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giles337 wrote:I think the point being made CE, with regards to your last comment, is that Homosexuality is a feature of the Human race, and will always be there, unless the human race is wiped out.

Just my two penn'th, but surely if there was a "gay gene" which, IMO is highly doubtful; surely it would be exceeddingly difficult to be passed on through generations?

boo's daddy wrote:I would go further and say that scientific studies of it are so primitive that we are much better using the evidence of our experience.

Many GLB people I know are ambivalent about this because, if "gayness" is identified as a biologically determined phenomenon, isn't there a danger that it detracts from the "equality" argument?

In the one hand, a biological basis feeds the "disease" argument; on the other, what if we find that it IS a choice?

Wouldn't it be better to sort the politics out separately and argue strongly that this is a matter of equality and not cause?

Regarding the research you cite, we should not be surprised at all that, for example, the patterns we see on some machine looking at gay men's brains show similarities to the patterns on straight womens' brains when they smell men. After all, they both fancy men!

This is news to me; any chance of a link/references?

C Elegans wrote:Sorry, I missed this previously. Hello and welcome to the forums!

How is it better to use anecdotal evidence (ie personal experience) that is subject to selection bias, confirmation bias, individual subjective interpretation, etc that to use scientific studies as a means to gain understanding and knowledge about something we don't know?

Lateral dominance, ie whether you are right- or left handed/footed/eyed is biologially determined (both genetically and prenatally),

Of course it would, I was just pointing out that research about sexual orientation can be useful also for social issues, since Fiona opposed this.

EDIT: I found some, but not full references, ie not the journal they were published in and the title, but you should be able to find them anyway: Pillard & Weinrich 1986, Pillard 1990, Bailey & Bell 1993, Bailey & Benishaw 1993, Pattatucci & Hamer 1995. All are published in the peer reviewed scientific press.

Fiona wrote:If you are saying there is no such thing as scientific research aimed at finding the gay gene, I still cannot agree. For example:

http://www.gnxp.com/MT2/archives/004047.html

fruitless Splicing Specifies Male Courtship Behavior in Drosophila
Ebru Demir and Barry J. D1ckson

Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr-Gasse 3–5, A-1030 Vienna, Austria

Introduction

Animals are born not only with their characteristic body plan and morphology, but also a set of innate behaviors, or instincts, that are manifested as stereotyped responses to environmental stimuli (Tinbergen, 1951). Enormous progress has been made over the past several decades in elucidating the developmental processes that direct the formation of the body plan and its parts. In contrast, our understanding of how innate behaviors are specified is still rudimentary at best. It is not even clear whether the general principles gleaned from the study of morphological development also apply to the development of behavior. For example, body parts are often specified by “switch” or “selector” genes, the action of which is both necessary and sufficient to trigger the development of a complete anatomical structure (Garcia-Bellido, 1975). Might instincts be specified in a similar way? Are there behavioral switch genes that create the potential for a complex innate behavior (Baker et al., 2001)? Or, at the other extreme, do instincts emerge diffusely from the combined actions of the vast number of genes that contribute to nervous system development and function, so that no single gene can be said to specify any particular behavior (Greenspan, 1995)?

If behavioral switch genes exist, then one place in which they are likely to be found is in the specification of sexual behaviors (Baker et al., 2001). Males and females generally have dramatically distinct and innate sexual behaviors. These behaviors are essential for their reproductive success, and so strong selective pressure is likely to have favored the evolution of genes that “hardwire” them into the brain. The initial steps of sexual differentiation have been well characterized for several model organisms, and genetic perturbations in these sex-determination hierarchies can alter all aspects of the sexual phenotype—innate behaviors as well as gross anatomy. Several genes near the top of these sex-determination hierarchies thus qualify as developmental switch genes, but they cannot be considered specifically as behavioral switch genes. A switch gene for a sexual behavior should act to specify either male or female behavior, irrespective of the overall sexual phenotype of the animal. A candidate for such a gene is the fruitless (fru) gene of Drosophila, which is intimately linked to male sexual orientation and behavior (Baker et al., 2001).

