Aneuploidy: Cells Losing Their Balance

Torres, Eduardo M.; Williams, Bret R.; Amon, Angelika

doi:10.1534/genetics.108.090878

Cited by 357 publications

(392 citation statements)

References 72 publications

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“…Indeed, whole genome and chromosomal duplication constitute crude solutions with significant overheads on the cell that are in part associated with increased copies of DNA, RNA, and proteins (1,2). Duplication of particular chromosomes (i.e., aneuploidy) creates, in addition, a stoichiometric imbalance between gene products (14,15) and promotes further genome destabilizing events (16,17). Thus, it appears that aneuploidy is concurrently advantageous and highly costly (18,19).…”

mentioning

confidence: 99%

Chromosomal duplication is a transient evolutionary solution to stress

Yona

Manor

Herbst

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

336

382

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Aneuploidy, an abnormal number of chromosomes, is a widespread phenomenon found in unicellulars such as yeast, as well as in plants and in mammalians, especially in cancer. Aneuploidy is a genomescale aberration that imposes a severe burden on the cell, yet under stressful conditions specific aneuploidies confer a selective advantage. This dual nature of aneuploidy raises the question of whether it can serve as a stable and sustainable evolutionary adaptation. To clarify this, we conducted a set of laboratory evolution experiments in yeast and followed the long-term dynamics of aneuploidy under diverse conditions. Here we show that chromosomal duplications are first acquired as a crude solution to stress, yet only as transient solutions that are eliminated and replaced by more efficient solutions obtained at the individual gene level. These transient dynamics of aneuploidy were repeatedly observed in our laboratory evolution experiments; chromosomal duplications gained under stress were eliminated not only when the stress was relieved, but even if it persisted. Furthermore, when stress was applied gradually rather than abruptly, alternative solutions appear to have emerged, but not aneuploidy. Our findings indicate that chromosomal duplication is a first evolutionary line of defense, that retains survivability under strong and abrupt selective pressures, yet it merely serves as a "quick fix," whereas more refined and sustainable solutions take over. Thus, in the perspective of genome evolution trajectory, aneuploidy is a useful yet short-lived intermediate that facilitates further adaptation.evolutionary dynamics | environmental stress | heat tolerance | pH tolerance

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mentioning

confidence: 99%

Chromosomal duplication is a transient evolutionary solution to stress

Yona

Manor

Herbst

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

336

382

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“…[7,8,18,42] This growth defect is caused by the deregulation of the proteasome, [1,[43][44][45][46] cell metabolism, [47] transcriptome, [41] and the increase in cellular senescence. [42,48] However, not all aneuploidies have the same effect on cells.…”

Section: Aneuploidy Canmentioning

confidence: 99%

CIN and Aneuploidy: Different Concepts, Different Consequences

Schukken

Foijer

2017

BioEssays

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Chromosomal instability (CIN) and aneuploidy are similar concepts but not synonymous. CIN is the process that leads to chromosome copy number alterations, and aneuploidy is the result. While CIN and resulting aneuploidy often cause growth defects, they are also selected for in cancer cells. Although such contradicting fates may seem paradoxical at first, they can be better understood when CIN and aneuploidy are assessed separately, taking into account the in vitro or in vivo context, the rate of CIN, and severity of the aneuploid karyotype. As CIN can only be measured in living cells, which proves to be technically challenging in vivo, aneuploidy is more frequently quantified. However, CIN rates might be more predictive for tumor outcome than assessing aneuploidy rates alone. In reviewing the literature, we therefore conclude that there is an urgent need for new models in which we can monitor chromosome mis-segregation and its consequences in vivo. Also see the video abstract here: https://youtu.be/fL3LxZduchg

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“…[1][2][3][4] Thus, cell cycle analysis not only constitutes a specific field of research on its own but also contributes important information to many areas within biological and medical sciences. Generally, monitoring DNA contents of a large number of cells is best performed using flow cytometry.…”

Section: Introductionmentioning

confidence: 99%

“…Accordingly, measurement of fluorescence intensity per cell allows discrimination of cells from the various phases of the cell cycle (G 0 /G 1 , S, G 2 /M) and quantification of the percentages of polyploid cells as well as apoptotic/necrotic cell fragments with DNA contents smaller than 2N (subG 1 -fragments). Additionally, aberrant DNA contents (aneuploidy), a characteristic of many cancer cells, 4 can be identified. Indicative of high-quality cell cycle analysis is the lack of preparation-derived DNA-containing cell debris and a good Cell cycle alterations are fundamental to many physiological processes but their detection has proven difficult when cells are in the context of a tissue structure.…”

Section: Introductionmentioning

confidence: 99%