Saturday, May 16, 2009

The "Gay Gene" Part III

In Part I, I presented a "single gene, single trait" model of sexuality. Simple, straightforward, black and white. In Part II, I presented a sample of the current literature on the biology of human sexuality. Not surprisingly, the current literature doesn't even come close to developing a complete biological model of how human sexuality works. The only conclusion science has reached at this point is that human sexuality is "governed" by several genes as well as environmental factors. Why is it so hard to pinpoint these factors?

In this post I will attempt to elucidate why it will be very difficult to develop anything nearing a complete biological model of human sexuality, at least in my lifetime. There will be terms and concepts that I'll try to explain in such a way that can be understood by non-scientists, but I apologize in advance if things start flying over your head. This is also a long post. You have been warned.
-----
Additive Alleles
The first concept is "additive alleles." Recall in Part I, I mentioned how alleles are different "versions" of a gene. When a trait is controlled by several or many genes, the alleles could have an additive effect on the trait.

Example: let's say there are 5 genes (genes A, B, C, D, E) that affect height. For each gene there are 2 alleles, an "upper-case" allele and a "lower-case" allele (i.e. A/a, B/b, C/c, D/d, E/e). Assume that each gene contributes equally to height, and that each upper-case allele contributes 3 inches to height and each lower-case allele contributes 1 inch to height. Thus, if an individual has alleles ABCDE, that individual will "gain" 15 inches total, whereas an individual with alleles abcde will "gain" only 5 inches.

In the example just given, each gene contributes in a completely additive fashion. However, each of the genes may very well have a different inheritance pattern and may contribute or otherwise affect the observed trait differently, such as one of the following.

Co-dominance
In co-dominance, different alleles of a gene are equally dominant and expressed at the same time.

Example: a plant has a gene that determines red/white flower color. The "red" allele and the "white" allele are co-dominant. Thus, a flower with both alleles will have red and white striped petals.

Incomplete Dominance
In incomplete dominance, the dominant allele does not completely "mask" the recessive allele. That is, some of the recessive allele "bleeds" through.

Example: a plant has a gene that determines red/white flower color. The "red" allele is dominant to the "white" allele. But because the "red" allele is incomplete dominant, a flower with both alleles will be pink.

Penetrance
Penetrance refers to the degree, or "likelihood," that an allele is expressed.

Example: a woman has the BRCA1 gene mutation that causes breast cancer. The BRCA1 mutation is 50-80% penetrant. Thus, that woman has a 50-80% increased chance of developing breast cancer.

Epistasis
In epistasis, one gene masks the effect(s) of another gene(s). That first gene is said to be "epistatic" to the other gene(s).

Example: 2 genes partly determine fur coat color in cats. Gene A is epistatic to Gene B. If a dominant allele of Gene A is present, then the fur coat color is black and Gene B is never observed regardless of what Gene B is. If only the recessive allele of Gene A is present, then the fur coat color depends on Gene B. Gene B produces either a white fur coat, an orange fur coat, or a white/orange striped fur coat depending on the alleles; again, Gene B can only be observed if only recessive alleles of Gene A is present.

Other
Topics I chose not to discuss include: variable expressivity, linkage, developmental pathways, biochemical pathways, cis-acting and trans-acting gene regulation, repressors, activators, maternal effect, and X-linked traits. To discuss all this would probably bore you all into oblivion.
-----
Now, to tie this all together. How might all the above apply to the biology of human sexuality? Well, to begin with, we know that the genes affecting sexuality must be additive in some fashion. Several genes "stack" their effects to influence a person's sexuality.

Let's say a gene is co-dominant for sexual orientation. Thus, for some guy, 2 copies of Allele 1 = straight, 2 copies of Allele 2 = gay, and 1 copy of each = bi. But bisexuality here might be a little strange, as that guy might find himself more attracted to females at one point in his life, and more attracted to males at another point in his life. The attraction might "alternate" between males and females, or depend on the situation.

Let's say a gene is incomplete dominant for sexual orientation. Thus, for some guy, 2 copies of Allele 1 = straight, 2 copies of Allele 2 = gay, and 1 copy of each = bi. Assuming both alleles give equal weight, a bisexual would find himself equally attracted to males and females.

Let's say having the dominant allele of a gene is 70% penetrant. Assume that the dominant allele represents heterosexuality. Thus, possessing 2 copies of the dominant allele = 100% straight, 2 copies of the recessive allele = 100% gay, and 1 copy of each = 70% chance of being straight and 30% chance of being gay.

Let's say there is a gene that is epistatic to the gene with incomplete dominance just mentioned. As long as there is a dominant allele of the gene the guy will be straight; it doesn't matter if the "incomplete dominance" gene would "make" a person straight/bi/gay. But if only the recessive allele of the epistatic gene is present, then sexual orientation would depend on the "incomplete dominance" gene mentioned above.

If there were multiple genes (well, there are), and all the inheritance patterns above are expressed at least once within this "set" of multiple genes, then this could easily account for the spectrum of human sexuality from straight to bi to gay. It could explain why some people who're bisexual associate more with being straight or gay, or how some people are attracted to women at one point in their lives and men later. The complexity stacks upon itself to yield a spectrum of results.

So far, this is a completely biological model that ignores environment, and yet it "can" explain everything. But how might environment play a role? How does the environment affect genetics? Through something called epigenetics.

In the end, just having the gene "for" something isn't enough. It must be expressed, or in other words, the gene must be turned on. Our genes turn on/off in response to environmental cues. The "environment" is a very broad term and can refer to: the air, the water, the food we eat, the uterine environment of the fetus, social and cultural factors, the people we meet, etc.

