In article <robison1.733101702 at husc.harvard.edu> robison1 at husc10.harvard.edu (Keith Robison) writes:
[snip]
>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.
I thought of this example, but it is a straight case of tumor
formation recessive to tumor suppression. Germ-line homozygotes
get bilateral retinoblastoma, and the heterozygotes can become
homozygous as you note above, usually only getting a tumor in
one eye. Maybe the phenotypes of heterozygotes and homozygotes
would lead a classical geneticist to conclude that the alleles
are codominant, measured by the number of eyes with tumors :)
(hard to justify a smilie in cases of childhood tumors leading
to blindness, it's just there to reinforce Keith's point that
phenotypes can be a poor guide to the molecular details).
> 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
^^^^^^^^^^^^
Hey, even my mother doesn't call me "Dr." :)
>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
>>out?
>>See Situation II, sub-cases 3 and 4.
I don't really think that sub-case 3 is an exception. The
recessive "not neoplastic" phenotype is due to lack of a
dominant allele for "neoplastically transformed". Sub-case 3
is different from the most common cases of dominance only in
that the mutant allele is dominant to the wild-type. The same
argument applies to sub-case 4, as far as I can tell, with
streptomycin sensitivity dominant to resistance. The recessive
phenotype, resistance, is due to lack of a gene product (the wild-type
ribosomal protein), and a cell fusion (or mating) experiment would give
you the answer as to which is dominant, as Brian has suggested.
>>>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?
Toby Bradshaw |
Department of Biochemistry | Will make genetic linkage maps
and College of Forest Resources | for food.
University of Washington, Seattle |
toby at u.washington.edu |
