Genetics and evolution of sexual orientation

Human same-sex sexual behaviour (SSB) is heritable, confers no obvious direct reproductive or survival benefit and can divert mating effort from reproductive opportunities. This presents a Darwinian paradox: why has SSB been maintained despite apparent selection against it? Professor Verweij will present results from a study showing that genetic effects associated with SSB may, in individuals who only engage in opposite-sex sexual behaviour (OSB individuals), confer a mating advantage. A genome-wide association study on 477,522 individuals was performed, revealing five loci significantly associated with SSB. In aggregate, these genetic variants accounted for 8 to 25% of individual differences in SSB. Using the results from this study (the genome-wide effect estimates) and results from a genome-wide association study on number of opposite-sex sexual partners in 358,426 individuals, the authors show that, among OSB individuals, genetic effects associated with SSB are associated with having more opposite-sex sexual partners. Simulation analyses suggest that such a mating advantage for alleles associated with SSB could help explain how it has been evolutionarily maintained. Several important caveats will be discussed.

About 75% of genetically identical twins who are homosexual have heterosexual co-twins, and it is largely unknown what causes their difference. However, the majority of past work with such twin pairs was based on self-reports, which can be biased, and how these twins truly differ remained uncertain. The author will summarise research from our lab showing that these twins differ in behavioural, physiological, and anatomical traits linked to sexual orientation: gender-nonconformity, genital arousal, and finger length ratios, respectively. Dr Rieger will then propose a mechanism that explains their different development. About 30% of identical twins develop with separate placentas. Maternal androgens or antibodies could diffuse differently through these placentas, affecting the differentiated development of the twins. The author will also propose a study design to indirectly test this hypothesis.

Male homosexual orientation remains a Darwinian paradox, as there is no consensus on its evolutionary (ultimate) determinants. Much work in the previous decades has focused on kin selection, with the conclusion that this explanation alone seems insufficient and cannot explain the origin or the maintenance of same-sex sexual preference in our species. There are several other evolutionary explanations, such as the pleiotropic effects which are now scrutinized, although there is no consensus yet on the nature of the advantageous trait that would be selectively favoured and linked to same-sex attraction. One intriguing feature of homosexual men is their higher male birth rank compared to heterosexual men, best explained by a fraternal birth order effect, and not by a pleiotropic effect on female fertility. However, the effect of male birth order on sexual orientation requires an evolutionary explanation. An overall picture of possible evolutionary determinants of same-sex orientation will be presented. 

Twin studies and other analyses of inheritance of sexual orientation in humans has indicated that same-sex sexual behaviour has a genetic component. Previous searches for the specific genes involved have been underpowered and thus unable to detect genetic signals. Dr Ganna together with a group of scientists perform a genome-wide association study on 493,001 participants from the United States, the United Kingdom, and Sweden to study genes associated with sexual orientation (see the Perspective by Mills). They find multiple loci implicated in same-sex sexual behaviour indicating that, like other behavioural traits, nonheterosexual behaviour is polygenic.

While prenatal androgens largely mediate sexual behaviour and preferences in non-human animals, the evidence has been mixed when it comes to human sexual orientation and gender expression. In this talk, the authors will present data suggesting that there are multiple biological pathways underlying sexual orientation among humans, and early androgens exposure contributes to the sexual orientation and gender expression of a subset of gay men. The authors approach this research from a translational approach evaluating how the principles gained in studying sexual differentiation of the brain and behaviour in rodent models may apply to humans. As such, Dr Swift-Gallant will also present preliminary work from our rodent models suggesting that alternate mechanisms, such as the gut microbiota, contribute to socio-sexual behaviours and thus may be considered in understanding the biological underpinnings of same-sex sexual orientation in humans.

