Beneficial mutations can become costly following an environmental
change. Compensatory mutations can relieve these costs, while not
affecting the selected function, so that the benefits are retained if
the environment shifts back to be similar to the one in which the
beneficial mutation was originally selected. Compensatory mutations have
been extensively studied in the context of antibiotic resistance,
responses to specific genetic perturbations and in the determination of
interacting gene network components. Few studies have focused on the
role of compensatory mutations during more general adaptation,
especially as the result of selection in fluctuating environments where
adaptations to different environment components may often involve
tradeoffs. We examine if costs of a mutation in lacI, which deregulated
expression of the lac operon in evolving populations of Escherichia coli
bacteria, was compensated. This mutation occurred in multiple replicate
populations selected in environments that fluctuated between growth on
lactose, where the mutation was beneficial, and on glucose, where it was
deleterious. We found that compensation for the cost of the lacI
mutation was rare, but, when it did occur, it did not negatively affect
the selected benefit. Compensation was not more likely to occur in a
particular evolution environment. Compensation has the potential to
remove pleiotropic costs of adaptation, but its rarity indicates that
the circumstances to bring about the phenomenon may be peculiar to each
individual or impeded by other selected mutations.