Signal + Noise

Mating Response

Do you find that when you think about an idea seriously for the first time, you suddenly notice references to it everywhere? Do you find yourself occasionally pondering a basic question that you should have asked before but somehow never did? There are few better reminders of how selective our attention can be or how much we tend to assume away.

It's been that kind of week for me. Three oddly connected events got me thinking about the mechanisms by which we recognize a potential mate.

Monday: Drosophila. I attended a fascinating lecture on alternative splicing of genes. After a gene is transcribed to an RNA sequence, parts of the sequence may be cut out and the remains spliced together to produce a messenger RNA sequence that will be translated into protein. It turns out that many genes' sequences can be spliced in multiple ways to produce different proteins. For example, one gene in humans can encode more than 38,000 protein varieties. These proteins guide neural connection during development, and each alternative splicing produces a variant that is needed at a particular time. This is a powerful mechanism for genetic regulation. It also gives a partial answer to the question of why the roughly 30,000 genes in humans are enough to produce such complexity: those 30,000 genes produce many more proteins.

The lecturer offered as an example the sex determination mechanism in the fly Drosophila melanogaster. Alternative splicings let some genes act as switches, and a hierarchical cascade of these switch genes appears to control all aspects of sexual differentiation including physical features, nervous system development, dosage compensation (adjusting the activity of X-chromosome genes to be equal in males and females), and I found out later, courting behavior. At the top of the hierarchy is the “Sex lethal” gene whose switch between alternative splicings is sensitive to the number of X chromosomes. Mutations in various genes in this hierarchy can produce interesting varieties such as females that are functionally male and intersex flies with features of both sexes.

As I listened to all this, I found myself wondering offhandedly if homosexuality could be explained by a switch gene that governed the recognition of one sex as an appropriate target for attraction and courtship. I realized then that I had no idea how we do recognize one sex as potential mates. Without having thought about it carefully before, I had assumed vaguely that a neural representation of the opposite sex, when triggered, provoked a hormonal mating response that affects and is in turn affected by higher-level neural processing (e.g., thinking about sex can produce arousal). It seemed reasonable that this would involve a genetic component guiding endocrine and neural development and social experience to “train” our idea of what's attractive. But the Drosophila example showed me how complex and interesting the genetic and neural details could be.

Tuesday: Bare Midriffs. TK's testosterone surge begins. That's what TW and I call it, at least, but we don't really know how to explain his strange behaviors. His TV that day consists of playing the same animated song on DVD over and over while — here's the strange part — using the zoom feature to crop close on the cartoon singer's bare midriff and tiny t-shirt. Later in the week, TK chooses to watch the only scene from the Sound of Music in which Maria is less than fully dressed. Hmm. Second, he keeps trying to rub TW's stomach and asks her frequently to pick him up. Third, he focuses excessive attention on nearby girls or women. When I watch him the next day on the pre-school playground, he's following the girls around like a puppy. This is six-sigma behavior, but otherwise, he's acting normally. What's going on here? Do four-year-old boys have cyclical testosterone surges? Things settle back to normal by Saturday, but I'm puzzled all week.

Friday: Testosterone (for sure this time). Via OxBlog, I see this report of a study demonstrating that male testosterone levels rise after chatting with a female. Those with the biggest changes tried hardest to impress her and reported finding her more attractive. The study raises many interesting questions. What came first, the testosterone or the attraction and flirting behavior? (Could married men exhibit lower testosterone levels because they don't flirt as often??) How does the observed change in testosterone levels compare with that produced by a confrontational encounter with another male or by imagined sexual activity? Would the result still hold if the chat were held without physical proximity, say by video or even by phone, or with proximity but no line of site (not sure how to do that study)? That night I dreamed that TK wrestled a giant Drosophila fly over the chance to rub a winsome lab assistant's bare stomach.

So on Saturday, with my curiosity piqued, I tried to get a picture (rough and fuzzy though it may be) about the current understanding of sex determination and gender recognition. I focused first on Drosophila both because so much is known about it and because I had an entry-point from Monday's lecture.

The first step was to learn more about the fly's sexual differentiation mechanism because I had only been told about bits and pieces. My main question was what parts of the cascade of switch genes (if any) might be responsible for mating drive and behavior. Backtracking from the references of more technical papers, I found this review that compares sex determination mechanisms in two important “model organisms”, the fly Drosophila melanogaster and the worm (nematode) Caenorhabditis elegans. It's nicely written and very accessible to non-experts (like me). The contrast between worm and fly exemplifies the large cross-species variation in the sex-determination mechanism, and it put the different switches into some perspective. This review hinted about potential behavioral connections, but at that point (it seems) the behavioral side had not been tracked down. I also found a more recent (and more technical) review on Drosophila that lays out the system and has some nice pictures, but it focuses mainly on sexual dimorphism. [Not being an expert in genetics, I often find this genetics web glossary very helpful in reading these papers.] My most relevant finding was that a particular gene in the hierarchy of switch genes, fruitless (go figure), is believed to control all aspects of Drosophila's courtship and mating behavior.

