  Phenotypes of individuals in a population of organisms are not fixed.
Phenotypic fluctuations, which describe temporal variation of the phenotype of
an individual or individual-to-individual variation across a population, are
present in populations from microbes to higher animals. Phenotypic fluctuations
can provide a basis for adaptation and be the target of selection. Here we
present a theoretical and experimental investigation of the fate of phenotypic
fluctuations in directed evolution experiments where phenotypes are subject to
constraints. We show that selecting bacterial populations for fast migration
through a porous environment drives a reduction in cell-to-cell variation
across the population. Using sequencing and genetic engineering we study the
genetic basis for this reduction in phenotypic fluctuations. We study the
generality of this reduction by developing a simple, abstracted, numerical
simulation model of the evolution of phenotypic fluctuations subject to
constraints. Using this model we find that strong and weak selection generally
lead respectively to increasing or decreasing cell-to-cell variation as a
result of a bound on the selected phenotype under a wide range of parameters.
However, other behaviors are also possible, and we describe the outcome of
selection simulations for different model parameters and suggest future
experiments. We analyze the mechanism of the observed reduction of phenotypic
fluctuations in our experimental system, discuss the relevance of our abstract
model to the experiment and explore its broader implications for evolution.
