Biology and sexual orientation

Sexuality researchers are often interested in homosexuality because there is evidence from twin studies that there is a biological involvement. Yet homosexuality does not appear to be adaptive from an evolutionary standpoint because homosexual sex does not produce children.

Although a number of biological factors have been considered by scientists, such as prenatal hormones, chromosomes, polygenetic effects, brain structure and viral influences, no scientific consensus exists as to how biology influences sexual orientation.

Most scientists agree that it is unlikely that there is a single "gay gene" that determines something as complex as a homosexual orientation, and that it is more likely to be the result of an interaction of genetic, biological and environment factors. However, in the fly Drosophila melanogaster, mutant alleles of the fruitless gene causes male flies to court and attempt to mate exclusively with other males.

Sexual orientation and evolution

Sexual practices that significantly reduce frequency of heterosexual intercourse significantly decrease the chances of successful reproduction, and for this reason, they would appear to be maladaptive in an evolutionary context following a simple model of Natural Selection. Maladaptive traits will only be removed from a population if the trait is under simple, direct selection, if it derives from a heritable component of a genotype and if the intensity of selection is greater than other evolutionary forces like genetic drift, or inclusive fitness. The prevalence of homosexuality does not, therefore, represent a problem for genetic or evolutionary theory.

Some have suggested that homosexuality is adaptive in a non-obvious way. By way of analogy, the allele (a particular version of a gene) which causes sickle-cell anemia when two copies are present may also confer resistance to malaria with no anemia when one copy is present.

TThe so-called "gay uncle" theory which developed posits that people who, themselves, do not have children may nonetheless increase the prevalence of their genes in future generations by providing resources (food, supervision, defense, shelter, etc.) to the offspring of close relatives. This "gay relative" hypothesis is an extension of the theory of kin selection. Kin selection was originally developed to explain apparent altruistic acts which seemed to be maladaptive. The initial concept was suggested by J.B.S. Haldane in 1932 and later elaborated by many others including Maynard Smith and West Eberhard . This concept also was used to explain certain social insects where most of the members are non-reproductive.

The primary criticism of this theory has to do with the fact that children share on average 25% of their genes with their uncles and aunts, but on average 50% with their parents. This means that to be adaptive, a "gay uncle" would need to save from death (or other lineage-terminating events) on average two nieces or nephews for every one of their own offspring they give up. Critics of the theory find this trade-off to be unlikely to produce a net reproductive gain.

Empirical studies

Twin studies

Researchers have traditionally used twin studies to try to isolate genetic influences from environmental or other influences. Unfortunately, many early twin studies in this area selected from non-representative samples, and gave non-representative results. Later twin studies have drawn from broader, more representative samples, and have given more representative results. A recent large-scale twin study, done by researchers at Yale University and Columbia University, concludes that "there is no evidence for strong genetic influence on same-sex preference in this sample."

Earlier twin studies gave indications that male homosexuality was genetically mediated. One common type of twin study compared the monozygotic (or identical) twins of people possessing a particular trait to the dizygotic (non-identical, or fraternal) twins of people possessing the trait. Since monozygotic twins have the same genotype (genetic makeup) while dizygotic twins share only, on average, 50% of their genotype, a difference in the prevalence of the trait in question between these types of twins provides evidence of a genetic component.

A few such studies began to examine homosexuality in the early 20th century, using small, non-random samples.

Bailey and Pillard (1991) in a study of gay twins found that 52% of monozygotic brothers and 22% of the dizygotic twins were concordant for homosexuality. Bailey, Dunne and Martin (2000) used the Australian twin registry to obtain a sample of 4,901 twins. Self reported zygosity, sexual attraction, fantasy and behaviours were assessed by questionnaire and zygosity was serologically checked when in doubt. MZ twin concordance for homosexuality was found to be 30%.

Criticism of these earlier studies included: recruitment through gay media (which may result in higher response rates from twins who are both gay), and recruitment from twin registries (which may result in higher response rates from twins who act more similar to each other). Bearman & Bruckner (2002), by contrast, based their conclusions on a study drawn from a wide population. The assessment of these researchers is:

Among [identical] twins, 6.7 % are concordant [that is, both express same-sex romantic attraction]. [Fraternal] twin pairs are 7.2% concordant. Full-siblings are 5.5 % concordant. Clearly, the observed concordance rates do not correspond to degrees of genetic similarity. None of the comparisons between [identical] twins and others ... are even remotely significant. If same-sex romantic attraction has a genetic component, it is massively overwhelmed by other factors.

