5-apr-2023
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/1027683
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