The fitness landscape of genes and proteins

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The occurrence of mutations and their ability to provide an organism with a competitive advantage is central to evolution. Mutations that provide an advantage are relatively rare. The frequency and magnitude of positive, neutral and negative mutational effects is important for the dynamics and outcome of evolutionary processes; however, this distribution of mutational effects has not been comprehensively determined due to experimental limitations. This lack of knowledge has been a major hurdle for the study of how genes and proteins evolve. In this work, engineered bacteria that function analogous to an electrical circuit called a band-pass filter, together with the extensive use of the latest DNA sequencing technology, will be used to determine the distribution of mutational effects for all possible single nucleotide substitutions in a single gene that plays an important role in the evolution of antibiotic resistance. This knowledge will be exploited to address fundamental questions in evolution and practical issues in the application of evolution to biotechnology. Graduate students involved in this research will train undergraduates and high school students through their participation in this project.