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Natural variation in the consequences of gene overexpression and its implications for evolutionary trajectories

Journal Article · · eLife
DOI:https://doi.org/10.7554/eLife.70564· OSTI ID:1811587
 [1];  [2];  [3];  [3];  [4]
  1. Microbiology Doctoral Training Program, University of Wisconsin-Madison, Madison, United States
  2. Great Lakes Bioenergy Research Center, University of Wisconsin-Madison, Madison, United States
  3. Center for Genomic Science Innovation, University of Wisconsin-Madison, Madison, United States
  4. Great Lakes Bioenergy Research Center, University of Wisconsin-Madison, Madison, United States, Center for Genomic Science Innovation, University of Wisconsin-Madison, Madison, United States, Department of Medical Genetics, University of Wisconsin-Madison, Madison, United States

Copy number variation through gene or chromosome amplification provides a route for rapid phenotypic variation and supports the long-term evolution of gene functions. Although the evolutionary importance of copy-number variation is known, little is understood about how genetic background influences its tolerance. Here, we measured fitness costs of over 4000 overexpressed genes in 15 Saccharomyces cerevisiae strains representing different lineages, to explore natural variation in tolerating gene overexpression (OE). Strain-specific effects dominated the fitness costs of gene OE. We report global differences in the consequences of gene OE, independent of the amplified gene, as well as gene-specific effects that were dependent on the genetic background. Natural variation in the response to gene OE could be explained by several models, including strain-specific physiological differences, resource limitations, and regulatory sensitivities. This work provides new insight on how genetic background influences tolerance to gene amplification and the evolutionary trajectories accessible to different backgrounds.

Research Organization:
Univ. of Wisconsin, Madison, WI (United States)
Sponsoring Organization:
National Institutes of Health (NIH); USDOE; USDOE Office of Science (SC)
Grant/Contract Number:
SC0018409
OSTI ID:
1811587
Alternate ID(s):
OSTI ID: 1811588
OSTI ID: 1852646
Journal Information:
eLife, Journal Name: eLife Vol. 10; ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.Copyright Statement
Country of Publication:
United States
Language:
English

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