Estimates of heritability for male and female homosexuality derived from a number of twin studies are shown below.

Estimates of heritability of homosexuality

Study	Male	Female
Hershberger, 1997	0%	48%
Bailey et al., 2000	30%	30%
Kendler et al., 2000	28–65%
Kirk et al., 2000	30%	50–60%
Bearman et al., 2002	7.7%	5.3%

Conclusions

Twin studies have received a number of criticisms including "ascertainment bias" where homosexuals with gay siblings are more likely to volunteer for studies.

Another issue is the recent finding that even monozygotic twins can be different and here is a mechanism which might account for monozygotic twins being discordant for homosexuality. Gringas and Chen (2001) describe a number of mechanisms which can lead to differences between monozygotic twins, the most relevant here being chorionicity and amniocity. Dichorionic twins potentially have different hormonal environments and receive maternal blood from separate placenta. Monoamniotic twins share a hormonal environment, but can suffer from the 'twin to twin transfusion syndrome' in which one twin is "relatively stuffed with blood and the other exsanguinated". If one twin receives less testosterone and the other more, this could result in different levels of brain masculinisation.

Overall, data appear to indicate that genetic factors may play some part in the development of sexual orientation, even if only a modest part. Further work is needed to more precisely quantify any genetic contribution to sexuality and to elucidate its mechanism.

Studies of brain structure

A number of sections of the brain have been reported to be sexually dimorphic; that is, they vary between men and women. There have also been reports of variations in brain structure corresponding to sexual orientation. In 1990, Swaab and Hofman reported a difference in the size of the suprachiasmatic nucleus between homosexual and heterosexual men. In 1992, Allen and Gorski reported a difference related to sexual orientation in the size of the anterior commissure.

However, the best-known work of this type is that of Simon LeVay. LeVay studied four groups of neurons in the hypothalamus, called INAH1, INAH2, INAH3 and INAH4. This was a relevant area of the brain to study, because of evidence that this part of the brain played a role in the regulation of sexual behaviour in animals, and because INAH2 and INAH3 had previously been reported to differ in size between men and women.

He obtained brains from 41 deceased hospital patients. The subjects were classified as follows: 19 gay men who had died of AIDS, 16 presumed heterosexual men (6 of whom had died of AIDS), and 6 presumed heterosexual women (1 of whom had died of AIDS).

The AIDS patients in the heterosexual groups were all identified from medical records as intravenous drug abusers or recipients of blood transfusions, though only 2 of the men in this category had specifically denied homosexual activity. The records of the remaining heterosexual subjects contained no information about their sexual orientation; they were assumed to have been mostly or all heterosexual "on the basis of the numerical preponderance of heterosexual men in the population."

LeVay found no evidence for a difference between the groups in the size of INAH1, INAH2 or INAH4. However, the INAH3 group appeared to be twice as big in the heterosexual male group as in the gay male group; the difference was highly significant, and remained significant when only the 6 AIDS patients were included in the heterosexual group. The size of the INAH3 in the homosexual male brains was similar to that in the heterosexual female brains. However, he also found some contrary results:

• Three of the 19 homosexual subjects had a larger group of neurons in the hypothalamus than the average control-group subject.
• Three of the 16 control-group subjects had a smaller group of neurons in the hypothalamus than the average homosexual subject.

William Byne and colleagues attempted to replicate the differences reported in INAH 1-4 size using a different sample of brains from 14 HIV-positive homosexual males, 34 presumed heterosexual males (10 HIV-positive), and 34 presumed heterosexual females (9 HIV-positive). They found a significant difference in INAH3 size between heterosexual men and women. The INAH3 size of the homosexual men was apparently smaller than that of the heterosexual men and larger than that of the heterosexual women, though neither difference quite reached statistical significance.

Byne and colleagues also weighed and counted numbers of neurons in INAH3, tests not carried out by LeVay. The results for INAH3 weight were similar to those for INAH3 size; that is, the INAH3 weight for the heterosexual male brains was significantly larger than for the heterosexual female brains, while the results for the gay male group were between those of the other two groups but not quite significantly different from either. The neuron count also found a male-female difference in INAH3, but found no trend related to sexual orientation.

