The role of migration in mutant evolution in fragmented populations

Abstract

AbstractMutant evolution in fragmented populations has been studied extensively in evolutionary biology. With an increased focus on evolutionary dynamics in medical research, quantification of mutant load in fragmented populations with varying levels of migration has become especially important. Examples of fragmented populations are hematopoietic stem cell niches in the bone marrow where cells can re-circulate between niches through the blood, or colonic crypts where movement of cells across different crypts is not thought to be common. Here we use a combination of experiments and theory to investigate the role of migration in mutant distribution. In the case of neutral mutants, the experiments confirmed that while the mean number of mutants is not influenced by migration, the probability distribution is, which manifested itself in a change in the skewedness of the distribution of the mutant numbers in the demes. In the case of disadvantageous mutants, we investigated the phenomenon of the increase in the expected number of mutants compared to that of the selection-mutation balance. In a single deme, this increase is observed when the deme size is lower than the critical size, Nc. In a fragmented system that consists of connected demes with a probability of migration, the increase in mutant numbers above the selection-mutation balance can be maintained in small (N < Nc) demes as long as the migration rate is sufficiently small. The migration rate above which the mutants approach the selection-mutation balance decays exponentially with N/Nc. These findings are relevant in the context of the complex and poorly understood processes that may lead to changes in the clonal composition in tissues and tumors.