> To: molecular-evolution at net.bio.net> From: JEThomas at ix.netcom.com (Jonah Thomas)
> Subject: Re: dominant/recessive genes
> Date: 18 Nov 1995 07:43:22 GMT
> In <79347319DB at mercury.uark.edu> DRHOADS at MERCURY.UARK.EDU ("Douglas
> Rhoads") writes:
>> > From: JEThomas at ix.netcom.com (Jonah Thomas)
>> >> An organism that could change genes from dominant to recessive and back
> >> could possibly evolve faster. A gene that's currently favorably
> >> selected could spread faster if it was dominant. A gene that's common
> >> but currently unfavorably selected would do less damage if it was
> >> recessive. Also it would survive in the population longer, giving a
> >> greater chance that it would still be present if sometime later it
> >> became favorable.
>> >I am not sure this argument or hypothesis could ever hold water.
> >Organisms don't change from dominant to recessive or back, traits do.
>> Yes, I misspoke.
>> >Clearly a phenotype can be modified by the environment and the
> >penetrance can change with changing environmental pressure just as
> >the effects on `fitness' can change. Normally, a gene that is
> >unfavorably selected (what ever that means) will NOT be common unless
> >the population has just come out of a situation where the gene was
>> That's right. For an unfavorably selected gene to be common it must be
> only recently unfavorable. This can happen due to an environmental
> change that makes a previously-less-fit alternative allele more fit, or
> it can happen when a new mutation happens to be more fit. Both of
> these may happen fairly often.
>> >>Modifying genes that affect dominance would have to
> >>evolve at each location, and the selection that would lead to their
> >>evolution is weak. If they mutate at the same rates as the genes
> >>whose dominance they modify, they have little effect on selection.
> >>It doesn't work.
>> >Modifying genes that affect dominance do NOT have to be linked to the
> >gene. Why should they?? And what point are YOU trying to make?
>> Ah, why should they be linked. OK, let's look carefully at that.
> First, both Fisher and I suppose there is a general mechanism to affect
> gene expression. A gene that's turned on, makes something that
> eventually results in mRNA that produces a specific protein. A gene
> that's turned off has that process interrupted so the protein is not
> produced. Fisher and I both suppose that mechanisms exist which use
> this mechanism to produce dominance. There is more here than the
> simple model which says that recessive genes never produce a functional
> protein. In this model a recessive gene may produce a protein when
> it's homozygous, but that production gets shut off when the dominant
> allele is present.
But why look for some weird kind of interactions unless you just want
to find out whether you can envision some form of gene interaction
and then go out and find that it has or does occur in nature. Most
dominance-recessive interactions have to do with altered proteins
rather than RNA expression.
> Here it comes: Could you select such a dominance-modifying gene based
> on its effect on dominance? And the answer is, with reasonable
> assumptions it's hard to select such a gene if it is unlinked to the
> gene it affects. It is only selected when the version it makes
> dominant is selected relative to the version it makes recessive. This
> is a transient condition. When either allele is rare there isn't much
> selection for the modifier. When the modifying gene is rare there
> isn't much selection for the modifier. And after the dominant version
> increases its frequency, the only way to get another pulse of selection
> in favor of the modifier is to first select the other direction to get
> the frequency back down. This is not an effective way to breed
> modifying genes. It doesn't work.
But modifying genes would either be transcription factors that
regulate the gene or proteins that interact with the protein product
of the gene. In my opinion the transcription factor modifiers may be
less attractive because they will have multiple genes that they
regulate. However, there could be variant transcription factors and
therefore when these _unlinked_ genes come in contact (through a
cross) with a particularly susceptible allele then you can have an
altered penetrance/recessiveness. For multi-polypeptide complexes
and their interactions in penetrance/recessiveness one would look for
compensating (i.e. suppressor) mutants.
> But if the modifying gene is closely linked to the modified gene, then
> whenever the allele it modifies is selected, the modifying gene
> hitch-hikes. If it can make that gene dominant then they both increase
> frequency faster. When the allele it modifies is unfavorable, they
> both are selected against, and if it can then make that gene recessive then
> they both lose slower. (For clarity -- I'm not suggesting that every copy
> switches from dominant to recessive at the same time. I'm suggesting that
> a few copies get switched at random, and selection increases their
> numbers relative to the others.)
>> Also here's a handwaving molecular argument -- if there's a general
> mechanism to modify a closely-linked gene, it can be applied to any
> gene merely by translocation. If modifiers have to evolve separately for
> each gene, they don't get so much flexibility and won't arise so often to
> be selected.
>> >What if the modifying gene was pre-existent in the population. Multi
> >enzyme complexes and receptor signaling process already exist and all
> >upstream and downstream processes would have variants in the
>> Yes, but that isn't what I'm talking about. I don't want to propose a
> specific molecular mechanism for dominance-change because 1st, I could
> make a silly molecular mistake that would get it laughed at, and 2nd,
> the reality could be some completely different molecular mechanism that
> gave an equivalent result. But here's a start toward something like
> that: Say you have an intron that has a part that can flip over at a
> fairly high rate, say once per thousand individuals. When it is in
> state A, during transcription it splices out a part that can interact with
> the same intron in state B. Once the part is spliced out, the hnRNA the
> intron is inserted into works normally.
>> The intron in state B works the same way exactly, except that when the
> spliced-out RNA from a transcript of A (or a product of that RNA, etc)
> interacts with it, it doesn't splice out the same way but instead puts
> an ealy stop signal into the mRNA. Both versions result in functional
> protein, but the state-B intron results in nonfunctional protein from
> the state-B allele whenever the state-A version is present.
>> This intron could evolve once and then get spliced into a wide variety
> of genes. Versions of it might get selected at whichever sites they do
> a good job.
>> >> But if dominance-modifying genes could be transposed to different
> >> locations at a relatively high rate, they would need to evolve only
> >> once. And if they switch from dominant to recessive and back at a
> >> relatively high rate, say an order of magnitude or two below the
> >> selective rate, they could be selected.
>> >HUH?? (see above)
>> I hope this is clearer. The dominance-modifying gene needs to be
> linked to the modified gene to be selected with it. It's plausible
> that molecular mechanisms might be possible that would do direct
> dominance-modification of closely-linked genes in a single standard
>> What I haven't shown at all, is that there is selective advantage
> in expressing only one of a pair of heterozygous alleles. If almost
> every time organisms do as well or better expressing both, then the
> selection that might drive my hypothetical mechanism won't be there and
> the whole thing collapses. Never mind that it's possible, without that
> selection, it probably won't happen.
>> So what's the truth? I think only molecular studies can tell. I have
> a Just-So story that seems to me at least as plausible as the standard
> one, the one which says that recessive genes simply produce
> dysfunctional proteins. I can make mathematical models and computer
> simulations which predict that under the right circumstances my
> hypothetical dominance-modifiers would be selected. I can't tell whether
> those circumstances arise, without real-world data which I think is not
> available yet. There is likewise no real-world data available to test
> the standard Just-So story.
So are you arguing that the sickle cell hemoglobin gene is
dysfunctional??? On the contrary it is very functional it is just
that in certain contexts it is considered `bad' while in other
contexts it is good. It is a variant and has varying degrees of
penetrance depending on the environment (high altitude vs sea level,
interactions describedis not
||Doug Rhoads || Dept. of Biological Sciences||
||drhoads at mercury.uark.edu || 601 Science Engineering ||
||drhoads at uafsysb.uark.edu || University of Arkansas ||
||501-575-3251 || Fayetteville, AR 72701 ||
|| My Dogma Just Got Run Over by Someone's Karma ||