Sequential mutations in exponentially growing populations

Abstract

Author summary In settings such as bacterial infections and cancer, cellular populations grow exponentially. DNA mutations acquired during this growth can have profound effects, e.g. conferring drug resistance or faster tumour growth. In mathematical models of this fundamental process, considerable effort—spanning many decades—has been invested to understand the factors that control two key aspects of this process: how many cells exist with a set of mutations, and how long does it take for these cells to appear. In this paper, we consider these two aspects in a general mathematical framework. Surprisingly, for both quantities, we find universal probability distributions which are valid regardless of how many mutations we focus on, and what effect these mutations might have on the cells. The distributions are elegant and easy to work with, providing a computationally efficient alternative to intensive simulation-based approaches. We demonstrate the usefulness of our mathematical results by illustrating their consequences for bacterial experiments and cancer evolution.

Publication
PLOS Computational Biology