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Genetics, Vol. 174, 5-15, September 2006, Copyright © 2006
doi:10.1534/genetics.106.064550
Sometimes the Result Is Not the Answer: The Truths and the Lies That Come From Using the Complementation Test
R. Scott Hawley*,
,1 and
William D. Gilliland*
* Stowers Institute for Medical Research, Kansas City, Missouri 64110 and Department of Physiology, University of Kansas Medical Center, Kansas City, Kansas 66160
1 Corresponding author: Stowers Institute for Medical Research, 1000 E. 50th St., Kansas City, MO 64110.
E-mail: rsh{at}stowers-institute.org
It is standard genetic practice to determine whether or not two independently obtained mutants define the same or different genes by performing the complementation test. While the complementation test is highly effective and accurate in most cases, there are a number of instances in which the complementation test provides misleading answers, either as a result of the failure of two mutations that are located in different genes to complement each other or by exhibiting complementation between two mutations that lie within the same gene. We are primarily concerned here with those cases in which two mutations lie in different genes, but nonetheless fail to complement each other. This phenomenon is often referred to as second-site noncomplementation (SSNC). The discovery of SSNC led to a large number of screens designed to search for genes that encode interacting proteins. However, screens for dominant enhancer mutations of semidominant alleles of a given gene have proved far more effective at identifying interacting genes whose products interact physically or functionally with the initial gene of interest than have SSNC-based screens.
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