SKM 2023 – wissenschaftliches Programm
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BP: Fachverband Biologische Physik
BP 10: Evolution and Origin of Life
BP 10.5: Vortrag
Dienstag, 28. März 2023, 11:00–11:15, BAR 0106
Evolutionary rescue of resistant mutants is governed by a balance between radial expansion and selection in compact populations — Serhii Aif1,2, Nico Appold1,2, Lucas Kampmann3, Oskar Hallatschek3,4, and •Jona Kayser1,2 — 1MPI für die Physik des Lichts, Erlangen, Germany — 2MPZ für Physik und Medizin, Erlangen, Germany — 3University of California, Berkeley, USA — 4Leipzig University, Leipzig, Germany
Mutation-mediated treatment resistance is one of the primary challenges for modern antibiotic and anti-cancer therapy. Yet, how slower-growing resistant lineages may escape purifying selection via continued evolution is still unclear. Here, we introduce a system of fluorescence-coupled synthetic mutations to track the entire evolutionary trajectory of thousands of resistant lineages in expanding yeast colonies. We uncover that an underlying quasi-stable equilibrium between the opposing forces of radial expansion and natural selection, a phenomenon we term inflation-selection balance, enhances the evolutionary rescue of resistant lineages. Tailored computational models and agent-based simulations corroborate the fundamental nature of the observed effects and demonstrate the potential impact on drug resistance evolution in cancer. The described phenomena should be considered when predicting multi-step evolutionary dynamics in any mechanically compact cellular population, including pathogenic microbial biofilms and solid tumors. The insights gained will be especially valuable for the quantitative understanding of response to treatment, including emerging evolution-based therapy strategies.