Application of simultaneous selective pressures slows adaptation.

Autor: Merlo LMF; Lankenau Institute for Medical Research Wynnewood Pennsylvania USA., Sprouffske K; Disease Area Oncology Novartis Institutes for BioMedical Research Basel Switzerland., Howard TC; Department of Pathology and Laboratory Medicine UC Davis Health Sacramento California USA., Gardiner KL; School of Veterinary Medicine University of Pennsylvania Philadelphia Pennsylvania USA., Caulin AF; PEEL Therapeutics, Inc. Salt Lake City Utah USA., Blum SM; Department of Medical Oncology Dana-Farber Cancer Institute Broad Institute at MIT and Harvard Harvard Medical School, and Massachusetts General Hospital Cancer Center Boston Massachusetts USA., Evans P; Department of Biomedical and Health Informatics Children's Hospital of Philadelphia Philadelphia Pennsylvania USA., Bedalov A; Clinical Research Division Fred Hutchinson Cancer Research Center Seattle Washington USA., Sniegowski PD; Department of Biology University of Pennsylvania Philadelphia Pennsylvania USA., Maley CC; Arizona State University School of Life Sciences Biodesign Institute Tempe Arizona USA.
Jazyk: angličtina
Zdroj: Evolutionary applications [Evol Appl] 2020 Aug 15; Vol. 13 (7), pp. 1615-1625. Date of Electronic Publication: 2020 Aug 15 (Print Publication: 2020).
DOI: 10.1111/eva.13062
Abstrakt: 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 high-throughput 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.
(© 2020 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz: