Re: [MLUG - DISCUSSION] For Fruit Flies, Gene Shift Tilts Sex Orientation

[Jonathan King <EMAIL:PROTECTED>]

On 6/6/05, Mike Miller <EMAIL:PROTECTED> wrote:
> I remember that some of you have expressed interest in genetics of
> homosexuality before.  This new work was done in Drosophila melanogaster,
> but the findings should have implications for how we think about sexuality
> in every animal species....
> 
> http://taxa.epi.umn.edu/bgnews/2005/msg00128.html

Well, maybe.  This paper (I've read it, but not very thoroughly) is
important, but maybe not exactly because what it says about sexuality
per se.  This is one of those important papers that tests a clear
prediction of our current understanding, but, frankly, one of the
predictions I suspect a lot of people would have thought might be
wrong.

In a nutshell, we know a lot about the genes that are responsible for
two aspects of fruitfly sex: physically being male or female, and
acting in accordance with your sex.  In brief, the way this happens is
this:

Female fruitflies have 2 X chromosones, while males have just one.
On the X chromosome is a gene with the colorful name "Sex lethal"
(Sxl) which is the key to fruitfly sex determination.  (The name comes
from the fact that if an embryo has zero copies of the gene, it dies
before much development happens.)  Given two copies of Sxl, female
flies actually get a working version of the protein through a
mechanism I'll skip.  Males don't get this.  What Sxl does is tell
another gene, called "transformer" (tra), how to operate.  If Sxl is
functional, transformer will be translated into a female-only version
of the gene, which is functional.  What transformer does is two
things.  One thing it does is (indirectly) tell a gene called
"doublesex" to generate a female sex organs, coloration, etc.  When
transformer doesn't do anything (like in males), doublesex tells a fly
to generate male sex organs, coloration, and other manly stuff in a
fly. Another thing transformer does is switch OFF the expression of
*one* kind of protein produced by the so-called "frutiless" gene. The
version of fruitless (fru for short) that gets turned off is the one
that specifies a male identity of the central nervous system and one
pair of muscles involved in the male's role in copulation.  The male
identity of the CNS triggers a series of male-specific behaviors
during the life of the fly.  In brief, a male CNS should recognize
females as possible mates and try to court with and mate with them. 
Similarly, female anatomy should trigger courtship in flies with a
male CNS.

What the authors did in the paper that's gotten press this week is
genetically engineer flies whose copy of the fruitless gene is exactly
like the normal one, except that you can't turn off the "I think like
a male" version of fruitless in the CNS.  So what you get here are
normal male flies, and female fruitflies whose CNS has assumed a male
identity.  What this means, in turn, is that the female flies are
attracted to normal female flies and try to court them.  Further, when
male flies try to court *them* (they look and smell like females and
have female sex organs, after all) the female flies "tell" the males
to get lost, just like any normal male would do.  (Normal male flies
have to do this since when they are really young, they look and smell
more like virgin females than fully mature male flies, and mature
males will try to have sex with anything that could be female.)

So the striking thing here is that the paper just validates what we
thought might be true in fruit flies IF ONLY we could generate females
with a male CNS.  But now we can do that, and the theory turns out to
be true: in flies, there are separate genes that specify anatomical
sex and sexual behavior, and you can create females who are
"anatomically correct" but neurally "wrong", in the sense that they
act like males in situations where males and females act differently.

This is important...but things are more complicated than that.  For
starters, sex determination in mammals including humans works in a
very different way; there's no guarantee that you'll have a genetic
pathway as clean as the one you get in fruitflies.  Further, while
there is pretty clearly a sizable genetic contribution to sexual
identity in humans, humans and their sex lives are *way* more complex
than what you see in a fruitfly.  And more strikingly, this paper
comes on the heels of others that show you can get some degree of
"masculinization" of fruitfly behavior through genetic pathways that
don't have anything much to do with the "fruitless" gene...I could go
on, but only Mike Miller is reading this far, so I won't. :-)

Gosh; if that made sense, then I'm pretty proud of myself. :-)

jking

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