This past spring, I did an interesting project on the last twenty years of research into the genetic basis of homosexuality. It was a really interesting project. I was an English major while in college, as I’ve said before. Because of this, I’m used to interpreting literature and constructing arguments based on fictional narratives, not scientific articles based on empirical data. It’s a very different mode of thought. I thought I would share some of my findings on here.
The genetic basis of homosexuality among humans, particularly in males, has been a controversial topic of much scientific debate, due to the fact that it seems to be a Darwinian paradox. In short, it should lessen the fitness of any individual who has it.
So how does it persist as a trait?
While it has proven difficult to isolate a specific gene as responsible for homosexuality in human males, there are plenty of data that supports its heritability.
There are two specific studies that I looked at that explored the possibility of homosexuality as an inherited trait. The first was a study done in 1993 by a team of colleagues headed up by a Dr. Hamer entitled “A Linkage Between DNA Markers on the X Chromosome and Male Sexual Orientation3.” As the title implies, Hamer’s team did find some linkage between male sexual orientation and specific markers located on the X chromosome, but we’ll get to that in a moment. The first thing that Hamer worked on was establishing the heritability of the trait. Using pedigree analysis (meaning by studying family lines and percentage of people with the trait), the study found that the rate of homosexuality was higher for males in the maternal line and that there was an absence of transmission through the paternal line. Furthermore, because the homosexual males shared inherited genetic information with uncles and cousins that were raised in various environments, it indicated that the trait was not influenced by rearing environment.
The second study that supports the heritability of homosexuality in the maternal line was one done by Dr. Camperio-Ciani et. al.2 in 2004. This research went a step further though, and found that there was a probability that the trait may have been selected for through a connection to an allele for female fecundity (by examining number of maternal offspring).
Now, while the heritability has been well established with this and similar research, the location of genetic markers has remained elusive. I looked at two particular studies here where the evidence was conflicting. Hamer’s research was the first, since his study was done in two parts. First, he established the heritability using the method above, then he used linkage analysis in order to statistically determine related genetic information in 40 homosexual sibling pairs. In the end, his team isolated 5 genetic marker loci that were statistically associated on the Xq28 region of the X chromosome. This was hailed at the time as a discovery of a “gay gene” by overzealous journalists.
In 1999, George Rice4 and his team attempted to repeat the results (with slightly revised methods). He and his team performed the same kinds of molecular analysis as did Hamer on 4 markers on Xq28 in 52 homosexual sibling pairs. In short, they failed to find any genetic markers statistically associate with sexual orientation on the Xq28 region of the chromosome.
So, with this kind of conflicting evidence, where do we go from here? How does this conflict get resolved? This is where we have to get creative in developing testable models for future research.
A study by Bocklandt1 is currently researching how genetic markers can be turned on or off by a process called methylation. Bocklandt’s research is attempting to find out what kinds of switches might lead to the expression (or lack of expression) of homosexuality as a trait.
At the same time, there is this really interesting epigenetic model of sexual canalization explored by William Rice’s team5. This model emphasizes the idea of “epi-marks,” inherited epigenetic modifications that direct or “canalize” sexual development. In this case, the trait itself is not inherited as a gene or genetic marker. Instead, the “epi-marks” are passed on, which lead to the expression of the trait.
How can we use these ideas to direct further research then?
In my opinion, we should broad W. Rice’s model of epigenetic tags (“epi-marks”) and apply it to methylation. These epi-marks have the potential to be heritable (but are not passed on every time), and could influence gene expression by using methylation to switch certain lines of code, containing genetic markers related to homosexuality, “on” or “off.” Concomitantly, if there are numerous genetic markers that contribute to the trait, then different combinations of switched “on” markers could produce the trait (similar to a polygenic trait).
To take this just a bit further, the co-occurrence hypothesis, mentioned in Camperio-Ciani’s research, could help with this. For example, if either the epi-marks themselves or the genetic markers were passed on with the allele(s) for other traits (like fecundity), then it would support Hamer’s conclusion, providing the impetus for natural selection to occur. This could conceivably explain how Rice and Hamer might come up with different results.
It’s clear that homosexuality is not a simple Mendelian trait. It’s likely the result of complex genetic inheritance added to epigenetic and developmental effects. Because of this, I doubt any single hypothesis will be likely to find a “primary cause” for the persistence of homosexuality as a trait. Instead, we have to be willing to look at a number of factors: genetics, epigenetics, intrauterine development, rearing environment, etc. Researchers should be working together along these lines to understand the multi-faceted, complex tapestry of human sexuality.
1: Abrams, M. (2007). The Real Story on Gay Genes. Discover Magazine. Retrieved from http://discovermagazine.com/2007/jun/born-gay
2: Camperio-Ciani, A., Corna, F., & Capiluppi, C. (2004). Evidence for maternally inherited factors favouring male homosexuality and promoting female fecundity. Proceedings of the Royal Society of London B, 271, 2217-2221.
3: Hamer, D.H., Hu, S., Magnuson, V.L., Hu, N., & Pattatucci, A.M.L. (1993). A Linkage Between DNA Markers on the X Chromosome and Male Sexual Orientation. Science, 261, 321-327.
4: Rice, G., Anderson, C., Risch, N., & Ebers, G. (1999). Male Homosexuality: Absence of Linkage to Microsatellite Markers at Xq28. Science, 284, 665-667.
5: Rice, W.R., Friberg, U., & Gavrilets, S. (2012). Homosexuality as a Consequence of Epigenetically Canalized Sexual Development. The Quarterly Review of Biology, 87, 343-386.