POPULATION GENETICS OF NEUTRAL MUTATIONS IN EXPONENTIALLY GROWING CANCER CELL POPULATIONS

Abstract

In order to analyze data from cancer genome sequencing projects, we need to be able to distinguish causative, or "driver," mutations from "passenger" mutations that have no selective effect. Toward this end, we prove results concerning the frequency of neutural mutations in exponentially growing multitype branching processes that have been widely used in cancer modeling. Our results yield a simple new population genetics result for the site frequency spectrum of a sample from an exponentially growing population.

Keywords: Exponentially growing population; cancer model; multitype branching process; site frequency spectrum.

FIG. 1

Simulated site frequency spectrum when ν = γ, sample size n = 10, and population size N = 100,000.

FIG. 2

Genealogy of wave 2 individuals. Here 0.6, 0.25, and 0.1 are the fractions of the type 1 population derived from the three most prolific type 1 mutations. If these numbers look odd recall that in the example ER = 1/2 for wave 1, while (0.6)² + (0.25)² + (0.1)² = 0.4325.