To put a more accurate twist or spin on the strictly biological model above, each of the genes affect one's tendency to be straight/bi/gay. Whether or not people actually become straight/bi/gay might depend on various environmental factors. Here things get tricky. It can be assumed that for most people, the genes are aligned such that the tendency to be heterosexual is overwhelming and the tendency to be homosexual is minimal. That is to say, that the tendency to be heterosexual is so great that it's nearly impossible for the environment to turn that person gay. The opposite may very well be true - a person's genetic alignment (genotype) may be so skewd towards being gay that the tendency to be gay is overwhelming, thus any attempts to be straight will almost certainly fail. In this sense, these people are truly "born straight" or "born gay."

But there is a huge gray zone between the extremes of either end. What about people in the "middle?" Their sexuality might depend on the circumstances that "trigger" certain genes to go into high gear. For example (I admit, not the best of examples), a cute boy (or girl) passes along, "flips" on this gene or that, and gets the ball rolling towards one direction or the other (or it may just stay put).

The "epigenome" is thought of as a genetic landscape of hills, plains, and valleys. On either extreme end is a deep valley, and it'll take a lot of genetics and environment to move a person out of the extremes. But between the extremes are hills, plains, and smaller valleys. Where a person is along this genetic landscape determines his/her sexual orientation. The environment merely moves that person along until the he/she settles in a valley.

If you have reached this point then totally pat yourself on the back, you've reached the end. I hope you can see just how complex the genetics of human sexuality can get, as well as how both genetics and environment probably play a role. And again, despite all this, this post is BARELY scratching the surface of how complex it actually might be, as it's just a model to demonstrate that it's not easy.

Please comment, ask questions, etc. ^_^ I'm always happy to discuss biology and particularly genetics, which I've sort of "specialized" in towards the end of undergrad and in my one year of grad school.

12 comments:

naturgesetz said...

Well, I'm not sure I understood it all, and I'm sure I couldn't repeat it all or pass a test on it without a lot of work. But it's pretty clear that it's not possible to say that all gay men were simply "born that way." More generally, it seems that any attempt to identify a single cause is doomed to failure.

But if something environmental can trigger a gene, can something else "untrigger" it once it has fired?

Aek said...

naturgesetz: Yes, identifying a single "cause" is doomed to failure. It's also pretty clear that some gay men are simply "born that way," though of course probably not all.

As for triggering, it depends. Some roads only lead one-way. For example, once a stem cell differentiates into a more specialized cell, it can't go backwards. If you shoved a heavy truck with broken breaks down a steep hill, it's going to take a lot of effort to stop it and push it back to where it came.

So too are these triggers. Not all are reversible. And while some "might" be reversible, the act of reversing might have unintended consequences (like the development of cancer when reverting a mature cell back into an embryonic state).

Tyler said...

wow.

despite being.... difficult to understand, your series on orientation has been really interesting!

i really like your blog :)

E said...

I sadly have nothing of substace to add. Kinda ashame being an ex-bio major and all.

billy said...

A genetic understanding of sexuality is basically a statistical analysis of allele frequencies. We're moving forwards when we start looking at epigenetics and the broader regulation of gene expression. But let's find out what the proteins actually DO in our bodies, how they influence biological structures and processes. I'm convinced this is the future of molecular biology, and genetics will be a powerful tool for this. When we do that we've got a chance of understanding behaviour in biological terms.

Aek said...

Tyler: Haha, kinda blows your mind, doesn't it? I know it's difficult to understand - that's how I felt when I first learned about it. But it's actually a really cool subject.

I'm glad you like my blog. ^_^

E: Awww, don't feel bad. A lot of bio majors don't focus on genetics and thus know surprisingly little about it.

billy: True, right now it's just at the statistical allele frequencies and genome-wide association studies (GWAS). But, that step is necessary to identify "candidate" genes that may play a role in what we're looking at.

Epigenetics is gaining in importance, as well as gene regulation. An amazingly small percentage of our genome actually codes for protein. Not that I'm saying that protein isn't important, but it might actually play a fairly small role.

Most RNAs are non-coding RNA (i.e. they don't code for protein), and we're just now figuring out what they do. Perhaps it's not the proteins that we should look at, but the RNA, and how to turn on/off that RNA or the DNA that makes it. There's only one way to find out, and that's to do it!

Sasha (Malchik Gai) said...

Wow, intelligence is sexy. This is fascinating stuff. I'm happy that I can actually follow it too. :)
Stopped by to say, I wish your B-day had been better. I've had a few less than stellar ones myself.
Hugz
Sasha

Aek said...

Sasha: Hi! I'm glad you're able to follow it, I try. :P

Thanks for the b-day wishes!

Sasha (Malchik Gai) said...

Pleasure to make your acquaintance.
To be honest I just barely kept up with it, but I think I got the gist;P

And, It's the only polite thing to do.
Have a great holiday weekend

Aek said...

Sasha: Haha, I had a feeling that's how it's going to go. Thing is, genetics is very difficult to describe in words, much better to do with visuals.

If ever you're confused, I'm sure Wikipedia offers some enlightening tidbits.

Have a great holiday weekend yourself! :)

B said...

Hey Aek, been a while, but I'm still around. I am very impressed. A lot of thought went into this! I've thought about how homosexuality might develop too, though usually I focus on environmental and psychological factors while just assuming there's "some genetically determined propensity". :-) Genetics is fascinating, but I only took one class on it in college. Maybe I'll have to look into it more in grad school . . .

Aek said...

B: Hi! I'm glad you're still around. ^_^ You should look into genetics when considering grad school. The genetics field is increasing so rapidly it's ridiculous!

Hey, we should chat sometime or something. I'll email you just to say hi. :P