Application of simultaneous selective pressures slows adaptation
Abstract
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. 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. 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 highâthroughput sequencing. 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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 01, 2020
- Source ID
- 10.1111/eva.13062
Entities
People
- Aleah F. Caulin
- Antonio Bedalov
- Carlo Maley
- Kathleen Sprouffske
- Kristin L. Gardiner
- Lauren M. F. Merlo
- Paul D. Sniegowski
- Perry Evans
- Steven M. Blum
- Taylor C. Howard
Organizations
- American Association for Cancer Research
- Arizona State University
- Children's Hospital of Philadelphia
- Congressionally Directed Medical Research Programs
- Fred Hutchinson Cancer Center
- Lankenau Institute for Medical Research
- National Institutes of Health Clinical Center
- Savannah River Operations Office
- University of California, Davis
- University of Pennsylvania