Fitness landscapes

Description In order to adapt to changing conditions, organisms evolve by the successive fixation of beneficial mutations. The effect of a beneficial mutation will often depend on the genetic background on which it occurs. When mutations affect each other’s function they display epistasis. If the genetic basis underlying adaptation is known, one can genetically engineer all possible combinations between a set of mutations to construct part of the so-called fitness landscape. We have done this for a set of mutations in the enzyme TEM-1 β-lactamase that increase resistance to the antibiotic cefotaxime. The same mutations also increase resistance to other antibiotics, and we would like to investigate whether the topology of the fitness landscape remains the same upon exposure to other antibiotics.

Used skills: Basic molecular techniques, including PCR, cloning into expression vectors, transformation to bacterial hosts, restriction and sequence analysis; MIC assays; simple bioinformatics and statistical analysis to interpret evolved enzymes.

Requirements: Molecular and Evolutionary Ecology (GEN20304) and Genetic Analyses Tools and Concepts (GEN30306) are a good preparation.

Reference: Weinreich et al. 2006 Darwinian evolution can follow only very few mutational paths to fitter proteins. Science 312: 111-114.