Teresa's S/O and G/O hypothesis: Resp2 to Robison

Keith Robison robison at mito.harvard.edu
Thu Mar 14 11:13:11 EST 1996

Teresa Binstock (binstoct at essex.UCHSC.edu) wrote:
: On 13 Mar 1996, Keith Robison wrote:
: > 
: > ste2 and ste3 belong to the G-protein coupled receptor (GCR) superfamily,
: > and large family used for many purposes including vision (rhodopsin).
: > 
: > Trying to draw a link between yeast mating and human gender determination
: > via GCR isn't particularly compelling; GCR's are ubiquitous.
: > 
: > Keith Robison
: > Harvard University

: Teresa responds: 

: 1. Belonging to a superfamily does not mean that all members of the 
: superfamily are functionally interchangable.

Of course not!  The point here is that finding that a GCR is 
involved in the immune system, and a GCR is involved in yeast 
mating, isn't terribly promising evidence for concluding that
the immune system is involved in human gender determination.

In other words, what I am saying is that you can conclude nothing
further than both systems have GCRs; _you_ are the one concluding
there is a special relationship between these particular GCRs.

: 2. ste2 and ste3 are membrane-spanning receptors and are not G-proteins, 
: but are linked to G-proteins (J Biol Chem 268.11.8070-7 1993).

Yes, that is the definition of GCR...

: 3. The fact that "GCR's are ubiquitous." (Robison, 1996) does not address 
: the rationale of Teresa's hypothesis regarding sexual- and 
: gender-orientations. 

No, you have it backwards.  I'm not saying your hypothesis is incorrect,
because GCRs are ubiquitous.  I'm saying that because GCRs are
ubiquitous _AND_ because you have not shown a specific relationship
_within_ the GCR superfamily between the immune system GCRs and
the yeast GCRs, that the GCR-connection is meaningless.  Your general
hypothesis may well be right, but the GCR-connection adds nada to it.

For example, yeast mating pheremones require an ABC-type transporter
for their export; and ABC-type transporters are critical to
immune cell function.  Does this evidence further support your 
gender determination hypothesis?

: 4. The link between ste2 and ste3 and human thymic epithelium is actual

Please point out a reference which shows a link between ste2/3 and 
human thymus GCRs; all of the citations you have listed appear to
be general to the family, or specific to ste2/3 without reference
to the human genes.  In particular, is there a special sequence
relationship (quick check says no)?  Can the human genes complement
yeast deficiencies?  What is it that makes you believe that there
is more than a familial connection between the two proteins?

Keith Robison
Harvard University
Department of Molecular & Cellular Biology
Department of Genetics 

robison at mito.harvard.edu 

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