In the three
simple two-allele systems described above, the biochemical
expression of the alleles in the heterozygote is exactly intermediate between
the two homozygotes. However, in each of the cases the
resultant pattern of phenotypic expression is
different. The variant alleles are in consequence described as dominant
or recessive, depending on the phenotype of the heterozygote
relative to that of the two homozygotes. The level of enzyme activity relative to the
++ "wildtype", or the nature of the phenotype (in
these examples, 'darker' or 'lighter'), or any
perceptions about "normal" versus "abnormal" are absolutely
irrelevant.
Biochemical expression in
diploids is most simply modeled as the additive result
of two alleles, each of which produces 50% of the total
enzyme activity. The standard phenotype of a homozygous genotype
is thus the result of the expression of two fully functional
alleles that produce 50% + 50% = 100% of the standard
activity. Then, a heterozygous genotype with a functional allele
and a non-functional allele produces 50% + 0% = 50% of
the standard activity. The phenotype of the heterozygote will
then depend on the degree of haplosufficiency
of the single functional allele. That is, does a single
functional allele provides sufficient enzyme activity
such that a standard phenotype is obtained? As it happens, for
most gene loci this is the case: the functional allele can then
be described as "dominant" to the non-functional
allele. Though the non-standard allele contributes reduced
or no activity, the standard allele still contributes its
standard amount, such that net activity in the heterozygote is
unchanged. Thus is most cases, the functional allele can be
described as "dominant" to the non-functional
allele. In those cases where a single functional allele does not
provide sufficient enzyme activity to produce the phenotype
when it is homozygous, that allele is described as haploinsufficient. The standard
alleles can then be described as 'recessive" to
the non-functional allele, which is therefore dominant.
Other circumstances
influence the phenotypic expression of heterozygous genotypes. "Up-regulation"
of gene expression in a heterozygote may compensate for the
non-functional allele by increasing transcription of the
alternative allele, such that the amount of enzyme
produced approaches that of the homozygous genotype.
Contrariwise, the presence of a defective protein may interfere
with the activity of the standard protein, e.g., by competitive
binding of substrate such that the standard enzyme cannot
convert it to product [this happens in Tribbles]. In
other cases, presence of a defective protein itself produces a
dominant phenotypic effect, notably accumulation of protein
plaques in the tri-nucleotide
repeat diseases. Finally,
recall that mutations in the promoter region may
either increase or decrease gene transcription, without
producing detectable allele variation in the protein-coding
region.
On this understanding, "dominant"
and "recessive" are simply short-hand
terms to describe the interactions of alleles underlying
production of a molecular or other phenotype. The fundamental
limitation of Classical Genetics, in the absence of an
understanding of the functional operation of Genes as DNA sequences,
was to treat dominance relationships (dominant, recessive,
semi-dominant, co-dominant, etc.) as intrinsic
properties of genes rather than as epiphenomena involving
the creative use of upper- and lower-case letters.
[Homework: What do I mean by that last phrase?]