Re: Genes and Development Conference

Kevin O'Brien (
Sat, 3 Apr 1999 17:05:39 -0700

>I've seen similar statements peppering the literature as well.
>There's no doubt that some believe it (or did believe it at one
>time). However, I think the when backed into a corner and really
>probed on the specifics, even those people quoted would probably
>admit that their comments were a tad overstated (I'd hope). What
>I find to be foolish are attempts to quantify what proportion of
>developmental control is genetic or "extra-genetic". They're
>*both* important. You can't have one without the other. I think
>that if someone (anyone) sits still and thinks about the problem,
>this becomes apparent. Genes are just parts of the whole organism.
>Take the example of cloning, where a nucleus is transferred from
>one cell type into another, which "resets" the developmental clock
>in the process. What changed? Probably not the DNA sequence. DNA
>is simply one of the many intermediate players in the whole process.
>The reason there has been so much focus on genes is that they are
>much easier to study. (Sequencing is easy, understanding the
>context is hard).

Forgive my ignorance (I work with proteins, not genes), but by extra-genetic
components are you referring to the cell's metabolic system, or to
extracellular protein factors, both or neither?

>This problem is not confined to development, but runs across
>areas like metabolism as well (Heck, if we're going to assign
>claims of priority, people studying metabolism recognized the
>problem very early). Knowing gene sequences aren't going to tell
>us all we need to know about how cells sense and respond to changes
>in their environments. We understand that metabolism is regulated
>at many levels in a huge interconnecting network of which genes
>are just one component.
>For example, there are now many technologies that allow us to
>monitor changes in the levels of the different mRNAs in a cell.
>We can subject a culture to various changes in conditions
>(nutrient availability, temperature, addition of antibiotics &
>etc.) and see which genes are activated or repressed in response.
>The hope is that with this information, one would be able to
>determine what functions/genes are involved in a particular response
>and figure out how the signals propagate through metabolism. The
>harsh reality is that so much change happens that it's practically
>impossible to distinguish signal from noise. Worse still, it's
>likely that the signals you're interested in propagated long before
>any response is reflected as a change in mRNA levels. On top of
>and woven within the "genetic program" are many other layers of
>"non-genetic" responses. (Aside: The technology still has its uses,
>specially in well-defined systems or in situations where you'd like
>to test a particular hypothesis).

This I do know something about; most of my research involves metabolic
systems. Most of the people I have worked with agree that genetic
regulation of metabolism is somewhat limited and crude; more like turning a
light on and off. Much of the "noise" you refer to above is the action of
the metabolic system trying to adjust to these gross changes. As such,
while we are interested in knowing if any genes are activated or shut down,
we concentrate more on the changes in the metabolic system itself -- what I
believe you call the "non-genetic" responses -- which are broader, more
subtle and more finely regulated, like a reostat. In our experience there
have been times when genes shut down and we expected a particular metabolic
activity to decrease, but it actually increased instead. And we've seen the
reverse happen as well. So we pretty much conclude that genes as less
important to overall metabolic control than the way the different pathways
cooperatively interact.

>BH> Just to check if one had to really dig for such quotes, I took
>BH> a look at <The Shape of Life> by Rudolf A. Raff. All I had to
>BH> do was look in the index under "gene" and then the subtopic
>BH> beneath "assuming primacy in developmental biology" which led
>BH> me to the following:
>BH> "Genes are important because they are the controllers and
>BH> executers of developmental processes." -- Raff
>Yes, taken at face value, Raff's statement is ridiculous. Genes
>can't execute anything.

By this you mean they need a metabolic system to first transcibe the gene,
then translate it into a protein or enzyme that then exerts the control or
executes the appropriate function, no?

Kevin L. O'Brien