Tuning Spatial Profiles of Selection Pressure to Modulate the Evolution of Drug Resistance.

ABSTRACT: Spatial heterogeneity plays an important role in the evolution of drug resistance. While recent studies have indicated that spatial gradients of selection pressure can accelerate resistance evolution, much less is known about evolution in more complex spatial profiles. Here we use a stochastic toy model of drug resistance to investigate how different spatial profiles of selection pressure impact the time to fixation of a resistant allele. Using mean first passage time calculations, we show that spatial heterogeneity accelerates resistance evolution when the rate of spatial migration is sufficiently large relative to mutation but slows fixation for small migration rates. Interestingly, there exists an intermediate regime-characterized by comparable rates of migration and mutation-in which t

SUBMITTER: De Jong MG 

PROVIDER: S-EPMC6029889 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature