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Abstract:
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.
