Mutational Pathway Determines Whether Drug Gradients Accelerate Evolution

Greulich, Philip, Waclaw, Bartlomiej and Allen, Rosalind J. (2012) Mutational Pathway Determines Whether Drug Gradients Accelerate Evolution. Physical Review Letters, 109, 088101-1 to 088101-5.

Record type: Article

Abstract

Drug gradients are believed to play an important role in the evolution of bacteria resistant to antibiotics
and tumors resistant to anticancer drugs. We use a statistical physics model to study the evolution of a population of malignant cells exposed to drug gradients, where drug resistance emerges via a mutational pathway involving multiple mutations. We show that a nonuniform drug distribution has the potential to accelerate the emergence of resistance when the mutational pathway involves a long sequence of mutants with increasing resistance, but if the pathway is short or crosses a fitness valley, the evolution of resistance may actually be slowed down by drug gradients. These predictions can be verified experimentally, and may help to improve strategies for combating the emergence of resistance.

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