Genetic studies of the lac repressor. I. Correlation of mutational sites with specific amino acid residues: construction of a colinear gene-protein map.

By Jeffrey H. Miller, D. Ganem, P. Lu, A. Schmitz. 1977

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A formal perturbation equation between genotype and phenotype determines the Evolutionary Action of protein-coding variations on fitness (2014, methodology): “coli assayed for their impact on b-galactosidase repression (Markiewicz et al. 1994); 2015 lysozyme”
Ψ-Φ: Exploring the outer limits of bacterial pseudogenes (2004, background): “Comprehensive studies of the lac repressor gene by site-directed mutagenesis showed that about half of the missense substitutions will completely destroy protein function, and that many of these involve radical changes from the original amino acid (Gordon et al. 1988; Kleina and Miller 1990).”
Predicting deleterious amino acid substitutions. (2001, methodology): “Positions in the Escherichia coli lac repressor gene were mutated individually to amber nonsense codons (Markiewicz et al. 1994; Suckow et al. 1996).”
Large-scale discovery of induced point mutations with high-throughput TILLING. (2003, background): “Considering that about half of missense mutations are expected to be damaging to a typical protein (Markiewicz et al. 1994), we estimate that about 8 of the 16 expected missense mutations in the average 1-kb region will be useful for phenotypic analysis.”