Abstracts (first author)
Exploring the evolvability of an antibiotic resistance enzyme
For a quantitative understanding of the process of adaptation, we need to understand its ‘raw material’, that is the properties of beneficial mutations. In my talk, I will focus on two properties in particular, the frequency distribution of fitness effects of beneficial mutations and their epistatic interactions, and how these determine the pathway and outcome of evolution. In the experiments that I will present, we study the in vitro evolution of the enzyme TEM-1 beta-lactamase, a notorious determinant of antibiotic resistance in bacteria. The first two studies are systematic investigations of the short-term evolvability of the enzyme, including the number and effects of beneficial mutations and their epistatic interactions. The last two studies address the role of the structure of the fitness landscape (caused by epistasis) and population size on long-term evolvability. Surprisingly, we find that small populations sometimes reach higher resistance than large populations, showing the important role of chance events for long-term adaptation.