Conclusions

LeVay concluded in his 1991 paper that "The discovery that the nucleus differs in size between heterosexual and homosexual men illustrates that sexual orientation in humans is amenable to study at the biological level, and this discovery opens the door to studies of neurotransmitters or receptors that might be involved in regulating this aspect of personality. Further interpretation of the results of this study must be considered speculative. In particular, the results do not allow one to decide if the size of INAH 3 in an individual is the cause or consequence of that individual's sexual orientation, or if the size of INAH 3 and sexual orientation covary under the influence of some third, unidentified variable."

He later added,

"It's important to stress what I didn't find. I did not prove that homosexuality is genetic, or find a genetic cause for being gay. I didn't show that gay men are born that way, the most common mistake people make in interpreting my work. Nor did I locate a gay center in the brain. ... Since I look at adult brains, we don't know if the differences I found were there at birth or if they appeared later."

In addition to this, of the men LeVay used in his studies, the sexual histories of the "heterosexual" men were unknown.

It is not clear from the research how HIV/AIDS may affect brain structure, a possible confounding factor. So rather than showing that differences in the neuron indicate homosexuality, LeVay's study may be showing that HIV/AIDS causes differences in neurons. It should be noted, however, that neither LeVay nor Byne found an HIV-related difference in INAH3 size.

Chromosome linkage studies

In 1993, Dean Hamer published findings from a linkage analysis of a sample of 76 gay brothers and their families. Hamer et al. (1993) found that the gay men had more gay male uncles and cousins on the maternal side of the family than on the paternal side. Gay brothers who showed this maternal pedigree were then tested for X chromosome linkage, using twenty-two markers on the X chromosome to test for similar alleles. Thirty-three of the forty sibling pairs tested were found to have similar alleles in the distal region of Xq28, which was significantly higher than the expected rates of 50% for fraternal brothers. A later analysis by Hu et al. revealed that 67% of gay brothers in a new saturated sample shared a marker on the X chromosome at Xq28. Sanders et al. (1998) replicated the study, finding 66% Xq28 marker sharing in 54 pairs of gay brothers. These studies only examined homosexuality in males.

However, two later studies (Bailey et al., 1999; McKnight and Malcolm, 2000) failed to find a preponderance of gay relatives in the maternal line of homosexual men. A study by Rice et al. in 1999 failed to replicate the Xq28 linkage. More recently, Mustanski (2005) failed to find the Xq28 marker in a complete genome scan of gay men’s DNA. Mustanski did however find autosomal markers at 7q36, 8p12 and 10q26.

The evidence for the Xq28 marker is therefore preliminary and has yet to be fully proved or disproved. Even at face value, the discovery of the Xq28 region would only show one genetic correlate of male homosexuality. Hamer's study was important though, as it was the first experiment to claim such a correlation. These findings do not suggest that the Xq28 region is necessary for homosexuality or singularly causes homosexuality, but rather that it might play one of many factors in causing homosexuality in some males.

A recent study supports X-linkage from a different perspective. Women have two X chromosomes, one of which is "switched off". In some cases though, it appears that this switching off can occur in a non-random fashion. Bocklandt et al (2006) reported that the number of women with extreme skewing of X chromosome inactivation is significantly higher in mothers of homosexual men than in age-matched controls without gay sons. 4% of controls showed extreme skewing compared to 13% of the mothers with gays sons and 23% of mothers with two or more gay sons.

Also, male homosexuality appears likely to be influenced by a complex genetic interaction which may be mediated by H-Y antigens in the mother’s immune system (see below). Whichever genes are implicated they almost certainly cause male brains to differentiate in a female typical direction.

As for female homosexuality, there remains little evidence from replicated genetic linkage studies.

Maternal linkage, birth order, and female fertility

Blanchard and Klassen (1997) reported that each older brother increases the odds of being gay by 33%. This is now "one of the most reliable epidemiological variables ever identified in the study of sexual orientation." To explain this finding, it has been proposed that male foetuses provoke a maternal immune reaction that becomes stronger with each successive male foetus. Male foetuses produce HY antigens which are "almost certainly involved in the sexual differentiation of vertebrates." It is this antigen which maternal H-Y antibodies are proposed to both react to and 'remember'. Successive male foetuses are then attacked by H-Y antibodies which somehow decrease the ability of H-Y antigens to perform their usual function in brain masculinisation.

