PT  - JOURNAL ARTICLE
AU  - Diana Fusco
AU  - Matti Gralka
AU  - Alex Anderson
AU  - Jona Kayser
AU  - Oskar Hallatschek
TI  - Excess of mutational jackpot events in growing populations due to gene surfing
AID  - 10.1101/053405
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 053405
4099  - http://biorxiv.org/content/early/2016/05/16/053405.short
4100  - http://biorxiv.org/content/early/2016/05/16/053405.full
AB  - One of the hallmarks of spontaneous mutations in growing populations is the emergence of mutational jackpot events - large mutant clones arising from mutations that by chance occur early in the development of a cellular population so that their progenitors benefit from prolonged growth. Due to their sheer size, these jackpot events, first discovered by Luria and Delbrück [1], are thought to have momentous roles in short-term evolutionary processes, including the adaptation from standing variation [2–4], evolutionary rescue [5], drug resistance evolution [6–10], and the somatic evolution of genetic diseases [11, 12]. However, because the emergence of jackpot events has been understood only in uniformly growing populations [1, 10, 13], it is currently impossible to predict their impact on the evolution of many naturally structured populations. To study jackpot events in spatially structured populations, we tracked mutant clones in microbial populations using fluorescent microscopy and population sequencing. High-frequency mutations were massively enriched in microbial colonies compared to well-shaken liquid cultures, as a result of late-occurring mutations surfing at the edge of range expansions [14–16]. We provide a mathematical theory that explains the observed excess of jackpot events and predicts their role in promoting rare evolutionary outcomes. In particular, we show that resistant clones generated by surfing can become unleashed under high selection pressures, and thus represent a drug resistance hazard for high-dose drug treatments. An excess of mutational jackpot events is shown to be a general consequence of non-uniform growth and, therefore, could be relevant to the mutational load of developing biofilm communities, solid tumors and multi-cellular organisms.