A simple story gets complicated


People, scientists included, are always looking for simple, comprehensible explanations for complex phenomena. It’s so satisfying to be able to easily explain something in a sound bite, and sound bites are so much more easily accepted by an audience than some elaborate, difficult collection of details. For example, we often hear homosexual behavior reduced to being a “choice,” the product of a “gay gene,” a “sin,” or something similarly absolute and irreducible…suggesting that it is part of a diverse spectrum of sexual behaviors with multiple causes and that different individuals are different in their behaviors is almost certainly the more accurate description, but that doesn’t satisfy our need for straight, simple, linear causal mechanisms. This is true of most animal behavior, I think—you just can’t crunch it down to one single agent that drives much of anything.

I thought there was one excellent counter-example, though, one that suggested at least some complex behaviors might be reducible to a discrete source: the mating behavior of Microtus voles. It was such a simple, clean story; new results suggest that it was too clean, and that there’s much more to the behavior than was thought.

First, the simple story. There is a gene called the arginine vasopressin 1a receptor (avpr1a). This gene produces a protein that binds to a hormone signal, vasopressin, which is produced by the pituitary gland under a variety of circumstances. A close examination of this gene in voles revealed a variant that had series of short repeated sequences inserted into the regulatory region—an array of short terminal repeat (STR) sequences that were thought to affect the activity of the gene. So far, then we’ve found some voles that have an avpr1a gene with an STR insert (I’ll call them STR+ avpr1a voles), and some voles that lack the insert (STR- avpr1a voles). Variations like this are not surprising.

Now, the interesting part: the vole species first studied showed a strong correlation. The STR+ avpr1a voles, Microtus ochrogaster and Microtus pinetorum, were monogamous species—they got together with a partner and stuck with them for life. The STR- avpr1a voles, Microtus pennsylvanicus and Microtus montanus, were promiscuous and didn’t form that pair bond. The monogamous voles expressed the avpr1a gene in a region of the brain, the ventral palladium, where it was not expressed in promiscuous voles. You should all be thinking that that is an interesting similarity, but correlation is not causation, so what?

The next step was to make transgenic animals, both mice and voles, that contained the STR+ avpr1a. Male mice and Microtus pennsylvanicus were given copies of the STR+ gene, and they then exhibited increased affiliative behaviors—that is, they were more attentive to their mates, with an increase in sniffing (one way rodents show interest is by getting up close and inhaling the aroma of prospective partners) and grooming (another demonstration of affection.) As you might guess, this was a popular subject for a while—a single gene that might make males more affectionate and more loyal to their partner? Oooh, baby, bottle that and put it on the market. (I should clarify, though, that the demonstrations of its effect were all done in transgenic animals, and the gene was present throughout development, so application is a bit impractical.)

Now for the recent complication in the story. A survey of 25 species of voles and other rodents, including the mouse, has found that they all have the STR+ variant of the gene, except for the two closely related species, M. pennsylvanicus and M. montanus, in which this phenomenon was originally described. Loss of the STR insert is the unusual event which occurred just once in this lineage. Monogamy (starred species in the diagram below) is also a minority behavior, so many species are non-monogamous despite having the STR+ avpr1a gene.

(click for larger image)

Segregation pattern of avpr1a STRs and mating system parameters along a molecular phylogeny (cytb) of Microtus and other rodents. Species in which avpr1a STRs are present are highlighted in blue, and species in which they are absent are highlighted in red. Symbols refer to genetic and social monogamy or nonmonogamy. The phylogeny was based on cytb sequences of the analyzed species in comparison with published molecular data [sequences from GenBank (GB)]. Bootstrap values >50 for the neighbor-joining and maximum-likelihood methods are shown above and below the branches, respectively. Species from all continents inhabited by the Microtus genus are included: E, Europe; NA, North America; A, Asia; H, Holarctic.

They also examined a few primates. We humans also have an STR insertion in our avpr1a gene, but it’s in a different location and contains a different repeat pattern. These repeats in regulatory regions of the gene aren’t unusual at all.

