Many cellular populations are tightly packed, such as microbial colonies and biofilms, or tissues and tumours in multicellular organisms. The movement of one cell in these crowded assemblages requires motion of others, so that cell displacements are correlated over many cell diameters. Whenever movement is important for survival or growth, these correlated rearrangements could couple the evolutionary fate of different lineages. However, little is known about the interplay between mechanical forces and evolution in dense cellular populations. Here, by tracking slower-growing clones at the expanding edge of yeast colonies, we show that the collective motion of cells prevents costly mutations from being weeded out rapidly. Joint pushing by neighbouring cells generates correlated movements that suppress the differential displacements required for selection to act. This mechanical screening of fitness differences allows slower-growing mutants to leave more descendants than expected under non-mechanical models, thereby increasing their chance for evolutionary rescue. Our work suggests that, in crowded populations, cells cooperate with surrounding neighbours through inevitable mechanical interactions. This effect has to be considered when predicting evolutionary outcomes, such as the emergence of drug resistance or cancer evolution.
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Imaging data used in this study are available at https://figshare.com/projects/Kayser2018_NatEE/55727.
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Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under award R01GM115851, a National Science Foundation CAREER Award (#1555330), a Simons Investigator award from the Simons Foundation (#327934), the National Energy Research Scientific Computing Center, a US Department of Energy Office of Science User Facility operated under contract number DE-AC02-05CH11231, and the Berkeley Research Computing programme at the University of California, Berkeley. J.K. acknowledges a research scholarship (KA 4486/1-1) awarded by the German Research Foundation. The authors thank B. Good, J. Paulose, M.-C. Duvernoy and S. Martis for vital discussions, and the group of J. Rine for invaluable insights on yeast genetics.
The authors declare no competing interests.
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Supplementary Text, Video Legends and Fig. 1–21.
Time lapse series of a shrinking wide-mutant sector in a linear front.
Simulation of a shrinking mutant clone.
Single cell tracking at a moderately curved front.
Single cell tracking at a highly curved front.
Single cell tracking of front cells starting at birth.
Simulation of expanding, budding yeast cell population.
Fate of a slower growing clone after expulsion from the front.
Resurgent growth of a persisting mutant sector after drug application.
Single cell tracking at the mutant–wild-type boundary.
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Kayser, J., Schreck, C.F., Gralka, M. et al. Collective motion conceals fitness differences in crowded cellular populations. Nat Ecol Evol 3, 125–134 (2019). https://doi.org/10.1038/s41559-018-0734-9
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