The role of genetic redundancy in adaptive evolution of efflux pumps
In genetic redundancy, multiple genes in a genome perform the same or similar function. Although redundancy is widespread across the tree of life, its evolutionary origins are not entirely understood.  Genetic redundancy may provide a fitness benefit during evolution by increasing gene dosage and protecting critical genes from deleterious mutations. These fitness effects have been confirmed experimentally, but their long-term consequences for evolution have not been tested. In this study, I will manipulate the genomic content of efflux pump genes in E. coli and test the effect of their redundancy using directed evolution of proteins. By evolving the multidrug efflux pump AcrAB at different levels of redundancy, I will determine how the presence of other genes with overlapping drug-efflux activities affects adaptive evolution. I will compare evolutionary trajectories using comprehensive sequence and fitness analysis of the evolved efflux pump variants. This approach will provide a unique opportunity to directly test the role of genetic redundancy in evolution and help to understand why genetic redundancy is maintained in a genome.