Re: An unanswered question

Perplexed in Peoria wrote:
"John Harshman" <jharshman.diespamdie@xxxxxxxxxxx> wrote in message news:F5Hrl.14094$D32.5352@xxxxxxxxxxxxxxxxxxxxxxx
CNCabej@xxxxxxx wrote:
Responding to my question of why a hypothetical change in a regulatory
sequence, would expand anteriorly expression of the Hoxc-8 gene (thus
determining the loss of forelimbs in pythons, on March 2, J. Harshman
wrote:

A new, deleted, or altered
transcription factor binding site will have a phenotypic effect only in
those cells in which that transcription factor is expressed. You are
exposing your profound lack of understanding of gene regulation and
regulatory networks. Again, I suggest you read one or more of Sean
Carroll's books. They present a basic understanding of these concepts,
essential if you are to carry on any meaningful conversation on development.
This explanation seems tautological to me for it gives no answer to my
question: Why expression domain of the transcription factor for the
gene expands anteriorly? I found no answer in the books he
recommended me.
Can anyone else knows the answer to my question?
Look, I don't know the actual details of this particular case. It may be that nobody does. But it's conceptually very simple, and hardly tautological. Let me make up a transcription factor. Let's say that transcription factor X is expressed in the average tetrapod from the region of the atlas to just caudally of the forelimb bud. And suppose that the Hox C8 promoter has a binding site for X, one that suppresses expression. That would mean that Hox C8 would not be expressed cranially of the forelimb bud. Now suppose that a mutation happens in the Hox C8 promoter that deletes the X binding site. X no longer binds to the Hox C8 promoter. Hox C8 expression is therefore no longer suppressed in the region of X expression, and so its region of expression expands. Note that this is the result of a single mutation in the promoter region of Hox C8. Neither X, nor its promoter, nor its expression pattern has changed in any way. Of course, this is only one of many ways in which mutations can alter expression patterns. Changes in X could also have changed the expression pattern of Hox C8, or changes of some gene upstream of X. I give only the simplest possibility here.

Note that this is a hypothetical example, purely to show you that such things are possible and to explain how they might work, since your claim was that a mutation can't alter tissue-specific expression patterns. Do you see now how it could?

In general, the expression pattern of one gene is determined by the expression patterns of other genes upstream in the regulatory network. There can be many genes influencing the expression pattern of any given gene, some of them activating it and others suppressing it. That's what a regulatory network is.


John, can you recommend a standard textbook which explains the kinds
of things covered in that last paragraph? Preferably one which covers
the *theory* of genetic regulation without getting bogged down in the
application of that theory to animal development.

No. I don't know of anything that discusses development without actual examples. That doesn't mean it isn't out there. I suppose you're not interested in texts that do mention real animals, but nevertheless, here's my favorite: http://seanbcarroll.com/books/From_DNA_To_Diversity/

I'm far from an expert on evo-devo. Most of my understanding comes out of a conference I went to 10 years ago and a few books I've read since. But I sure understand it better than the brassicalean fellow.

I'm afraid my understanding of biological control systems is only at the
level provided by General Biology or Molecular Biology textbooks.
I probably ought to read something a bit deeper and more specialized.


.

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