Excess of mutational jackpot events in expanding populations revealed by spatial Luria-Delbrück experiments.
The genetic diversity of growing cellular populations, such as biofilms, solid tumours or developing embryos, is thought to be dominated by rare, exceptionally large mutant clones. Yet, the emergence of these mutational jackpot events is only understood in well-mixed populations, where they stem from mutations that arise during the first few cell divisions. To study jackpot events in spatially structured populations, we track mutant clones in microbial populations using fluorescence microscopy and population sequencing. High-frequency mutations are found to be massively enriched in microbial colonies compared with well-shaken liquid cultures, as a result of late-occurring mutations surfing at the edge of range expansions. Thus, jackpot events can be generated not only when mutations arise early but also when they occur at favourable locations, which exacerbates their role in adaptation and disease. In particular, because spatial competition with the wild type keeps most mutant clones in a quiescent state, strong selection pressures that kill the wild type promote drug resistance.
Department of Physics, University of California, Berkeley, California 94720, USA.|Department of Integrative Biology, University of California, Berkeley, California 94720, USA.
Diana
D
Fusco
Department of Physics, University of California, Berkeley, California 94720, USA.
Matti
M
Gralka
Department of Physics, University of California, Berkeley, California 94720, USA.|Department of Integrative Biology, University of California, Berkeley, California 94720, USA.
Jona
J
Kayser
Department of Physics, University of California, Berkeley, California 94720, USA.
Alex
A
Anderson
Department of Physics, University of California, Berkeley, California 94720, USA.|Department of Integrative Biology, University of California, Berkeley, California 94720, USA.
Oskar
O
Hallatschek
D000222:Adaptation, Physiological / Q000235:genetics; D018441:Biofilms; D003198:Computer Simulation; D004252:DNA Mutational Analysis; D004926:Escherichia coli / Q000235:genetics*; D014644:Genetic Variation; D016678:Genome; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011158:Population Growth; D015398:Signal Transduction
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