Gay genetics

Sunday 31st May 2009
Submitted by JV Chamary
Gay Gene

“WANTED! Gay Men with a Gay Brother,” reads the banner. It’s held aloft by Dr Alan Sanders and a group of colleagues from NorthShore University near Chicago who are attending a gay pride festival. They’re recruiting volunteers for a groundbreaking study that sets out to answer fundamental questions about who we are.

“We’re trying to locate genes that may influence variation in male sexual orientation,” Sanders says. Volunteers from over 700 families responded. Researchers asked them questions about their sexuality, the size and structure of their families, and took DNA samples. Sanders is now analysing that data and the results could tell us once and for all whether there’s such a thing as a ‘gay gene’.

“The people participating in our study are interested in contributing to this kind of scientific knowledge and want to understand at least part of how they came to be the way they are,” Sanders says. 

The search for ‘gay genes’ goes back to 1993, when a US team led by Dr Dean Hamer described a region of DNA located on the X chromosome called Xq28. The region also goes by another name: GAY-1, a genetic marker linked to male homosexuality. 

The discovery caused Hamer to be attacked from all sides. “Conservative, right-wing people hated it because they felt that it was saying that being gay is like being black, that it was in-born, that it would somehow ‘excuse’ gay people or give them more rights,” says Hamer. “On the other hand, gay people hated it too because, at that time, there were fears that the discovery would be misused to abort gay babies and wipe gay people off the face of the Earth.”

Although these fears remain, in recent years the search for ‘gay genes’ has become more accepted by the gay community, in no small part because a biological explanation would undermine arguments that being gay is a social or lifestyle choice. Conservative attitudes remain unchanged, however. “They continue to be vehemently opposed to any notion that homosexuality is something natural,” says Hamer. 

Despite their objections, there’s a lot of evidence that homosexuality has a biological basis. While there hasn’t been much research on lesbians, there has been on gay men. For instance, identical twin brothers (siblings derived from the same fertilised egg) are more likely to both be gay than fraternal twins (twins that develop from separate eggs). The fact that identical twins have the same DNA and fraternal twins share 50 per cent suggests that male homosexuality is hereditary.

The gay gene

It was scrutinising family trees to see how homosexuality is inherited that led Hamer to the discovery of Xq28. Now chief of the gene structure and regulation section at the US National Cancer Institute, his study revealed a curious pattern: gay men tended to have more gay uncles and gay male cousins on their mother’s side of the family than on their father’s. 

“For geneticists that’s fascinating because it suggests it could be due to X chromosome linkage – those types of traits tend to run on the female side for males,” says Hamer. This is because males inherit their X chromosome from their mother. 

To track down the DNA region linked to the gay trait, Hamer used a technique called ‘linkage mapping’, an approach that lets geneticists find a gene even when they don’t know what it does or where it’s located. Linkage mapping works because close relatives like brothers share not only a particular trait, such as homosexuality, but also the genes underlying the trait. When comparing bits of DNA from two brothers, the sequences will, on average, be the same 50 per cent of the time. So, if you study many pairs of gay brothers and find a DNA region that’s the same in more than 50 per cent of cases, it’s likely to be linked to homosexuality. In this case, Hamer compared the X chromosomes from 40 pairs of gay brothers, and Xq28 stood out. 

Inheriting the gay version of Xq28 won’t necessarily make you homosexual. “Our studies showed that it significantly increased the odds of being gay, but it was not determinative,” says Hamer. “Many people who are gay don’t have any history of homosexuality in their families.” He points out that some heterosexual men in his 1993 study also had the so-called gay gene. A subsequent study in 1999 failed to replicate Hamer’s results and other researchers are sceptical that Xq28 is linked to homosexuality at all.

Big brothers, immune mothers

Many scientists believe that exposure to hormones during pregnancy heavily influences sexuality. Hormones are chemical messengers, released by certain cells to affect the growth and development of other cells in the body. During pre-natal development, for example, the sex organs in a foetus can recognise testosterone, which will switch on genes to make it male.

Aside from a few superficial differences (among them penis and ring-finger length – both longer in homosexuals), gay and straight men’s bodies appear the same. The exception is homosexual men’s brains, which show remarkable similarities to the brains of heterosexual women, suggesting that sexual orientation depends on the effect hormones have on the developing brain. 

But these two factors only go so far in explaining how homosexuality develops. “People assume that all of the biological influence on sexual orientation is either genes or hormones,” says sexologist Ray Blanchard from the University of Toronto. “They might account for the lion’s share of variance in sexual orientation, but it looks like there’s some other bit that requires a third biological mechanism.” 

In 1996 Blanchard and Professor Tony Bogaert revealed a peculiar phenomenon: the more older brothers a boy has, the greater their chances of being homosexual. This ‘fraternal birth order effect’ meant that each subsequent brother increases the odds of being gay by 33 per cent. An only child has a two per cent chance, but with 10 brothers the odds are over 20 per cent. But why the increasing odds? Blanchard believes it’s related to how a mother’s body protects itself when pregnant with a son. 

