Pervasive compensatory adaptation in Escherichia coli

To investigate compensatory adaptation (CA), we used genotypes of Escherichia coli which were identical except for one or two deleterious mutations. We compared CA for (i) deleterious mutations with large versus small e¡ects, (ii) genotypes carrying one versus two mutations, and (iii) pairs of deleterious mutations which interact in a multiplicative versus synergistic fashion. In all, we studied 14 di¡erent genotypes, plus a control strain which was not mutated. Most genotypes showed CA during 200 genera-tions of experimental evolution, where we de¢ne CA as a ¢tness increase which is disproportionately large relative to that in evolving control lines, coupled with retention of the original deleterious mutation(s). We observed greater CA for mutations of large e¡ect than for those of small e¡ect, which can be explained by the greater bene¢t to recovery in severely handicapped genotypes given the dynamics of selection. The rates of CA were similar for double and single mutants whose initial ¢tnesses were approximately equal. CAwas faster for synergistic than for multiplicative pairs, presumably because the marginal gain which results from CA for one of the component mutations is greater in that case. The most surprising result in our view, is that compensation should be so readily achieved in an organism which is haploid and has little genetic redundancy. This ¢nding suggests a degree of versatility in the E. coli genome which demands further study from both genetic and physiological perspectives