Deep sequencing reveals excess of mutational jackpot events in microbial colonies. Escherichia coli

Anomalously large mutant clones are thought to shape the genetic diversity of growing cellular populations, including microbial colonies, tumors, and developing multi-cellular organisms. 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 fluorescent microscopy and population sequencing. High-frequency mutations are found to be heavily enriched in microbial colonies compared to well-shaken liquid cultures, as a result of late-occurring mutations surfing at the edge of range expansions. An excess of mutational jackpot events is shown to be a general consequence of non-uniform growth and, therefore, could be relevant to the emergence and spread of drug resistance in biofilms and solid tumors.