Genomes, Epigenomes, and Genitals 

I’m a guy who enjoys having sex with other guys. There. I said it. Not exactly an earth-shattering fact about my personal life for those who know me — except for maybe my mom. (Hi, Mom! I’m gay, by the way.)

While I’m always captivated by shirtless men working out in the gym, I’m even more captivated by the question of why. Why am I gay? Why do I enjoy balls while my older brother enjoys boobies?

There’s evidence to support the claim that sexual orientation has a genetic component, but no scientist as of yet has discovered what is sometimes erroneously referred to as “the gay gene.” (Though, there are gay jeans: denim, tight fit, holes cut just below the back pockets.) But the claim that sexual orientation has a genetic component presents a few puzzles geneticists have been struggling to solve.

For example, there are numerous instances of identical twins — identical DNA, mind you — where one twin is gay and the other is straight. How can there be a genetic component to sexual orientation if identical twins with the same DNA play on different teams?

“What we do know is that there are regions of the genome that have repeatedly shown to be associated with sexual orientation,” says Dr. Tuck Ngun, a postdoctoral researcher at the David Geffen School of Medicine of the University of California, Los Angeles. “The most famous of these would be Xq28 — a small part on the X chromosome.”

But if there are identical twins with identical DNA where only one is homosexual, then what other biological factors are involved in determining sexual orientation?

There’s also the problem of homosexuality being at an evolutionary disadvantage. “One of the big questions is, ‘If sexual orientation is genetic, why hasn’t it been selected, or weeded out of the gene pool?’ If you’re gay, your chances of having a child are quite a bit lower than if you were straight,” observes Ngun.

From personal experience, I can tell you that we gays are not shy about passing our DNA onto others, but that’s certainly not the reason homosexuality remains a consistent trait in the human population.

Last year, working with the Center for Gender-Based Biology at the University of California in Los Angeles, Ngun authored a study looking to answer these questions. He took saliva samples from 37 pairs of twins where one was gay and one was straight, and he took saliva samples from another 10 pairs of twins who both were gay.

Ngun then examined differences in the twins’ epigenome to determine —

(Wait, epi-what? Epigenome. Stick with me here. I’m willing to bet you’re not a geneticist, but neither am I, so you’re in good company.)

Ngun examined the differences in the twin’s epigenome to determine if those differences were correlated with the twins’ sexual orientation.

“An algorithm using epigenetic information from just nine regions of the human genome can predict the sexual orientation of males with up to 70 percent accuracy,” reads the study’s press release.

Okay, there’s a lot to unpack here. After reading that last paragraph, you might even be sitting in a bar right now, vigorously scratching your head and asking that hot guy or hot gal next to you, “What the hell is epigenetics?” (This article would be a great conversation starter, by the way. You could get laid tonight. You’re welcome.)

Let’s start with defining epigenetics. Your epigenome is nothing more than chemical compounds attached to your DNA telling your genome what to do all the time — kind of like an overbearing husband or wife.

“The epigenome doesn’t change your DNA, but it decides how much or whether some genes are expressed in different cells in your body,” Hank Green explains on his YouTube channel, SciShow.

In his episode on epigenetics, Green uses the analogy of what he calls epigenetic punctuation — where the genome is like a paragraph, and the epigenome is like the punctuation in that paragraph. This means you can manipulate the meaning and interpretation of a sentence (the genome) using punctuation (the epigenome).

Take the two following sentences as an example:

Sentence one: Let’s eat, Grandma!

Sentence two: Let’s eat Grandma!

The words and syntax (word arrangement) in both sentences are identical, yet removing the comma in the second sentence changes the meaning dramatically … and promotes cannibalism — which is wrong. Don’t eat your grandma.

Now, if you compare the DNA of a pair of identical twins, their genomes (or their sentences) are the same, but differences in their epigenome (or their punctuation) can modify the expression of their identical, yet individual, genomes. This results in different traits expressed from identical DNA.

Using grammar to explain science! How cool is that?! (My English degree is finally paying off.)

Epigenetics can help explain why, with some pairs of identical twins with identical genomes, one is straight while the other is gay. It can also explain why some traits, such as homosexuality, continue to flourish while always being at an evolutionary disadvantage.

Ngun and his team picked up on 10 years of previous genetic research, diving into this question of sexual orientation and epigenetic variances in identical male twins. “When I came on board, the technology had matured quite a bit, so we decided to revisit this question of whether we see any differences based on sexual orientation in the epigenetic pattern.”

“All of this on the molecular level,” adds Ngun, “has only been done on male sexual orientation, so female sexual orientation remains really understudied.” (Get on in, geneticists!)

So now that we’ve got a handle on what the epigenome is, just how do these epigenetic compounds give instructions? Well, there’s a term for this process: DNA methylation.

(Methy-what? I know, I know. Stick with me.)

“Methylation helps to control how readily portions of the DNA are actually read and translated into proteins that actually affect traits that we observe,” says Jemery Yoder, postdoctoral research fellow at the Department of Forest and Conservation Sciences and the University of British Columbia.

