Application of simultaneous selective pressures slows adaptation

Background and objectives: Beneficial mutations that arise in an evolving
asexual population may compete or interact in ways that alter the overall
rate of adaptation through mechanisms such as clonal or functional
interference. The application of multiple selective pressures
simultaneously may allow for a greater number of adaptive mutations,
increasing the opportunities for competition between selectively
advantageous alterations, and thereby reducing the rate of adaptation.
Methodology: We evolved a strain of Saccharomyces cerevisiae that could
not produce its own histidine or uracil for ~500 generations under one or
three selective pressures: limitation of the concentration of glucose,
histidine, and/or uracil in the media. The rate of adaptation was obtained
by measuring evolved relative fitness using competition assays. Results:
Populations evolved under a single selective pressure showed a
statistically significant increase in fitness on those pressures relative
to the ancestral strain, but the populations evolved on all three
pressures did not show a statistically significant increase in fitness
over the ancestral strain on any single pressure. Simultaneously limiting
three essential nutrients for a population of S. cerevisiae effectively
slows the rate of evolution on any one of the three selective pressures
applied, relative to the single selective pressure cases. We identify
possible mechanisms for fitness changes seen between populations evolved
on one or three limiting nutrient pressures by high-throughput sequencing.
Conclusions and implications: Adding multiple selective pressures to
evolving disease like cancer and infectious diseases could reduce the rate
of adaptation and thereby may slow disease progression, prolong drug
efficacy and prevent deaths.