In Thai culture, same-sex attracted individuals are often considered to be gender-nonbinary and referred to as pheet thii saam, which translates as “third sex/gender.” Males who display androphilia (ie, sexual attraction to adult males) present as either relatively more masculine (ie, gay) or as transfeminine (ie, sao praphet song, which translates as “a second kind of woman”). Females who display gynephilia (ie, sexual attraction to adult females) present as relatively more feminine (ie, lesbian), transmasculine (ie, tom, which has a similar connotation as “tomboy”), or as feminine individuals who are romantically/sexually attracted towards toms (ie, dee). This presentation will detail three recent and ongoing evolutionary studies focusing on same-sex sexual orientation in which these groups of pheet thii saam individuals were compared with heterosexual men and women. Study 1 focused on the numbers of offspring produced by study participants and demonstrates lowered direct reproduction among pheet thii saam relative to their heterosexual counterparts. Study 2 tested the kin selection hypothesis, which posits that same-sex attracted individuals offset their lack of reproduction by allocating kin-directed altruism towards close kin, thus enhancing inclusive fitness. Study 3 tested the balancing selection hypothesis, which posits that the relatives of same-sex attracted individuals exhibit increased reproduction, which could offset same-sex attracted individuals’ lack of reproduction. Together, findings from these studies add to existing empirical work on the evolutionary maintenance of same-sex sexual attraction and help to delineate possible evolutionary differences based on the sex and gender expression of same-sex attracted individuals. 

For over 50 years, scientists across multiple disciplines (genetics, anthropology, endocrinology, psychology) have tried - but failed - to nail down the cause of human same-gender sexual expression. Although studies confirm that same-gender sexual behaviour is genetically influenced, the magnitude of this influence appears relatively small, accounting for only 8-25% of the population variance in same-gender sexual behaviour (Ganna et al, 2019). Further complicating matters is the fact that “same-gender sexual expression” does not appear to represent a single phenotype or genotype. Subtypes of same-gender sexuality (early developing, later developing, exclusive, bisexual, fluid, stable) have been documented by anthropologists and psychologists for decades, and recent genetic research suggests that these subtypes may correspond to distinct genetic profiles. Ganna’s (2019) study of the full genomes of over 450,000 individuals made the startling discovery that the genes associated with ever having pursued same-gender sexual behaviour were not the same as the genes associated with degrees of same-gender sexual behaviour. This finding directly contradicts the notion that same-gender and other-gender orientations represent two ends of a single genetic continuum, and suggests scientists may have failed to properly characterize the phenotype of sexual orientation. An additional weakness of prior genetic-evolutionary research on sexual orientation is the inattention to gene-environment interactions, particularly those involving childhood adversity. One of the most robustly documented environmental differences between individuals with same-gender sexual behaviour and individuals without such behaviour is exposure to childhood adversity, including financial hardship, neighbourhood violence, residential instability, physical/sexual abuse, and the unavailability of reliable adult care and protection. From an evolutionary perspective, there is arguably no category of environmental experience as influential on human genetic expression as childhood threat and nurturance. Decades of developmental research has shown that the children’s brains are exquisitely sensitive to such experiences, and decades of evolutionary research has explained why: Early life experiences of threat and nurturance are treated by the developing human brain as “hints” about the types of survival and reproductive challenges a child may face in the future. Accordingly, the fact that same-gender-attracted adults report twice as much childhood adversity as heterosexuals is simply too significant to ignore, especially for scientists grounded in evolutionary models of human development. We need genetically-informed understandings of sexual diversity that adequately capture the full range of human sexual phenotypes and the full range of gene-environment interactions that may shape sexual development. This broadened perspective may lead us to retire the notion of “sexual orientation” altogether, and to question our own culturally-grounded assumptions about sexual “traits.” Gould and Lewontin famously cautioned evolutionary biologists against over-interpreting salient patterns in natural phenomena, noting that some of these patterns are simply “spandrels,” defined as phenotypic by-products of other evolved traits and processes that we fail to observe. In light of this caution, we should actively investigate the possibility that same-gender sexual expression is an “accidental” form of human patterning, whose genetic underpinnings have little to do with either sexual differentiation or sexual reproduction.