Mutations in Expanding Populations

In spatially constrained growing populations, such as tumors or biofilms, cells at the edge of expanding front have significant advantages because of the high accessibility to nutrients and spaces. Therefore, mutations that happen at the front have a large probability to surf at the edge of the population. A previous population sequencing study has shown that this effect leaves characteristic features in the mutation frequency spectrum. However, sequencing experiments cannot capture the behavior of low-frequency variants. Here, we constructed a microfluidic device to track mutations which happened at the front of a population growth. Combining with agent-based simulations and theoretical studies, we found that low-frequency mutant clones have broadly distributed shapes and sizes, which result from the combination of growth and excluded volume interactions. These results could be relevant to the emergence of drug resistance in crowded cellular populations.