Box 2 Muller’s classes of mutations
In 1932 Hermann J. Muller described a system for classification of mutations based on functional criteria (Muller 1932). Muller’s classification and terminology remain valid today and are applicable to both mutations and overexpression phenotypes.
HypermorphA mutation that causes a gain of a wild-type function, such as hyperactivity or unregulated activity toward a normal target.
AntimorphA mutant allele that antagonizes its coexpressed wild-type gene product, resulting in reduction of total activity. Over the last two decades the term dominant negative has been used synonymously with antimorph. The term antimorph was coined by Muller on the basis of formal genetic tests and in the absence of any molecular information about gene structure or function, whereas Herskowitz’s dominant negative terminology (Herskowitz 1987) arose in an era when identification of protein domains in cloned genes, construction of specific mutations or deletions, and the ability to overexpress the mutant gene came under the investigator’s control, providing mechanistic insights into Muller’s antimorphs. Overexpressed mutants are not necessarily all antimorphic, however, but can also be hypermorphic or neomorphic.
NeomorphA mutation that causes a gain of an abnormal function, such as an enzyme targeting a new substrate, a DNA-binding protein obtaining altered binding specificity, or a protein localizing to an abnormal location.
HypomorphPartial loss-of-function mutation that results in reduced activity