Re: Doogie Mice
Fri, 3 Sep 1999 12:34:06 EDT

In a message dated 9/2/99 7:26:57 PM Pacific Daylight Time, writes:

> On Thu, 2 Sep 1999 wrote:

> > Mutations to regulatory regions do not need to be specific at all.
> > As a rule, most mutations in regulatory regions will either
> > increase or decrease expression.

> I don't think we disagree here. What I was trying to say was that
> they have to be *specific* for increases in expression. Changing
> a GC to a CG may increase expression, while changing a GC to an AT
> may decrease expression.

OK, I understand that point. But given that most genes have multiple regulators there will be several potential targets. Six regulatory regions with 2 potential mutations each gives 12 targets. If any are negative repressors that goes up.

With a successful wild herbivorous species, you will have hundreds of thousands of individuals for hundreds of thousands of generations. Even at a typical mutation rate of 10 per billion nuceotides per generation, each mutation will recur hundreds or thousands of times. So there have been plenty of memory upregulator mutations for natural selection to play with. From an evolutionary viewpoint, it's not rare at all.

Availability of mutations is an issue for top carnivores and geographically restricted species but we're talking mice here :-)

>> many regulators are repressors.

>I think we would have to discuss this more carefully. While
>in bacterial genomes I might agree that repressors tend to be
>more common, I suspect that in higher organisms, promoters
>would tend to be the dominant factors.

Currently we do know of more eukaryotic promotors than repressors, but there are still lots of repressors. That's all I said. My textbook actually claimed that virtually all eukaryotic regulators were promotors but when I went to the literature to look at the evolution of regulation I found that wasn't the case.