Love Is A Virus

prairie_vole_1.jpgLove demands an explanation. Less than 5% of mammal species live monogamously, with males and females staying together beyond mating, and fathers helping mothers care for babies. We humans aren't the most monogamous species of the bunch, but we're closer to that end of the spectrum than the other end, where mating is little more than ships bumping into each other in the night.

A biological explanation for love--as with any biological explanation--has two levels. On one level are the molecular circuits that produce love, and on another level are the evolutionary forces that favor the construction of those circuits in the first place. It turns out that in this case one of the best guides to both levels of explanation is the vole.

The prairie vole is a five-percenter. When a male prairie vole mates, something happens to his brain. He tends to stay near her, even when other females are around, and then helps out with the kids when they arrive--grooming them, huddling around them to keep them warm, and so on. By contrast, the meadow vole, a close relative, is a ninety-five percenter. Male meadow voles typically couldn't care less. They're attracted to the scent of other females and don't offer parental care.

Scientists have searched for years now for the molecular basis for this difference. One promising candidate was a molecule called the vasopressin V1a receptor (V1aR). In certain parts of the brains, male prairie voles produce more V1aR than meadow voles. To test whether this difference had anything to do with the dedication of male meadow voles, Larry Young of Emory University and his colleagues injected a virus carrying the V1aR gene into the brains of medow voles. As they report today in Nature, the virus caused the meadow voles to begin huddling with their mates almost as loyally as prairie voles.

So what happened? It seems that for prairie voles, love is a drug. When male prairie vole mate, their brains release a chemical called vasopressin. Vasopressin does a lot of things all over the body, such as regulating blood pressure. In the brain of prairie voles, it latches onto vasopressin V1a receptors that stud the neurons in a region called the ventral palladium. This region is part of the brain network in vertebrates that produces a sense of reward. Young and company propose that the memory a male forms of mating with the female gets associated with her fragrance. Later, every time he gets a whiff of her, he feels that same sense of reward. This brain circuit is also responsible for the high from cocaine and other drugs--as well as the addiction. Even looking at drug paraphernalia can make an addict feel the old cravings, because his memories are tinged with the high.

By contrast, male meadow voles have relatively few vasopressin receptors in their brains, so that vasopressin released during sex doesn't switch on the same circuit and they never develop the same memories. And so, to them, the smell of their mate produces no special feeling. In an accompanying commentary, Evan Balaban of McGill University in Montreal says that V1a receptors may be "the adjustable nozzle atop a social-glue dispenser in the mammalian brain."

You can almost see the spam already on its way to your mailbox:LADIES! Trying to land Mr. Right? Just inject our new Vaso-Love virus into his brain before your next date, and HE WILL BE YOURS FOREVER!!!

Don't buy it.

It's true that much of the circuitry in our brains is similar to that in voles. And we also produce vasopressin and other neurotransmitters that are associated with love and other feelings. That's because we share a common ancestor with voles that had the basic system found in the heads of both species. But since our two lineages diverged, perhaps 100 million years ago, the systems have diverged as well. The bonding in voles depends on the male smelling the female. That's not surprising, given that voles and other rodents have an exquisite sense of smell. We don't; we're more of a visual species. Differences like these mean that what works for the vole probably won't work for the human. (Even among rodents, Vaso-Love doesn't work: gene-therapy experiments--in which the prairie vole gene has been injected into mice and rats--haven't altered their behavior.)

Even if Vaso-Love won't be hitting the patent office anytime soon, Young's research can shed some light on our own love lives. That's because he and his colleagues have discovered a fascinating difference between the V1aR gene in the two species of voles. All genes have a front and back end. At the front, you typically find a short sequence that acts as an on-off switch, which can only be operated by certain proteins. In praire voles, this front end also contains a short sequence that is repeated over and over again--known as a microsatellite. In meadow voles, by contrast, the microsatellite is very short.