Bocklandt, Horvath, Vilain and Hamer (2006) reported that some mothers of gay babies have extreme skewing of X chromosome inactivation. Using a sample of 97 mothers of homosexual men and 103 mothers of heterosexual men, the pattern of X inactivation was ascertained from blood assays. 4% of the mothers of straight men showed extreme skewing compared to 13% of the mothers of gay men. Mothers of two or more gay babies had extreme skewing of X inactivation of 23%. This extreme skewing may influence male sexual orientation through the fraternal birth order effect.

An alternate theory was proposed by Italian researchers in 2004 supported by a study of about 4,600 people who were the relatives of 98 homosexual and 100 heterosexual men. Female relatives of the homosexual men tended to have more offspring than those of the heterosexual men. Female relatives of the homosexual men on their mother's side tended to have more offspring than those on the father's side. The researchers concluded that there was genetic material being passed down on the X chromosome which both promotes fertility in the mother and homosexuality in her male offspring. The connections discovered, however, would explain only 20% of the cases studied, indicating that this might not be the sole genetic factor determining sexual orientation.

Homosexuals of either sex are more likely than the general population to be non-right handed (see Handedness and sexual orientation)

Pheromones correlation

Recent research conducted in Sweden has suggested that gay and straight men respond differently to two odors that are believed to be involved in sexual arousal. The research showed that when both heterosexual women (lesbians were included in the study, but the results regarding them were "somewhat confused") and gay men are exposed to a testosterone derivative found in men's sweat, a region in the hypothalamus is activated. Heterosexual men, on the other hand, have a similar response to an estrogen-like compound found in women's urine. The study was taken as evidence in support of the theory that certain chemicals act as pheromones in humans. The conclusion, that sexual attraction, whether same-sex or opposite-sex oriented, operates similarly on a biological level, does not mean that there is necessarily a biological cause for homosexuality. Researchers have suggested that this possibility could be further explored by studying young subjects to see if similar responses in the hypothalamus are found and then correlating this data with adult sexual orientation.

Early fixation hypothesis

Main article: Prenatal hormones and sexual orientation

The early fixation hypothesis includes research into prenatal development and the environmental factors that control masculinization of the brain. Studies have concluded that there is empirical evidence to support this hypothesis, including the observed differences in brain structure and cognitive processing between homosexual and heterosexual men. One explanation for these differences is the idea that differential exposure to hormone levels in the womb during fetal development may block masculinization of the brain in homosexual men. The concentrations of these chemicals is thought to be influenced by fetal and maternal immune systems, maternal consumption of certain drugs, maternal stress, and direct injection. This hypothesis is also connected to the fraternal birth order research.

Pathogenic theory

Main article: Pathogenic theory of homosexuality

Based on the relatively low frequency of homosexuality in the population, and the assumption that it is evolutionarily very disadvantageous, some have proposed that the cause may be a bacterium or virus.

Imprinting/critical period

This type of theory holds that the formation of gender identity occurs in the first few years of life after birth. It argues that individuals can be predisposed to homosexual orientation by biological factors but are triggered in some cases by upbringing. Part of adopting a gender identity involves establishing the gender(s) of sexual attraction. This process is analogous to the "imprinting" process observed in animals. A baby duckling may be genetically programmed to "imprint" on a mother, but what entity it actually imprints upon depends on what objects it sees immediately after hatching. Most importantly, once this process has occurred, it cannot be reversed, any more than the duckling can hatch twice.

A sort of reverse sexual imprinting has been observed in heterosexual humans; see the section on the "Westermarck effect" in Behavioral imprinting.

Several different triggers for imprinting upon a particular sexual orientation have been proposed.

A common hypothesis, especially among non-scientists, is that something about what young children see in the gender-roles behavior of adults, or some differences (possibly unconscious) in the way adults treat young children, somehow influence or determine a child's eventual sexual orientation.

This hypothesis, however, has not been supported by research findings that children of homosexuals are just as likely to be heterosexual as the general population and in reverse for children of heterosexuals in prevalence of homosexuality.

