Helen Alexander

Modelling mutations in bacteria: causes and consequences of phenotypic delay

As the ultimate source of genetic variation, mutations constitute a fundamental process in evolution. Estimating the rate at which mutations occur and understanding their effects are thus key biological questions. The necessity to treat rare mutational events stochastically has also stimulated a rich mathematical literature. I will first give an introduction to the closely intertwined experimental and theoretical methods used to study mutations, dating back to Luria and Delbrück’s Nobel Prize-winning work of the 1940s. For tractability, standard models make a number of simplifying assumptions. In particular, mutations are usually treated as an instantaneous change of type, neglecting potential delays between genetic changes and their phenotypic expression. This aspect motivated a recent collaborative project in which we experimentally quantified the extent of this delay in the model bacterium E. coli, and investigated its consequences using analytical and simulation approaches. We found that several antibiotic resistance mutations exhibit a remarkable delay of 3-4 generations, which has implications both for practical estimation of mutation rates using standard assays, and for evolutionary adaptation of bacterial populations treated with antibiotics.