2021
DOI: 10.15252/embj.2021108225
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Epistasis, aneuploidy, and functional mutations underlie evolution of resistance to induced microtubule depolymerization

Abstract: Cells with blocked microtubule polymerization are delayed in mitosis, but eventually manage to proliferate despite substantial chromosome missegregation. While several studies have analyzed the first cell division after microtubule depolymerization, we have asked how cells cope long-term with microtubule impairment. We allowed 24 clonal populations of yeast cells with beta-tubulin mutations preventing proper microtubule polymerization, to evolve for ~150 generations. At the end of the laboratory evolution expe… Show more

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Cited by 15 publications
(20 citation statements)
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“…This timeline of adaptation supports the theory that aneuploidy often provides a rapid but temporary form of adaptation, as has previously been observed in yeast adapted to heat stress or a tubulin mutation (Yona et al, 2012; Pavani et al, 2021). In both of those studies, a single chromosome was gained early in the adaptation process and sometimes lost again at later time points.…”
Section: Discussionsupporting
confidence: 88%
“…This timeline of adaptation supports the theory that aneuploidy often provides a rapid but temporary form of adaptation, as has previously been observed in yeast adapted to heat stress or a tubulin mutation (Yona et al, 2012; Pavani et al, 2021). In both of those studies, a single chromosome was gained early in the adaptation process and sometimes lost again at later time points.…”
Section: Discussionsupporting
confidence: 88%
“…In yeast, the development of aneuploidy resulting from an accidental chromosome missegregation has been characterized with massive experimental data [36, 610, 13, 14, 1416]. As a consequence of this major effort, we are in need of unifying principles to rationalize this wealth of data, and embed the underlying evolutionary dynamics into simple quantitative models.…”
Section: Discussionmentioning
confidence: 99%
“…The model introduced here can be extended to describe more complex scenarios. First, it can be applied to investigate the evolutionary consequences of a sudden increase of the mis-segregation rate [6], which can result from the usage of anti-mitotic drugs. Second, it can be used as an ingredient to build models of chromosomal instability, with a clear interest for cancer development [53].…”
Section: Discussionmentioning
confidence: 99%
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