Teresa's S/O and G/O hypothesis: Resp3 to Robison

Teresa Binstock binstoct at essex.UCHSC.edu
Thu Mar 14 21:11:20 EST 1996


Teresa responds to Keith, with his beginning set forth in full for clarity:

On 14 Mar 1996, Keith Robison wrote in response to Teresa's Resp2:
> 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.
> 
> : Teresa's response to that post included: 
> 
> : 1. Belonging to a superfamily does not mean that all members of the 
> : superfamily are functionally interchangable.
> 
> Keith has countered:
> 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.

1. This paraphrase is such an oversimplification of the rationale central to 
my hypothesis. 

2. I most definitely have not "concluded" anything; I have offered a 
hypothesis -- based upon three specific molecules that at least by label 
are present in both yeast and humans (GnRH and "GnRH", ste2, ste3).
	Many yeast/human molecules are homologous 
and some from one species function in the other and vice versa. The immune 
system is known to differentiate self and not-self, and confusions of 
those two are often credited with part of the causality underlying 
autoimmune diseases. If, for example, ste2 and ste3 are functionally linked 
with self and not-self molecules (e.g., in immune cells within the nasal 
mucosa) then such networks may (hypothesis, NOT conclusion) comprise a 
mechanism whereby mating-type is determined (ie, sexual orientation). 
Additional autoimmune mechanisms that dysregulate self and not-self might 
also induce patterned responses that the organism (ie human individual) 
interprets as gender-identity other than his or her XY or XX chromosomes 
would otherwise induce. (See Keith's ABC Transporter notion hereinbelow).

> In other words, what I am saying is that you can conclude nothing
> further than both systems have GCRs. 

Based upon many yeast studies and the one study reporting human ste2 and 
ste3, I base part of my hypothesis on a "coincidence" far more specific, 
namely; not only do both systems have GCRs, but both humans and yeast
(according to the literature) have ste2 and ste3 molecules. 

> _you_ are the one concluding
> there is a special relationship between these particular GCRs.

I repeat, I am "concluding" nothing. In contrast, I am presenting a 
hypothesis; and yes, my hypothesis is partially based upon these two 
molecules and not upon more general characteristics of the superfamily.


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

> Keith: 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.

This is most interesting, because nowhere in my original postings of my 
hypothesis did I mention the GCR superfamily. I mentioned specific 
molecules and did not try to show "a specific relationship _within_ the 
GCR superfamily...[rest of quote in prior paragraph]." Invoking the 
superfamily was something that has emanated from Harvard; and I find 
myself agreeing with Keith Robison, "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?

Quite possibly. I've wondered whether or not non-secretion of self-type 
chemo-signal molecules might contribute to the person's sensing of self 
in relation to male-others and in relation to female-others. There may be 
other possible mechanisms as well. 


>Teresa: The link between ste2 and ste3 and human thymic epithelium is actual
> 
> Keith: 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.  

To quote Keith Robison (see above) the GCRs generalization seems to add 
nothing. Patel et al (J Clin Immunol 15.2.80-92 1995) specifically report 
finding STE2 and STE3 in the human thymic epithelium. Their study was a 
reporting of molecules found and was not a general treatise about one or 
more superfamilies nor was their study a gene-mapping exercise. All I know 
as a fact is that their abstract in medline and their actual published 
study report STE2 and STE3 as occurring in the human thymic epithelium.


> In particular, is there a special sequence relationship (quick check 
says no)?  

Sequence homologies in general are often reported amidst a range from 25% 
to 90% or more. I do not presume that human STE2,3 are exactly homologous 
to S. Cerevisiae ste2,3. Consider alpha-factor pheromone, which is 
described as a GnRH-like tridecapeptide whereas GnRH is a decapeptide. 
Yet when yeast alpha-factor is placed on mammalian gonadatropes, they 
secrete gonadotrophins. So, even if the structures of yeast and human 
ste2,3 are not quite identical, they still may have retained functional 
similarity.


> What is it that makes you believe that there
> is more than a familial connection between the two proteins?

I'd like instead to counter with a question. Given the clear sexual 
dimorphisms (i) of yeast, (ii) their a-factor and alpha-factor 
chemo-molecules, and (iii) their ste2 and ste3 chemo-signal receptors, 
and given also that ste2 and ste3 are reported as present in the human 
thymic epithelium, when did nature and/or God impose a different 
mechanism for the selection of appropriate mating-types? 

My sense of the literature is that no one has researched in domains 
near to those pointed towards by my hypothesis, and if there are any 
cites to the contrary, I'm very interested in knowing about them.


Teresa


Teresa C. Binstock, Researcher
Developmental & Behavioral Neuroanatomy
Denver CO USA
			Teresa.Binstock at uchsc.edu






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