Male courtship in Drosophila is an elaborate ritual that involves multiple sensory inputs and complex motor outputs (Hall, 1994; see Movie S1 in the Supplemental Data available with this article online). It is largely a fixed-action pattern, in which the male orients toward and follows the female, taps her with his forelegs, sings a species-specific courtship song by extending and vibrating one wing, licks her genitalia, and finally curls his abdomen for copulation. If the female is sufficiently aroused and has not recently mated, she accepts his advances by slowing down and opening her vaginal plates to allow copulation. An obvious but nonetheless remarkable aspect of this behavior is that mature males court only females, never other males, whereas females do not court at all.

Certain loss-of-function alleles of the fru gene disrupt both male courtship behavior and sexual orientation: performance of the courtship ritual is below par, and it is directed indiscriminately at either sex (Anand et al., 2001, Ito et al., 1996, Lee et al., 2001, Ryner et al., 1996 and Villella et al., 1997). Strong fru alleles completely block courtship behavior, but weaker fru alleles variously disrupt individual steps, with each step affected in some allelic combination (Anand et al., 2001 and Lee et al., 2001). This suggests that fru is required for every step of the courtship ritual, not just for a single critical step. For all of these fru alleles, female morphology and behavior appear normal.

Of the many genes known to be involved in male courtship behavior (Billeter et al., 2002), fru is unique in that it is sex-specifically spliced (Ito et al., 1996 and Ryner et al., 1996). Alternative splicing at both the 5′ and 3′ ends of the fru locus generates a complex set of transcripts, all of which encode BTB domain-containing zinc finger proteins. Most of these transcripts are not sex specific, but those initiated from the most distal (P1) promoter are spliced differently in males and females. The alleles of fru that affect male courtship are all associated with chromosomal insertions, deletions, or rearrangements that specifically disrupt these sex-specific P1 transcripts (Anand et al., 2001 and Goodwin et al., 2000). This has led to the hypothesis that the male-specific splicing of the fru P1 transcripts specifies male courtship behavior and sexual orientation (Baker et al., 2001). This is the hypothesis we test here.

We used gene targeting by homologous recombination to generate alleles of fru that are constitutively spliced in either the male or female mode. Forcing female splicing in the male results in a loss of male courtship behavior and orientation, confirming that male-specific splicing of fru is indeed essential for male behavior. More dramatically, females in which fru is spliced in the male mode behave as if they were males: they court other females. Thus, male-specific splicing of fru is both necessary and sufficient to specify male courtship behavior and sexual orientation. A complex innate behavior is thus specified by the action of a single gene, demonstrating that behavioral switch genes do indeed exist and identifying fru as one such gene.

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Discussion

Development endows an animal with the morphology and instinctive behaviors characteristic for its species, preparing it for survival and reproduction in the environment into which it is likely to be born. An animal’s instinctive behaviors are just as stereotyped and just as characteristic for its species as its morphology, and so one might expect to find a similar logic underlying the genetic programs that specify morphology and behavior. Yet, whereas morphological development has now largely succumbed to the attack of classical forward genetics in a few model organisms, the same approach has made only modest inroads into the developmental origins of complex innate behaviors. Does this reflect a fundamental difference in the ways behavior and morphology are specified during development or just a lack of attention to the problem of behavioral development?

One of the lessons from the genetic analysis of morphological development is that anatomical features are often specified by switch genes, the action of which is both necessary and sufficient to direct the formation of a particular feature. A striking example of such a morphological switch gene is the eyeless gene of Drosophila, which is both necessary and sufficient for eye development (Halder et al., 1995). If analogous genetic principles guide the emergence of both morphology and behavior, then we should also expect that at least some innate behaviors are specified by switch genes. The action of such a behavioral switch gene would be both necessary and sufficient to hardwire the potential for the behavior into the nervous system. Until now, such behavioral switch genes have been elusive. Here, we have demonstrated that the fruitless (fru) gene of Drosophila is a switch gene for a complex innate behavior: the elaborate ritual of male courtship.

