2022
DOI: 10.1101/2022.07.07.499182
|View full text |Cite
Preprint
|
Sign up to set email alerts
|

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

Abstract: The early development of aneuploidy from an accidental chromosome missegregation shows contrasting effects. On the one hand, it is associated to 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 modelin… Show more

Help me understand this report
View published versions

Search citation statements

Order By: Relevance

Paper Sections

Select...
4
1

Citation Types

1
12
0

Year Published

2023
2023
2024
2024

Publication Types

Select...
4
1

Relationship

2
3

Authors

Journals

citations
Cited by 5 publications
(13 citation statements)
references
References 86 publications
1
12
0
Order By: Relevance
“…In other words, the combination of two mechanisms that independently cause azole tolerance can dramatically increase the growth of fungal cells in drug, resulting in bona fide azole resistance. Multiple simultaneous mutations are common in cancer cells and often lead to treatment failure [7679]. Our results highlight the diverse trajectories that C. albicans can take during adaptation to antifungal drugs and support that two independent mechanisms of tolerance (point mutation and aneuploidy) can evolve within the same cell resulting in drug resistance.…”
Section: Discussionsupporting
confidence: 62%
“…In other words, the combination of two mechanisms that independently cause azole tolerance can dramatically increase the growth of fungal cells in drug, resulting in bona fide azole resistance. Multiple simultaneous mutations are common in cancer cells and often lead to treatment failure [7679]. Our results highlight the diverse trajectories that C. albicans can take during adaptation to antifungal drugs and support that two independent mechanisms of tolerance (point mutation and aneuploidy) can evolve within the same cell resulting in drug resistance.…”
Section: Discussionsupporting
confidence: 62%
“…CINner models cancer evolution as a branching process [11]. Cell lifespan is exponentially distributed with an input turn-over rate, similar to previous works [12,13]. At the end of its lifespan, the cell either divides or dies.…”
Section: Resultsmentioning
confidence: 99%
“…However, the CNAs in this approach do not affect the phylogeny tree, therefore karyotype selection is not explicitly depicted. Some recent studies model the effects of selection and missegregation on subclonal copy numbers [18,68], also incorporating point mutations [13] or WGD [46,69]. Nevertheless, many of these models focus only on the average ploidy and do not consider chromosome-specific CN [13,46,68].…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Our model provides a quantitative framework to describe both perturbations jointly. We speculate that this quantitative understanding could be useful to predict the fitness landscape of situations with perturbed gene dosage, such as large-scale gene duplications in absence of dosage-compensation mechanisms (Pompei and Lagomarsino, 2023). In addition, our model provides a method to rigorously test the presence of transcriptional limitations by considering how the cost of overexpression varies as the mRNA stability of the unnecessary protein changes.…”
Section: Discussionmentioning
confidence: 99%