Previous Article |
Table of Contents
| Next Article 
BIOLOGICAL SCIENCES / GENETICS
Defining genetic interaction
*Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115; Department of Biochemistry, Stanford University, Stanford, CA 94305; Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294; Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada M5S 3E1; and ¶Center for Cancer Systems Biology, Dana–Farber Cancer Institute, 44 Binney Street, Boston, MA 02115
Communicated by David Botstein, Princeton University, Princeton, NJ, December 31, 2007 (received for review October 19, 2007)
Sometimes mutations in two genes produce a phenotype that is surprising in light of each mutation's individual effects. This phenomenon, which defines genetic interaction, can reveal functional relationships between genes and pathways. For example, double mutants with surprisingly slow growth define synergistic interactions that can identify compensatory pathways or protein complexes. Recent studies have used four mathematically distinct definitions of genetic interaction (here termed Product, Additive, Log, and Min). Whether this choice holds practical consequences has not been clear, because the definitions yield identical results under some conditions. Here, we show that the choice among alternative definitions can have profound consequences. Although 52% of known synergistic genetic interactions in Saccharomyces cerevisiae were inferred according to the Min definition, we find that both Product and Log definitions (shown here to be practically equivalent) are better than Min for identifying functional relationships. Additionally, we show that the Additive and Log definitions, each commonly used in population genetics, lead to differing conclusions related to the selective advantages of sexual reproduction.
epistasis | fitness | gene function
Author contributions: R.M., R.P.S.O., J.L.H., G.G., and F.P.R. designed research; R.M. performed research; R.P.S.O. and G.G. contributed new reagents/analytic tools; R.M. and F.P.R. analyzed data; and R.M. and F.P.R. wrote the paper.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/cgi/content/full/0712255105/DC1.
** Note that 
as defined in Study J differs from our Additive definition by a scaling factor. The same conclusions are reached using the definition of a from Study J.
||To whom correspondence should be addressed. E-mail: fritz_roth{at}hms.harvard.edu
© 2008 by The National Academy of Sciences of the USA
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg What's this?
