Mutation frequencies in a birth–death branching process

Abstract

First, we revisit the stochastic Luria–Delbrück model: a classic two-type branching process which describes cell proliferation and mutation. We prove limit theorems and exact results for the mutation times, clone sizes and number of mutants. Second, we extend the framework to consider mutations at multiple sites along the genome. The number of mutants in the two-type model characterises the mean site frequency spectrum in the multiple-site model. Our predictions are consistent with previously published cancer genomic data.