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theories of dominance

Keith Robison robison1 at husc10.harvard.edu
Thu Mar 25 18:21:42 EST 1993

Thinking about dominance on molecular terms is interesting, but I believe
it is only useful when you already know the molecular picture.  Consider
the following:

Situation I

	Dominant wild-type allele
	Recessive mutant allele

	Frequent molecular explanation:  
	1) Functional allele makes product, 
	and can make up for 1 non-functional allele.

Situation II
	Dominant mutant allele
	Recessive wild-type allele

	Frequent molecular explanations:  
	1) Dosage of this gene is critical
	and is related to copy number.  Hence, one good copy will not
	suffice (many developmental genes fall into this category)
	2) E.g. retinoblastoma:
	a non-functional allele has a dominant tumor phenotype because
	the odds of a somatic mutation inactivating the wild-type
	suppressor are high.  Because the "screen" involved (tumor
	growth) is very sensitive, we detect these somatic mutations.
	3) The mutant is a gain-of-function allele altering
	the properties of the gene but does not destroy them.
	Perhaps the new allele binds more tightly than before to another
	molecule, or perhaps it binds something else.  Or, perhaps it
	has lost a functional site required for regulation (some
	oncogenes fall into this category -- mutations cause them
	to be stuck on).
	4) Mutant gene product "poisons" the system.  An example is
	resistance to streptomycin in prokaryotes -- resistance is
	generated by mutant ribosomal subunits which cannot bind
	antibiotic.  Wild-type ribosomes stall on the mRNA in the
	presence of antibiotic, and act as road-blocks for mutant
	ribosomes.  Another frequent example is if the gene product
	forms a homodimer -- wild-type/mutant dimers may be non-functional.

Hence, knowing how things are dominant/recessive (or co-dominant) will
not necessarily tell you much at the molecular level in itself.  More 
likely, once you know the molecular picture you can predict the
dominance of various mutations.  Dr. Bradshaw makes a good point
that dominant--recessive systems often appear to be co-dominant when
viewed from a different viewpoint.  

toby at stein.u.washington.edu (Toby Bradshaw) writes:

>In article <BRIANF.93Mar24160949 at dna.uvm.edu> brianf at dna.uvm.edu (Brain Foley) writes:

>>Many students in molecular genetics are confused about what "dominant"
>>and "recesive" mean.  Most often, recessive means that some gene
>>product is lacking, so if a cell-cell hybrid is made, the cell with
>>the dominant phenotype provides the lacking enzyme.  But this is not
>>always the case.

>OK.  It's late and my memory isn't the best.  I'm having a hard
>time coming up with an exception to the above.  Care to help me

See Situation II, sub-cases 3 and 4.  

>>I think that "dominant" can be a fuzzy term in some cases now.

Dominance is a very explicit term, but using it requires carefully defining 
the system you are discussing and it's boundaries.  For example, suppose
I am speaking of sickle-cell anemia.  Wild-type "S" is clearly dominant
over mutant "s" at sea-level, but at high-altitudes they are co-dominant
(and I suppose at really low oxygen partial pressures the dominance
reverses).  At the molecular scale, however, you could argue that
in terms of producing hemoglobin S and s are _always_ co-dominant --
presence of an S allele does not _prevent_ generation of s-type chains.
Put another way, do you define phenotype as the health condition or
what you might see on a gel?  

Keith Robison
Harvard University
Department of Cellular and Developmental Biology
Department of Genetics / HHMI

robison at biosun.harvard.edu 

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