Mutations in iclR increase evolvability by facilitating compensation that exposes cryptic beneficial mutations in experimental populations of Escherichia coli

Evolvability describes the potential of a population to generate beneficial variation. Several mechanisms that increase evolvability have been demonstrated, including the action of systems that reveal accumulated beneficial variants following an environmental shift. We examine the basis of an increase in the evolvability of Escherichia coli lines that were first selected in an environment supplemented with glucose as sole carbon source and then transferred to an otherwise identical lactose supplemented environment. These lines increased in fitness significantly more quickly in the lactose environment, and reached a higher final fitness, than did naive ancestral lines. In four of six lines this increased evolvability can be explained by mutations in iclR that were selected in glucose but were significantly deleterious in lactose, masking the effect of other generally beneficial mutations. Secondary mutations that compensated for this cost resulted in large fitness increases. We did not detect any consistent genetic signature associated with the compensation, suggesting that different pathways were responsible and, therefore, that it can occur at a relatively high rate. That mutations selected in one environment will become deleterious following an environmental shift, so that compensation provides potential for a large subsequent fitness increase represents a potentially common and general mechanism of evolvability in changing environments.