Schematic view of STRs in the 5′ region of the avpr1a gene of various mammals. (A) All Microtus species investigated in this study show an array of STRs ˜0.6 kb upstream of exon1, except for two species, M. montanus and M. pennsylvanicus, which lack this element. (B) STRs are present in Mus musculus and R. norvegicus at the same position as in Microtus but have a different repeat motif. An additional short array of STRs is located 2.2 kb upstream of exon1. (C) Homo sapiens, P. paniscus, and P. troglodytes exhibit STR arrays of different lengths located ˜3.2 kb upstream of exon1 of the avpr1a gene. The repeat motifs in these primates differ from those in rodents.

You might be wondering if this means that those original studies with their provocative results were all wrong…and no, it doesn’t imply that at all. It is almost certainly true that avpr1a is one component of some kind of social learning circuitry in the mammalian brain, and tinkering with it can modulate some sociobehavioral traits. That isn’t in question at all. However, what has been tested here is the sufficiency of the avpr1a system for regulating pair bonding behavior, and it clearly is not. There are other neuropeptides besides vasopressin that have effects on social learning, such as oxytocin and dopamine, and they’re all tangled up in rather sophisticated circuits, so there are other pathways and strategies that can generate a preference for monogamy, and other species have used them. There is no single magic circuit to explain a complex behavior.

And sorry, ladies, there isn’t going to be a handy anti-philandering pill, either.

Fink S, Excoffier L, Heckel G (2006) Mammalian monogamy is not controlled by a single gene. Proc. Nat. Acad. Sci. USA 103(29):10956-10960.

Young LJ, Nilsen R, Waymire KG, MacGregor GR, Insel TR (1999) Increased affiliative response to vasopressin in mice expressing the V1a receptor from a monogamous vole. Nature 400:766-768.


  1. Alexander Vargas says

    Interesting how you do expect such stories to be false, but those simple stories are delivered wele packaged and at such high level it just make you wonder if you are being a bit of cynic, too intellectual, deceiving yourself when things can be simpler.

    So it is kind of cool to confirm that those alleged crystal clear stories are, as expected, not so clear after all haha. Specially with this kind of nice, truly evolutionary examples with several species and phylogenies at hand. I think this has happende to me enough times already as to call the next crystal clear reductionist study BS even if it starts out published in the best magazine withe the greatest fireworks.

  2. Carpenter says

    So, originally they tweaked some stuff and got male mice to behave more monogamously, did they also do it female mice? If not, why not.

  3. Classicalclarinet says

    hmm.. if the STR sequences are at the regulatory part of the gene, then how do the STR’s eventually affect the change of the gene?

  4. says

    gee, i never thought of the mating habits of voles when the cats would drag them to the welcome matt. this is quite interesting though….will the fundamentalists start administering ‘monogomy vaccines’?

    good question about female voles.

    and what about vulcans? i’m still wondering about their every seven year mating cycle.

  5. says

    It’s worth noting that such simple stories aren’t just favored by students of biology looking for easy answers – they’re also favored by a system that rewards researchers who “unlock” certain mysteries. (And no, figuring out that a particular system is much more complicated than you expected does not qualify as “unlocking” anything.)

    Which is to say, the original progenitor of the vole story rode that gravy train all the way to the head of the NIMH.

  6. says

    Just looking into bipolar affective disorder, it seems that the promoter region for prodynorphin is polymorphous due to microsatellite hypermutation and the coding region of another gene is involved due to similar variations resulting from a tandem repeat. Moreover, these genes are evidently involved in schizophrenia and certain types of depression, and in the case of schizophrenia, one individual may get schizophrenia and the identical twin might not. Added to this, if one suffers from bipolar disorder, one is more likely to experience auto-immune diseases.

    No doubt this is just scratching the surface.

  7. says

    I’m very relieved to hear this; I’m polyamorous, and the idea of there being a “cure” for something that so many people see as “deviance” is about as terrifying as the idea of a gay gene that can be manipulated to “cure” homosexuality and bisexuality.

  8. says

    which then leads to the question – what about schizophrenic, polyamorous, gay voles? i’m sure the fundies will be after them.

  9. Ned says

    Shouldn’t STR stand for “short tandem repeat” instead of “short terminal repeat”?