Francesca Macaluso

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We aimed at investigating the evolutionary path towards
resistance to microtubule hyper-stabilization. We evolved
in the lab for over 190 generations yeast cells carrying
the hyper- stabilizing tub2-150 mutation in the beta-tubulin
gene. We found that tub2-150 mutants were able to
evolve and recover the initial growth defect by two
temporally distinct solutions. The first evolutionary
solution was the selection of recurrent aneuploidies
driven by the beneficial duplication of specific genes. In
the long - term evolution, aneuploidy was substituted by
fitter point mutations in TUB genes. Some representative
TUB mutations, when re-introduced in the mutant
ancestor, rescued growth of tub2-150 cells by recovering
microtubule dynamics. Our results provide new insights
on adaptive evolution following the perturbation of an
essential component such as microtubules, and
potentially lead to the development of new strategies to
counteract the emergence of resistance to drugs which
stabilize microtubules.

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IFOM Milan
Seminar Room 0.02 ETP
Contact: Tobias Bollenbach