Essentially, methylation is the process of your epigenome turning certain genes on your genome on or off.

“DNA methylation has been looked at in a lot of different contexts,” adds Yoder. “Developmental traits, for example, things like height and productivity in corn plants. Anything you can measure you can relate to which parts of the genome have been methylated.”

Ngun and his team compared the DNA methylation patterns of the twins in his study. “We took those patterns at each location at the genome — at position one we have a number for twin 1 that’s, let’s say, 20 percent methylated. And then in twin 2, it’s 50 percent methylated.”

Ngun then took those numbers (a gargantuan amount of numbers, mind you) and fed them into a computer algorithm to compare the different DNA methylation patterns.

“We trained the computer for us to be able to say, okay, this is what a typical straight methylation pattern is supposed to look like, and this is what a typical gay methylation pattern is supposed to like. Then we give it a set of new twins that it hasn’t seen before and try to get it to predict.”

And predict it did, calculating which twin was gay and which twin was straight with almost 70-percent accuracy, which is higher than the percentage you would get by guessing or just flipping a coin. “To our knowledge, this is the first example of a predictive model for sexual orientation based on molecular markers,” the study’s press release reads.

Essentially, the algorithm is a form of gaydar using epigenetic patterns to predict who is gay and who is straight. How cool is that!?

It should be noted that the conclusions drawn from this study are correlative, not causal. Ngun isn’t making the claim he found the biological cause to human sexual orientation. He didn’t find the gay gene.

And just like any other frontier science, there are caveats surrounding his findings. “The catch is that the authors of this new paper are working with a very small sample of people,” says Yoder.

“That tells us right off the bat that what they find is not likely to have a high degree of statistical competence.”

Yoder adds that the study would have to be repeated with possibly tens of thousands of test subjects in order to verify Ngun’s findings. “So we’ve got a ways to go.”

Ngun concedes that the sample size was small, but adds that garnering funds to acquire and test DNA samples from thousands of test subjects is problematic. “In the last few years, especially with increasingly tight budgets at the major funding bodies like the National Institutes of Health, it’s become all but impossible.”

Not surprisingly, money for genetic studies is usually funneled into research grants for institutions working to find cures to ailments such as heart disease or cancer. “Funding bodies are also very squeamish about anything to do with sex,” adds Ngun.

And to Ngun’s knowledge, there are no other geneticists who are looking at the link between the epigenome and human sexuality.

Another challenging variable in the study was the type of samples used (saliva) to find the differences in epigenetic patterns of the twins.

“The thing about epigenetic marks is they solve this basic biological problem,” says Yoder, “which is that every cell in your body has the code you need to make an entire human being, but not every cell in the body is an entire human being, right? Each cell has different genes turned on and off using these epigenetic systems to get to the combination of genes to be a nerve cell or a blood cell or a muscle cell.”

Yoder explains that looking at the differences in the epigenome of brain cells would provide more accurate and reliable data in trying to pinpoint which methylation patterns may contribute to differences in sexual orientation.

“Epigenetic marks that might make a difference in sexual orientation are going to be particularly noticeable in brain cells,” says Yoder, quickly adding, “to be fair, this is a hard thing to ask for.”

Indeed. I’m certainly not willing to have samples of my own brain tissue pulled out of my head through holes drilled into my skull. (Though, that might allow all my voices to escape.)

But despite his critiques, Yoder adds that Ngun’s work is a step in the right direction in finding a biological foundation for sexual orientation and development.

“When I first saw the headline [of Ngun’s study],” says Yoder, “my initial reaction was, ‘Oh good! Someone’s finally taking a look at this.’ I want to give these folks credit for at least taking a stab at things. This really is a line of inquiry that lots of people think is going to solve this puzzle.”

Ngun’s study has indeed assembled part of the puzzle by showing differences in the epigenetic patterns of identical twins where one twin is gay and the other twin is straight. These differences are so pronounced, that you can potentially predict the sexual orientation of an individual just by studying the epigenome.

In short, your very own epigenome could potentially influence who you end up sleeping with tonight. (Or more accurately, who you want to sleep with tonight, only to end up alone on the couch eating an entire pizza by yourself.)

Ultimately, studying our epigenome is more than just working to understand the biological machinery that drives our sexual development. This type of research bores deeper into fundamental questions of what makes us who we are as individuals — of why I prefer balls while my older brother prefers boobies.

“All the work has been done because we’re curious about why we are the way we are,” says Ngun. “Because sexual orientation, whether you’re gay or whether you’re straight, it’s such a fundamental part of your life.”

So for those who are still reading this article in a bar, stop being a coward and turn to that hot gal or hot guy sitting next to you and tell that person that your epigenetic pattern finds his or her epigenetic pattern super sexy.

And if you get laid tonight because you broke the ice with a discussion on epigenetics, you got laid because of science! How cool is that!?