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  Evolutionary rescue of resistant mutants is governed by a balance between radial expansion and selection in compact populations

Aif, S., Appold, N., Kampman, L., Hallatschek, O., & Kayser, J. (2022). Evolutionary rescue of resistant mutants is governed by a balance between radial expansion and selection in compact populations. Nature Communications, 13: 7916. doi:10.1038/s41467-022-35484-y.

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Item Permalink: https://hdl.handle.net/21.11116/0000-000C-3E2C-F Version Permalink: https://hdl.handle.net/21.11116/0000-000D-7F13-0
Genre: Journal Article

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This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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Aif, Serhii1, 2, 3, 4, Author           
Appold, Nico1, 2, 3, 4, Author           
Kampman, Lucas5, Author
Hallatschek, Oskar5, Author
Kayser, Jona1, 3, 4, Author           
Affiliations:
1Kayser Research Group, Guck Division, Max Planck Institute for the Science of Light, Max Planck Society, ou_3358770              
2International Max Planck Research School, Max Planck Institute for the Science of Light, Max Planck Society, ou_2364697              
3Friedrich-Alexander-Universität Erlangen-Nürnberg, Department Physik, ou_persistent22              
4Max-Planck-Zentrum für Physik und Medizin, Max Planck Institute for the Science of Light, Max Planck Society, ou_3164414              
5external, ou_persistent22              

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 Abstract: Mutation-mediated treatment resistance is one of the primary challenges for modern antibiotic and anti-cancer therapy. Yet, many resistance mutations have a substantial fitness cost and are subject to purifying selection. How emerging resistant lineages may escape purifying selection via subsequent compensatory mutations is still unclear due to the difficulty of tracking such evolutionary rescue dynamics in space and time. Here, we introduce a system of fluorescence-coupled synthetic mutations to show that the probability of evolutionary rescue, and the resulting long-term persistence of drug resistant mutant lineages, is dramatically increased in dense microbial populations. By tracking the entire evolutionary trajectory of thousands of resistant lineages in expanding yeast colonies we uncover an underlying quasi-stable equilibrium between the opposing forces of radial expansion and natural selection, a phenomenon we term inflation-selection balance. 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.

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Language(s): eng - English
 Dates: 2022-12-062022-12-23
 Publication Status: Published online
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 Identifiers: DOI: 10.1038/s41467-022-35484-y
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Title: Nature Communications
  Abbreviation : Nature Communications
Source Genre: Journal
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Pages: - Volume / Issue: 13 Sequence Number: 7916 Start / End Page: - Identifier: ISSN: 2041-1723