fru as a Switch Gene for Male Courtship Behavior

fru has long been known to be required for male courtship behavior (Gill, 1963). In this regard, however, fru is not particularly unusual. Many other genes have also been implicated in male courtship behavior, and in one way or another, a substantial fraction of the genome is likely to be required for a male to be capable of and inclined to court a female. fru only assumed its more prominent position when it was molecularly characterized, revealing that some of its transcripts are spliced differently in males and females (Ito et al., 1996 and Ryner et al., 1996). This led to the hypothesis that splicing of fru specifies male courtship behavior (Ito et al., 1996 and Ryner et al., 1996). Although widely discussed (e.g., Baker et al., 2001), this hypothesis has remained untested for almost a decade. We have now confirmed the key predictions of this hypothesis by showing that male splicing is indeed necessary for male courtship behavior (Figure 2) and is also sufficient to generate male behavior by an otherwise normal female (Figure 4).
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The distinct roles of fru and dsx in sexual development are clearly illustrated by the differences between animals that produce either only FruM or only DsxM. Animals that express DsxM but not FruM (either fruF males or dsxM females) resemble normal males but do not court (Figure 2A; Taylor et al., 1994). Conversely, animals that express FruM but not DsxM (either fruM females or dsx males) do court, even though they resemble normal females (Figure 4A; Villella and Hall, 1996). Thus, FruM is both necessary and sufficient for male courtship, whereas DsxM is neither necessary nor sufficient. The role of DsxM in courtship may simply be to provide the gross male anatomy needed for its optimal execution. This anatomical contribution of DsxM includes the formation of male reproductive organs and external genitalia (Burtis and Baker, 1989), the generation of the neurons that innervate these organs (Taylor and Truman, 1992), and the formation of male-specific taste sensilla on the forelegs that may house pheromone-detecting neurons (Bray and Amrein, 2003).

An open question is whether fru specifies male-like behavioral patterns more generally or is exclusively involved in male courtship behavior. We have focused our study on courtship behavior because this is the most dramatic, most robust, and best understood of the sexually dimorphic behaviors in Drosophila. But other behavioral patterns, such as aggression (Chen et al., 2002 and Nilsen et al., 2004), are also sexually dimorphic, and it will be interesting to determine to what extent these behaviors depend on fru.
How Does fru Specify Male Courtship Behavior?

A behavioral switch gene such as fru must act through the relevant neural circuits. In the accompanying paper (Stockinger et al., 2005 [this issue of Cell]), we begin the anatomical and functional characterization of the neurons in which FruM is expressed and present evidence that they form a neural circuit that is largely dedicated to male courtship behavior. As the same circuit seems to be present in the female, we reason that FruM most likely exerts its effect by modulating the function rather than the assembly of this circuit. Nevertheless, the critical period for FruM to do so is evidently during development, as adult males begin courting soon after eclosure, without any prior exposure to another fly. Moreover, experiments involving conditional expression of tra have suggested that male behavior is irreversibly programmed during the early- to midpupal stages (Arthur et al., 1998), coincident with the onset of FruM expression in increasing numbers of neurons in the male nervous system (Lee et al., 2000).
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The fru target genes themselves are unknown, as are, for the most part, their effects. The few cellular functions so far ascribed to fru are the regulation of the number or size of synaptic terminals in specific glomeruli of the antennal lobe (Stockinger et al., 2005) and at the MoL (Billeter and Goodwin, 2004), as well as the production of serotonin in certain male-specific neurons of the abdominal ganglion (Lee and Hall, 2001). A fascinating question for the future is whether profound differences in sexual behavior arise as the sum of many subtle differences such as these, or are instead primarily due to a still unknown action of FruM in a few key “decision” neurons.
Single Genes and Complex Behaviors

Complex behaviors require the actions of vast numbers of genes, and so it is quite easy to isolate mutations in single genes that disrupt a particular behavior. Almost all of these mutations are relatively uninformative as to the genetic basis of that behavior or indeed the relationship between genes and behavior more generally. More useful are genes for which different allelic states result in different manifestations of the behavior. Several fascinating examples of such genes have been found, and all have provided important insights into the behaviors they influence. This includes, for example, the npr-1 neuropeptide receptor gene in the control of social feeding in C. elegans (de Bono and Bargmann, 1998), the foraging cGMP-dependent protein kinase gene in Drosophila social feeding behavior (Osborne et al., 1997), the vasopressin 1a receptor gene in affiliative behavior in voles (Lim et al., 2004 and Young et al., 1999), and, more controversially, the serotonin transporter gene in human depression (Ogilvie et al., 1996). Importantly, fru differs from “behavior genes” such as these in one critical aspect: it does not influence a behavior as it happens, but rather acts during development to create the potential for a behavior (Baker et al., 2001).