Exotic becomes erotic

Daryl Bem, a social psychologist at Cornell University, has theorized that the influence of biological factors on sexual orientation may be mediated by experiences in childhood. A child's temperament predisposes the child to prefer certain activities over others. Because of their temperament, which is influenced by biological variables such as genetic factors, some children will be attracted to activities that are commonly enjoyed by other children of the same gender. Others will prefer activities that are typical of the other gender. This will make a gender-conforming child feel different from opposite-gender children, while gender-nonconforming children will feel different from children of their own gender. According to Bem, this feeling of difference will evoke physiological arousal when the child is near members of the gender which it considers as being 'different'. Bem theorizes that this physiological arousal will later be transformed into sexual arousal: children will become sexually attracted to the gender which they see as different ("exotic"). This theory is known as Exotic Becomes Erotic (EBE) theory.

The theory is based in part on the frequent finding that a majority of gay men and lesbians report being gender-nonconforming during their childhood years. A meta-analysis of 48 studies showed childhood gender nonconformity to be the strongest predictor of a homosexual orientation for both men and women. For example, in a study by the Kinsey Institute of approximately 1000 gay men and lesbians (and a control group of 500 heterosexual men and women), 63% of both gay men and lesbians reported that they were gender nonconforming in childhood (i.e., did not like activities typical of their sex), compared with only 10-15% of heterosexual men and women. There are also six "prospective" studies--that is longitudinal studies that begin with gender-nonconforming boys at about age 7 and follow them up into adolescence and adulthood. These also show that a majority (63%) of the gender nonconforming boys become gay or bisexual as adults. There are no prospective studies of gender nonconforming girls.

Politics

The issue of genetic or other physiological determinants as the basis of sexual orientation is a highly politicised issue. The Advocate, a U.S. gay and lesbian newsmagazine, reported in 1996 that 61% of its readers believed that "it would mostly help gay and lesbian rights if homosexuality were found to be biologically determined". A cross-national study in the United States, the Philippines, and Sweden found that those who believed that "homosexuals are born that way" held significantly more positive attitudes toward homosexuality than those who believed that "homosexuals choose to be that way" and/or "learn to be that way".

See also

• Xq28
• Sexual orientation
• Innate bisexuality
• Norms of reaction
• Against Nature?
• Arnold Aletrino
• Sexual orientation and medicine

Additional resources

• BBC (April 23, 1999). Doubt cast on 'gay gene'. BBC News.
• Articles by Dr. Daryl Bem will be found at [1], including several on his EBE theory
• William Byne (May 1994). The Biological Evidence Challenged. Scientific American, vol. 270, pp. 50-55.
• Simon LeVay (updated at intervals) The Biology of Sexual Orientation, a literature review web page.
• Trisha Macnair (undated). Genetics and human behaviour. BBC Health.
• Timothy F. Murphy (Fall 2000). Now What? The Latest Theory of Homosexuality. APA Newsletter on Philosophy and Lesbian, Gay, Bisexual and Transgender Issues.
• Muscarella, F., Fink, B., Grammer, K., & Kirk-Smith, M. (2001). Homosexual Orientation in Males: Evolutionary and Ethological Aspects. Neuroendocrinology Letters, 22(6), 393-400. Full text
• Nuffield Council on Bioethics (2002). Genetics and human behaviour. London: Author. Chapter 10 discusses sexual orientation.
• Rahman Q. (2005). The neurodevelopment of human sexual orientation. Neuroscience and Biobehavioral Reviews 29 :1057–1066.
• Rines, J.P. & vom Saal, F.S. (1984). Fetal effects on sexual behavior and aggression in young and old female mice treated with estrogen and testosterone. Horm. Behav. 18:117-­12.
• Rosemary C. Veniegas & Terri D. Conley (2000). Biological Research on Women's Sexual Orientations: Evaluating the Scientific Evidence. Journal of Social Issues, vol. 56, pp. 267-282.
• Ryan, B.C. & Vandenbergh, J.G. (2002) Intrauterine position effects. Neurosci. Biobehav. Rev. 26:665--678.
• Simon LeVay & Dean H. Hamer (May 1994). Evidence for a Biological Influence in Male Homosexuality. Scientific American, vol. 270, pp. 44-49.
• T. J. Taylor (1992). Twin Studies of Homosexuality. Part II Experimental Psychology Dissertation (unpublished), University of Cambridge, UK.
• vom Saal, F.S. (1989) Sexual differentiation in litter bearing animals: influence of sex of adjacent fetuses in utero. J. Anim. Sci. 67:1824-1840.
• Vom Saal, F.S. & Bronson, F. (1980). Sexual characteristics of adult female mice are correlated with their blood testosterone levels during prenatal development. Science 208:597-599.