For example, there are bisexual flies. Mutations in the fruitless gene can lead to male flies that indiscriminately target males and females for courtship and mating. This paper describes the mechanism in detail; the introduction and discussion are useful and accessible. Here's the money quote:

In considering more generally the question of what role genes play in determining sexual orientation, one must first recognize that species differ widely in the relative contributions of genes and environment to male sexual behavior. Male courtship behavior (and, by implication from our results, also sexual orientation), in flies is a fixed action pattern , i.e., is largely genetically programmed, although courtship behavior in flies can be modified to a limited degree by experience (reviewed by Hall, 1994; Greenspan, 1995). At perhaps the other extreme, human male courtship behavior seems to be highly modifiable by experience (our unpublished data). Nevertheless, there is a variety of evidence in vertebrates, including humans, suggesting that male sexual behavior, including sexual orientation, has a genetic component (reviewed by Breedlove, 1994; LeVay, 1996). First, we note evidence that a sexually dimorphic portion of the human brain (known in mammals to be involved in courtship and mating behavior) is also dimorphic in homo- versus heterosexual males (reviewed by LeVay, 1996). Second, prenatal exposure to sex steroid hormones affects the types of sexual behaviors displayed by mature mammals, and hormone and receptor levels are under genetic control. Third, the choice of male targets by homosexual rams appears to have a heritable component that involves a steroid hormone axis (Perkins et al., 1995). Fourth, the possibility that sexual orientation could have a genetic etiology in humans is also suggested by results from twin studies on male homosexuals (reviewed by LeVay, 1996) and by a mapping experiment involving familial occurrences of homosexuality in males (reviewed by LeVay, 1996; see also Hu et al., 1995b).

The LeVay (1996) reference is to this book, which appears (I haven't read it) to be a well-reputed scientific overview of sexual orientation.

The Ryner review above gives prominent mention to the role of experience. But this interesting and accessible essay in Cell argues for care in what is ascribed to genes and “experience:”

Do genes control behaviors? This long-standing question at the center of the nature/nurture debate is usually answered by neurobiologists, ethologists, and geneticists by saying: “Well, sort of, but both genes and environment are important in shaping behaviors.” Here we argue, from our perspective as geneticists and biologists, that such answers are flawed in three ways: (1) A significant number of behaviors (e.g., certain fixed action patterns and species-specific innate behaviors) are relattively unaffected by environment and thus appear likely to be largely dictated (in some manner) by genes; (2) They fail to distinguish between different levels at which genes might control behavior; and (3) By placing an emphasis on the genetic and environmental components of the differences between individuals in the expression of behavior, such answers may have obfuscated understanding how the basic potentials for particular behaviors are established.

The authors use the fruitless (fru) gene as an example in discussing the role of genes in regulating complex behaviors.

An anthropomorphic description of fly courtship behavior can be made that is very similar to the basics of courtship in humans and many other species: recognize a potential mate (distinguish your species, and its sex, from others); get their attention (tapping?); if they don t run away, and perhaps show some interest, court them (beguile them with a love song?); try to arouse them (licking?); and finally, attempt copulation. Such a basic sequence would seem to be one reasonable strategy for reproductive success. Given the diversity of human sexual behaviors that exists, if there is a human counterpart to fru, such a gene's role might just be to see that the neural circuits were built that coordinate and order such basic steps. The actual events that comprise each step in such a sequence could be shaped by individual-to-individual variations in experience and genotype. This is not dissimilar to what appears to be the basic pattern for a number of behaviors in higher organisms. For example, there is a basic circuitry for song production in certain songbirds. In some cases even the rudiments of song appear to be innate, but many aspects of a bird s song in these species are learned (for review: Bottjer 1997; Alcock, 1998). Generalizing this idea, we also note that many human behaviors are clearly modified by experience. Thus, if the potentials for various biologically meaningful human behaviors are built into the nervous system by genes like fru, it is likely that this is done by using such genes to build the basics of the circuit subserving a behavior, as well as building in the potential for experience to shape and mold that circuitry.

They make a provocative argument that is worth pondering.

Berkeley psychologist Marc Breedlove, on the other hand, argues that experience can physically alter the nervous system even in adulthood and that it has a bigger role than previously thought in gender differences. Two news releases describing his work can be found here and here. He shows that sexual activity and the concentration of circulating hormones (e.g., androgen) can alter the size of brain regions in rats on the order of weeks. Here is an abstract to his review on the subject, but the paper is not available on line.

In the end, I haven't answered my original question of how we recognize another organism as a potential mate, which isn't surprising given the huge relevant literature. Drosophila turns out to be a poor model for sexual differentiation in humans or other mammals, where hormones play a critical role. (Nonetheless, when one of the switch genes (transformer2) in the fly is replaced with a human homologue, no significant changes are observed. No one yet knows what this means.) For me, one of the most interesting aspects of this question is the necessary interaction between brain and gene. Flies have a more-or-less fixed action pattern for mating behavior, but I haven't seen any definitive studies (they may exist, of course) that describes the sensory stimuli and neural processes that activate that response. For humans, is the stimulus-to-behavior link more flexible? I don't know offhand of any brain imaging studies on primarily the recognition of the opposite sex. Neuroscientists have found a focused brain area (in the fusiform gyrus) for face recognition as well as sub-areas that respond differentially to faces based on race (same/different). Recognizing faces of the other gender must be even more important evolutionarily, so I'd be surprised if a similar functional area weren't found. (There may have been such studies done, but I don't recall any at the moment.) But more than face recognition is involved. What comprises a male's concept of a female (or vice versa) at the neural level? How much can it be altered by experience or values? What are the biological constraints on what we find attractive?

As always, questions lead to more questions. My search for answers was unsuccessful, but hardly fruitless.

Posted by Chris at 11:44 PM on 9 November 2003 | TrackBack