Might there be other behavioral switch genes like fru, and if so, how will we find them? The lack of obvious candidates is no reason to doubt that other behavioral switch genes exist. Indeed, in many ways it is almost fortuitous that this function of fru has been discovered at all. Mutations that eliminate all fru function are lethal and hence uninformative as regards to fru’s role in male courtship. This role only came to light through the isolation of relatively rare alleles that disrupt specific transcripts (Gill, 1963). Even then, it was not until its molecular cloning that fru acquired any particular significance (Ito et al., 1996 and Ryner et al., 1996) and only now, through precise gene manipulations, that its role as a switch gene has been established. Classical forward genetics might not be the most effective way to search for behavioral switch genes, particularly if, like fru, the genes also have essential but unrelated functions during development.

Perhaps even more challenging will be recognizing a behavioral switch gene when we find one. Formally, this requires a sufficiency experiment, which involves asking if ectopic expression can specify a novel behavioral pattern in an otherwise normal animal. It is difficult to envision how such an experiment might be performed for anything other than a sexually dimorphic behavior. Hence, if we are to identify switch genes for behaviors that are not sex specific, then we must relax this strict criterion. What other features of fru could serve as a guide in assessing other candidate switch genes? Four aspects of fru stand out. First, as already noted, it acts during development to create the potential for the behavior, rather than directly influencing the behavior itself. Second, it appears to be involved in most or all aspects of the behavior, not just a single component. Third, loss-of-function mutations do not result in a general impairment of neural function, but a specific behavioral deficit. Fourth, it is required in a diverse set of neurons with little in common except their role in this behavior, to which they may also be dedicated. Candidate vertebrate genes that fulfill at least some of these criteria have been linked to behaviors at opposite extremes of complexity: the ETS transcription factor genes Er81 and Pea3 in the spinal stretch reflex (Lin et al., 1998) and, more speculatively, the forkhead-domain transcription factor gene FoxP2 in human language ability (Vargha-Khadem et al., 2005).

Finally, the concept that a switch gene can specify an entire innate behavior in no way denies the critical role of complex gene networks, just as the concept of a morphogenetic switch does not deny the existence of complex regulatory networks among the genes it regulates. These networks add both detail and robustness to the behavioral or morphological pattern initially laid down by the switch gene at the top of the hierarchy. The notion of a behavioral switch gene does, however, imply that at least some instinctive behaviors develop according to the familiar genetic logic of morphological development. Given the appropriate genetic tools, behavioral instincts should ultimately succumb to the same kind of molecular genetic analysis that has so successfully revealed the principles of morphological development.

Fiona wrote:It is true that much of this is reported in the press and it will perhaps distort what is being done. Nevertheless it seems to me that research is being done on this topic. Maybe this isn't a scientifically respectable journal but on google search there are many such reports. Could it be that in the mainstream scientific press people are careful to describe what they are doing in different words ? just a thought

Chanak] From my understanding - and perhaps I understand things I have read differently? - it is believed that no wrote:
Your understanding is correct. The "one" gene hypothesis for complex behaviours, traits and even most diseases was left long ago simply because the findings were not consistent with this idea. Some diseases are caused by alternations of one gene, but these are very rare compared to diseases where no single gene alternations have been found. Instead, it is typically a long range of different genes that form a network, and different such networks, that disposes or protects against a certain disease. Genes interact a lot with each other, and with environmental factors, so it's not even the same pattern of genes that may increase the risk for developing schizophrenia with 10%.