“There’s only one system in the mother that would have the ‘memory’ to know how many male foetuses she’s previously carried: the immune system,” says Professor Blanchard. According to his theory, a mother’s immune system keeps track of the number of sons she’s already had, producing antibodies to protect her against male-specific proteins entering her bloodstream, which often occurs during childbirth. As the mother’s level of immunisation increases with each son, so too do the chances of variation from typical sexual orientation as, in theory, the mother’s antibodies could cross the placenta and neutralise proteins that her son needs for normal sexual development.   

Many of these male-specific proteins are found on the Y chromosome, DNA that’s foreign to females. “A lot of male-specific proteins are preferentially expressed in the testes and have a crucial role in sperm development,” says Blanchard. “Some are expressed in the foetal brain for reasons that no-one has established, but you wouldn’t expect them to be expressed without a reason.” 

Blanchard believes that homosexuality is “100 per cent biological”, and estimates that the fraternal birth order effect accounts for 15-30 per cent of gay men in the population. So what explains the rest?

Fertile females

Professor Andrea Camperio Ciani at the University of Padova in Italy has tested various hypotheses by studying 100 families of gay men. Not only did he replicate Blanchard’s birth order effect, he also detected inheritance of homosexuality on the mother’s side, supporting Hamer’s idea of a gay gene on chromosome X. The maternal inheritance effect seems most important too. 

“Genetics explains 20-25 per cent for the moment,” says Camperio Ciani. “The rest is unknown. A part is environment; a part can be other genetic elements that we cannot perceive with our study.” In principle, the genetic component might even be the Xq28 region. 

Regardless of which regions of DNA are linked to homosexuality, the very existence of ‘gay genes’ creates a Darwinian paradox. How would genes that cause homosexuality pass from one generation to the next, given that gay people reproduce less than heterosexuals? Natural selection opposes anything that might cause even a small reduction in the number of offspring you produce, so a gay trait would soon disappear from the gene pool. “If you carry a trait that reduces your fecundity [the number of offspring you produce] by 10 per cent, in seven to eight generations your trait and all your descendents disappear,” says Camperio Ciani. 

The paradox was finally resolved by his 15-year-old daughter. After Camperio Ciani described the observed patterns in pedigrees of homosexuality – the effects of maternal inheritance and birth order – his daughter suggested that he re-check his data to see if the female relatives of gay men had more children on the mother’s side. When Camperio Ciani went back to the lab, that’s exactly what he found. “Mothers and aunts on the maternal line of homosexuals had around one-fifth to one-fourth more kids than the heterosexual comparison, and also than the paternal line.” 

He thinks that the evolution of homosexuality is driven by a process called sexually antagonistic selection. It’s where a genetic factor confers an advantage when expressed in one sex, but incurs an evolutionary cost in the other. In this instance, the ‘gay genes’ don’t exist to make men homosexual, instead they’re a consequence of ‘fertility factors’ that help women reproduce.  

Nipples are another example of a sexually antagonistic trait: they’re needed for feeding babies, but developing nipples in men is a waste of the body’s resources and allow errors leading to breast cancer.

The search for sexuality

Even if Camperio Ciani’s fecundity factors are the same as Hamer’s gay genes, it doesn’t tell us what the specific genes actually do. Hamer speculates the genes might boost the size or connections from parts of the brain used in reproduction – such as the hypothalamus – to make people more libidinous. 

Alan Sanders’s study at NorthShore University could finally reveal the identity and function of ‘gay genes’. Sanders, director of the Behavior Genetics Unit, is comparing DNA from gay brothers to find shared genes that underlie sexual orientation. He’s initially using linkage mapping to find candidate regions. The large sample size – over 700 families – provides huge statistical power for detecting regions significantly linked to homosexuality. Sanders will then use sequences from databases like the Human Genome Project to pinpoint which genes are in these regions. 

So what happens if ‘gay genes’ are found? While they may confirm the idea that homosexuality has a biological basis, many people fear that the results could be used to discriminate against gay people. “It is a valid concern,” says Sanders. “People we talked to at gay pride festivals have designer-baby kind of worries – a genetic test employed in a pre-natal way, or for employment and insurance discrimination, maybe in the military too. It’s not just an issue in sexual orientation, but intelligence or disease screening .” 

A test for gay genes also has a flipside: homosexual couples might exploit reproductive technology to have gay kids. “This has been a huge debate in other areas, like deaf parents wanting to have deaf children,” says Hamer, who has fathered a daughter with a woman from a lesbian couple. “One of them said, ‘If I had my choice, I’d select the sexual orientation of my child’. But this is all theoretical for now, as it’s not actually happening yet.” 

Genes that influence our sexual orientation further fuel the debate over what makes us who we are. For Hamer at least, sexual orientation is determined at birth. “It’s mostly biological,” he says. “The way a person acts is altered by culture, society and individual choice, but that’s a different issue than the underlying deep-seated orientation.” 

Dr JV Chamary is reviews editor of Focus


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