---

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.

---

Francesca Macaluso, IFOM Milan
Seminar Room 0.02 ETP
Contact: Tobias Bollenbach