Unless you are specifically writing a paper on the history of the theories
I would not worry too much about Fisher's theory the generality of which has
been discredited (Orr, 1991: PNAS 88,11413). Wright called the alternative the
"physiological" theory, but I think a better term is the "dose-response"
theory. As Joe Felsenstein points out, Muller and Haldane were in on the act.
I believe it was Haldane who first got to grips with dominance in metabolic
terms (1930; Am. Nat. 64, 87), but he like Fisher thought that weak selective
evolutionary forces would act at the heterozygote level. Muller, I believe was
the first to postulate evolutionary selection acting at the homozygote level.
Thus (1932;Proc. 6th Int. Cong. Genet. 2, 213-255) he postulated "that the
mutations favouring dominance....have been selected and are maintained, not so
much for their specific protection against heterozygosis at the locus in
question, but as to provide a margin of stability and security, to insure the
organism against weakening or excessive variability of the character by other
and more common influences- environmental and probably also genetic".
So take a dose response curve:
Pheno-* * * * * * *
type * * A B
* * * * * * * * * * *
Dose of Gene Product (proportional to gene dose)
If the homozygote has a dose equivalent to a point on the plateau of the
dose-response curve (B) it has excess if its normal needs (assuming it does not
want to make the dose of its product rate limiting). Now along comes an
"extreme environmental disturbance" which reduces (say) transcription so that
the dose of gene product falls. Since the normal level is in excess there is a
margin of safety, so that even if the concentration falls to point A, there is
still sufficient to maintain function (without the dose of the gene product
itself becoming limiting). So this selective force will favour the survival of
organisms which have the margin of safety. Thus a heterozygote, with half the
dose of the gene (and hence half the dose of gene product) will still have
sufficient product (equal to point A) for function in normal circumstances.
Only when the extreme environmental disturbance arises will the heterozygote be
at risk. The big question is what is the extreme environmental disturbance? Is
it one thing or multiple things? In a paper which has been submitted for
publication, I argue that the extreme environmental disturbance in unitary..it
is the heat-shock response.
Please send me your first born child at your earliest convenience.
Sincerely, Don Forsdyke