Excess of mutational jackpot events in expanding populations revealed by spatial Luria-Delbruck experiments
Diana Fusco,
Matti Gralka,
Jona Kayser,
Alex Anderson,
Oskar Hallatschek
NATURE COMMUNICATIONS
7
12760
(2016)
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The genetic diversity of growing cellular populations, such as biofilms,<br> solid tumours or developing embryos, is thought to be dominated by rare,<br> exceptionally large mutant clones. Yet, the emergence of these<br> mutational jackpot events is only understood in well-mixed populations,<br> where they stem from mutations that arise during the first few cell<br> divisions. To study jackpot events in spatially structured populations,<br> we track mutant clones in microbial populations using fluorescence<br> microscopy and population sequencing. High-frequency mutations are found<br> to be massively enriched in microbial colonies compared with well-shaken<br> liquid cultures, as a result of late-occurring mutations surfing at the<br> edge of range expansions. Thus, jackpot events can be generated not only<br> when mutations arise early but also when they occur at favourable<br> locations, which exacerbates their role in adaptation and disease. In<br> particular, because spatial competition with the wild type keeps most<br> mutant clones in a quiescent state, strong selection pressures that kill<br> the wild type promote drug resistance.
Contact
Research Group Jona Kayser
Max Planck Institute for the Science of Light Staudtstr. 2 91058 Erlangen, Germany