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theories of dominance

bishopj at botany.washington.edu bishopj at botany.washington.edu
Tue Mar 23 14:46:12 EST 1993

	The recent post objecting to the physiological explanation of dominance  
based on a relatively new appreciation of the complexity of gene regulation and  
action (objection reprinted below) is intriguing, but does not prove its point.  
The post seems to raise two types of objections.  The first is that a wide  
variety of mutations or regulatory processes can affect gene expression, and  
that "inactivation" of an enzyme may occur in a variety of ways (change in  
kinetic parameters, change in concentration of enzyme, etc.). 	  
	Kascer and Burns (1981) show that Wright's approach to explaining  
dominance was essentially correct in its recognition that a sequence of  
chemical reactions, such as in a metabolic pathway, tend to be buffered against  
variation in any one reaction.  They also show why this occurs, i.e. why the  
relationship between enzyme activity and the flux of product is non-linear (as  
drawn in Don Forsdyke's post and copied below) and why the wild type is on the  
plateau of the curve. They assume that a wide variety of mutational events can  
alter catalytic activity, and describe the catalytic consequences of mutational  
events in terms of equivalent changes in enzyme concentration. I don't see how  
the more detailed knowledge of gene regulation which Foley describes changes  
Kascer and Burns' conclusion, that recessivity is "a necessary consequence of  
the interactions inherent in the kinetic organization of enzyme systems."  BTW,  
Kascer and Burns conclude that these interactions ARE  the "margin of safety"  
or "safety factor" which Muller and Wright argued were necessary.  Thus the  
safety factor is already present and does not need to be selected for.

Pheno-*              *  *  *  *  *  *
 type *           *  A              B
      *        *
      *     *
      *  *
      *  *  *  *  *  *  *  *  *  *  *
                Dose of Gene Product (proportional to gene dose)

	Foley's other objection seems to be that there are loci which exhibit  
overdominance (the heterozygote has higher fitness, or metabolic flux than  
either homozygote) or incomplete dominance (one homozygote has higher fitness  
than the heterozygote or other homozygote),  or where different genotypes  
perform differently in different environments ("conditional fitness").  With  
regards to types of dominance,  overdominance is not commonly found.  
Furthermore, among mutations arising in a population recessivity is clearly the  
rule.  Genotype by environment interactions (or conditional fitness) certainly  
could have important effects on mutations, such as maintaining a higher number  
of alleles at a locus than otherwise expected, but how does it affect the  
physiological explanation of dominance?
	In fairness to Brian Foley, this thread has emphasized the historical  
foundations of dominance theory, rather than its present form.  That kind of  
discussion always leaves me wondering "what do we know NOW?" too.

Some references to check out:
Kacser, J. and J.A. Burns.  1981.  The molecular basis of dominance.  Genetics  
97: 639-666.
Keightly, P.D. and H. Kacser. 1987.  Dominance, pleiotropy, and metabolic  
structure.  Genetics 117: 319-329.

Relating metabolic flux to variation in quantitative characters:
Keightly, P.D.  1989. Models of quantitative variation of flux in metabolic  
pathways.  Genetics 121: 869-876.


John Bishop
Department of Botany
University of Washington, Seattle
bishopj at botany.washington.edu

In article <BRIANF.93Mar22182029 at dna.uvm.edu> brianf at dna.uvm.edu (Brain Foley)  
> 	It seems to me that many theories of dominance and other such
> theories are now a bit outdated.  We now know a lot more about gene
> regulation, chromosomal inactivation via methylation, and other
> phenomena to know that there is more to the story than just two
> alleles both producing an equal amount of protein.
> 	I work with a gene that shows codominance in one cell type and
> dominance in others.  In fact, the codominance is just scored as
> dominance unless you use radioctivity to detect the actual level of
> production in the heterozygote.  Their are so many ways to make two
> alleles of a given gene.  One could have a defect in the promoter, so
> that the different alleles make different amounts of an identical
> protein.  One could have a stop codon in the reading frame,
> eliminating the protein production.  One could have an alteration in
> the Km, the Kd or the Kcat of an enzyme.  THe list is endless.
> 	Thus, the theory that covers all cases is hard to come by.
> There are many genes that increase an individual's fitnes only when
> present in the heterozygous state.  There are many that provide

> "conditional fitness" (they help an individual living in some
> conditions but not the same individual if it lives in different
> conditions).  There are many that are detrimental if two functional
> copies are not present.  
partial, or incomplete dominance?

>There are many that are detrimental if two
> functional copies are present.
deleterious recessives?

> --
> ********************************************************************
> *  Brian Foley               *     If we knew what we were doing   *
> *  Molecular Genetics Dept.  *     it wouldn't be called research  *
> *  University of Vermont     *                                     *
> ********************************************************************

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