Fitness and functional landscapes of the E. coli RNase III gene rnc

The relationships between protein sequence, protein structure, protein function, and organismal fitness are key to understanding the molecular basis for the fitness effects of mutations. How protein properties such as protein activity and protein essentiality affect the distribution of fitness effects (DFE) of mutations are important questions in protein evolution. Deep mutational scanning studies typically measure the effects of a comprehensive set of mutations on either protein activity or fitness. Our understanding of the underpinnings of the DFE would be enhanced by a comprehensive study of both for the same gene. Here, we compared the fitness effects and in vivo protein activity effects of about 4,500 missense mutations in the rnc gene of E. coli. This gene encodes RNase III, a global regulator enzyme that cleaves diverse RNA substrates including precursor ribosomal RNA and various mRNAs including its own 5' untranslated region. Our comparative analysis revealed a strong positive correlation between fitness and functional effects, indicating that RNase III's ability to cleave dsRNA is the most important determinant of the fitness effects of rnc mutations.