Experimental Studies of Pleiotropy and Epistasis Inescherichia Coli. I. Variation in Competitive Fitness Among Mutants Resistant to Virus T4

Mutants selected for novel phenotypes frequently exhibit maladaptive pleiotropic effects. One may reasonably ask whether these effects are properties of the novel phenotypes per se, or whether these effects depend upon the particular genotypes conferring the novel phenotypes. To address this issue, I examined an array of independent mutants, derived from Escherichia coli B, that were all completely resistant to the virus T4. Each resistant mutant had maladaptive pleiotropic effects, but there was highly significant variation in competitive fitness among mutants. The degree of reduction in competitive fitness was strongly associated with cross-resistance to virus T7 and with the inferred position of the mutated gene in a complex metabolic pathway. This variation in competitive fitness permits refinement of the resistant phenotype by selection among resistant genotypes. This mechanism complements refinement of the resistant phenotype by selection for epistatic modifiers of maladaptive pleiotropic effects.