I teach a genetics class and spend a lot of time explaining dominance
at the mendelian level compared to the molecular level. Two things
come to mind that might be relevant to the discussion.
What I try to get across to my students is that there are no simple
rules for predicting the molecular mechanism behind observed
inheritance patterns. To me, this is the fun part of genetics.
Genetics texts have a tendency to (figuratively) wave their arms
around when explaining mechanisms behind co-dominance, incomplete
dominance etc in the section on mendalian genetics, and never picking
up the same thread or examples when in later sections they discuss
molecular mechanisms of genetic traits. I try to give lots of
examples of molecular mechanisms behind various transmittance
patterns.
My favorite one is in the Klug and Cummings genetics text and
is different than the mechanisms I've seen posted on this subject.
Some genetic defects of collagen appear to be dominant by the
following mechanism: 3 identical polypeptide chains assemble into the
tropocollagen subunit. If one allele makes normal polypeptide chains
and the other makes defective chains, the dominance appears after
assembly of the tropocollagen. 1/2 of the chains are normal, 1/2 of
the chains defective. it only takes one defective chain of the three
in the tropomyosin subunit to result in abnormal collagen.
Therefore:
1/2 x 1/2 x 1/2 = 1/8 normal tropomyosin
which leaves 7/8 abnormal tropomyosin
So one/half mutant allele products leads to 7/8 defective collagen
which we would observe as dominant.
Another disease (one I used to work with) is an enzymatic
defect of heme biosynthesis called porphyria cutanea tarda. It is
caused by a variety of mutations which resulted in either no gene
product from the defective allele, or inactive gene product from the
defective allele. The disease was usually described in the
literature as autosomal dominant, but in reality it was much more
complicated. For one thing it was usually (prenatally) lethal when
homozygous but very occasionally people would live into adulthood,
but with more severe symptoms than the heterozygotes. Thus, the
disease was recessive for the severe phenotype but dominant for the
less severe phenotype (as in sickle cell disease vs trait). The
medical community got around this by giving the heterozygote form of
the disease a different name than the homozyous form of the disease.
Other complications were whether the heterozygous form of the disease
was incomplete dominance (true if the particular mutation resulted in
no gene product) or codominance (true if the particular mutation
resulted in inactive gene product). Also, most heterozygotes never
showed clinical symptoms, and could only be identified by molecular
or biochemical tests. The medical community just ignored all of this
complicated stuff and continues to call the disease an autosomal
dominant trait. I personally am not sure what you should call it,
but it certainly illustrates how mendelian and "neo" mendelian
concepts are usually simplifications of very complex processes, and
that even within one trait, there are often sub-traits caused by
different mutations. I think some new terminology will have to be
invented as we learn more about these kinds of things.
Jim Garey Duquesne University
