> Reply-to: ANDERSOJ at gm1.nigms.nih.gov ("Anderson, James")
> To: "bionet.metabolic-reg mail newsgroup"
> <bionet-news at daresbury.ac.uk> Subject: Recent article in
> Nature
>>> The Feb 15 Nature (vol 379: 597) includes a review, "From DNA
> Sequence to Biological Function" by Stephen Oliver. The author
> proposes that the complete yeast DNA sequence (due momentarily) will
> trigger new strategies for the discovery and analysis of complex
> gene function. He states that some approaches to determining
> functional hierarchies "rests on the principles of metabolic control
> (or "flux") analysis." And, in particular, on "top-down"
> approaches. Could someone flesh this assertion out for me, a
> non-expert in MCA? I assume that he's simply drawing a conceptual
> parallel of MCA to proposed functional gene analysis, but is there
> an real, or experimental relationship as well?
>> Jim Anderson
>
Well the basic idea is straightforward. All the genomes that have been
sequenced are seen to have ORFs that code for genes of unknown
function. Since the expression of these genes must have observable
metabolic concequences when they ARE expressed (and their evolutionary
concervation suggests that they ARE 'important') the assumption would
be that genes organising or participating in the same BIT or 'area' of
metabolism (imagined as an n-dimensional Koch-Light-type chart that we
all have on our lab walls) are likely to tend to have effects on
metabolic fluxes that are more similar to each other than genes
participating in or controlling DIFFERENT bits of metabolism. The
degree of similarity could lead to a classification much as in
conventional taxonomy. The top-down notion as applied here merely
recognises that for practical as well as conceptual reasons it may be
helpful to 'lump together' certain segments of metabolism.
Of course the task then is to solve the inverse problem and go from
metabolism to gene, starting, presumably, with genes of KNOWN
function.
I personally have my doubts as to how appropriate any SPECIFIC
taxonomic analogy or grouping is likely to be, especially in the
face of pleiotropic effects (and given what goes on in taxonomy one
may suppose that there will be numerous different opinions), but the
problem is of tip-top importance (both scientifically and for things
like discovering new antibiotic targets as bugs become resistant to
all the present ones) and this is really the only game in town at the
moment.
Hope this helps,
Douglas.
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