It should be noted that so far, no gene has been identified that explains more than 1% of the variance in human behaviour. (The expression "explaning the variance" means that not one gene has been found that affect this certain behaviour more than 1%.) On the contrary, a gene explaning 1% of the variance in a human behaviour, is viewed as extremely influencial since the usual range of explained variance is 0.1-0.2%!

boo's daddy] I guess my reason for saying this is because people often use scientific evidence which addresses one question (e.g. are there similarities between gay men's and straight women's brains?) to answer another (is sexuality inherent or learned behaviour?) Crude examples I know. [/quote] I think one of the problems we scientists have when communicating with other people is that 1) popular media often works against us because they distort and bias the findings in order to make them suitable for tabloids and 2) scientific findings are mostly made by conducting 100's of studies and then summarise the results. And no layman wants to read 300 papers about hormonal cycles in rats wrote: But there's an issue, of course, in the selective interpretation of research (we need more systematic reviews!).

How do you mean selective interpretation? I have thought a lot about how to improve the peer review system but I can't really find a way to improve it without vastly prolonging the already slow review process. Do you have any suggestions? I think the double -blind system works well actually, except in very narrow areas.

Good old fashioned empathy is a jolly effective shortcut through a lot of this kind of bias, in my experience. I've seen lots of (esp older generation) homophobes "converted" by a conversation with a gay bloke in a way that would be very hard to bring about with hard evidence.

Fiona wrote:However what I think I was trying to say was that research into a genetic basis for sexual behaviour does go on and on my reading of the article that is exactly what they are doing.

I would not expect controversial language in a scientific paper and I do not find it here. I still wonder why this research is undertaken at all. I see that they chose to investigate sexual behaviour because that was a particularly fruitful line of research given what they already knew and what they were able to do. I also see that they talk about similar lines of research into other complex behaviours either in prospect or already done (I think).

Science is funded and some things are interesting to the fund-holders and some are not. This process arguably affects what is done. You said earlier that the number and cost of this kind of research is quite small in the scheme of things.

I am not arguing that scientists are entirely responsible for the use which is made of their research but the very fact that the link I found was to a "popular" site is telling. I, and many other people, have to rely on the press to get any idea of what is going on. I know it is misleading and I know it can be deliberately distorted. So do scientists. It is not good enough to retreat from the consequences.

For myself, particularly in the political climate, I think that the dangers may outweigh any benefit, though I am open to persuasion. I object to any use of public money to further this type of research; and I would like to know the motivations of the other big sources of money.

boo's daddy wrote:Google Scholar is an improvement. PubMed/Medline misses a lot of the (esp European) literature. You need to do EMBASE as well (though it costs an arm and a leg) plus whatever databases are specific to your area.

Editorial:
I think the problem is usability, or the lack of it.

Researchers publish research for other researchers, not for the public or even informed professionals such as clinicians.

There's good evidence that peer review, even when it's blinded, reinforces the biases of reviewers rather than ensuring quality. The answer, IMO, is to ditch journals and have fully open access publishing.

Authors should provide structured abstracts with particular attention to defining the research question clearly. Reviewers should use validated methodological criteria which would be embedded into the online publishing system. This would focus on:

1) does the research REALLY address a clearly defined question?
2) was the study design appropriate for this type of question?
3) were the methods used rigorous enough to rule out bias?
4) what are the results and are they important?

boo's daddy wrote:The other side to it is that of publication bias: "uninteresting" research is far less likely to be published.

I have a bunch of references in my refman database at work which I'll fish out when I get a chance. Offhand, the only one I can recall is this one from Bandolier:
http://www.jr2.ox.ac.uk/bandolier/band88/b88-4.html

boo's daddy wrote:I think you're assuming that impact factors are an objective measure of the importance of research. I don't know that that's the case.

It may be for researchers, who want their work to be cited by other researchers. I work with clinicians, who are concerned with validity, importance and applicability.

It's interesting that you say reproducibility is not necessarily a desirable factor in peer review. I can see your point, but I think it underlines my argument: if these sorts of study tell us anything, it's that peer review is a rather mysterious process which is subject to the biases of individual reviewers.

Anecdotally, I was involved in some training of BMJ reviewers a few years ago. It was part of a study to test out whether training (face-to-face or CD-ROM) improved the quality of their reviews. When we asked them what criteria they used to recommend papers for publication, validity was number 8 on the list.

I wouldn't like to lose the good things about peer review (whatever they are), I just think it doesn't work as it is in terms of quality assurance.