Somehow the microsatellite affects how the gene is switched on in each species. A long microsatellite produces more receptors--and a loyal male--in the prairie vole brain than in a meadow vole. While it isn't clear how microsatellites alter the amount of V1aR produced, what is clear is that it is, evolutionarily speaking, easy to go from one behavior to the other. The same gene produces different behavior simply due to being common or scarce. Moreoever, microsatellites are famous for their high rate of mutation. That's because the DNA-copying machinery of our cells has a particularly hard time copying these sequences with complete accuracy. (Just imagine typing a copy of that manscript in The Shining, filled with "All Work and No Play Makes Jack A Dull Boy," over and over again. It wouldn't be surprising if you discovered once you were done that you missed a couple of those sentences, or added a couple on.) Since microsatellites control behavior, it's relatively easy for new behaviors to evolve as these microsatellites expand and contract.

This sort of flexibility can help explain the fact males and females of closely related mammals (such as the prairie and mountain voles) often evolve different behaviors towards each other. Here is where an explanation of love shifts levels, from molecules to evolutionary forces. Monogamy and fatherly care are favored by natural selection in certain siutations, and not in others. Scientists have identified a lot of factors that can produce a shift from one to another. One particularly unromantic force for monogamy is known as mate guarding. In some species, females can mate with many partners and then choose which sperm to use. If a male guards a female after mating, she'll have no choice but to use his sperm. Young's research suggests that mammals can switch pretty readily from one sexual behavior to another pretty quickly thanks to minor, common mutations.

Primates--our own branch of the mammal tree--seem to fit the general pattern. Marmosets, which pair up for years, have lots of V1a receptors, and promiscuous macaques don't. It will be interesting to watch what scientists find when they look more carefully at vasopressin in the brains of humans and our closest living relatives, chimpanzees and bonobos. As a rule, monogamous species tend to have males and females of the same size. In other species, males tend to fight with one another to mate with females, which gives big males and edge over smaller ones. Male chimps, for example, are bigger than females. Since our ancestors split with those of chimps, we became more monogamous, so that males are much closer to females in size.

One leading hypothesis for this shift has to do with our big brains. The human brain grows at a tremendous rate after birth, using up lots of energy along the way. Human children are also more helpless than other apes; a baby chimp can quickly clamp onto its mother and hang on. The care and feeding of hominid babies may have gradually required the work of two parents, which would have favored monogamy.

Not that monogamy became a hard and fast rule, of course. Even within the loyal prairie vole species Young has found variations. Some of them produce more vasopressin receptors, and some fewer. Likewise, some of them are more monogamous than others. On both counts, the same goes for humans. It's not surprising that humans should vary in their receptors, since microsatellites mutate so easily. Mutations that knock out most of the microsatellites have even been linked to autism, which is, among other things, a social disorder that makes it difficult for people to form deep attachments. Vaso-Love gene therapy may not get you the perfect man, but what if measuring how many V1a receptors a man has in his ventral palladium may give you a hint of whether he's going to stick around? Will a PET scan some day become part of the modern courtship ritual?

Update 6/17 5:20 pm: Be sure to check out Bornea Chela's Jason South's comments. He brings up some important points that are also discussed in the original papers.


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I love reading your stuff. This one made me think of the poem I wrote on how the viruses cultured us (rather in the manner of The Botany of Desire) for their own purposes. I thought you might enjoy it:


New snow is floating down dark on the old --
The shadows are deep. I think of the viruses,
Their dominion of man, how they raised him
In their conceit, and watched as he ran amok
Raising up civilizations image
In their own (the viral paradigm divine)
Three billennia ago it happened,
They devised the plan: Let the apes grow
Fringey types, let Sapiens take dominion,
Let him -- survive. As aphids to ants theyll be --
(This was, of course, long before aphids;
They were conversing in metaphorese
The language of viruses long, long ago.)

In a fission they saw it, saw him rise
To Parnassus, test the bonds that bound him
Discover powers fermentation;
Saw him, finally, discovering them
(The viral invasion, the ooze sublime)
There in the patterns deepening endurance,
In apocalyptic schism they triumphed,
Preoccupied: As molds to gravity
They shall to us be, gravely intent
On the license our laws have so inspired --
They saw him in their holy image shine.
Like old snow brightened by new, the viruses
Gleam in the shadows I watch, and know.


Thanks for your many fine thoughts--keep them coming.

Mary (mother of nine)

So that's it! I'm not afraid of commitment, I'm just V1a receptor challanged.

By Carl Buell (not verified) on 16 Jun 2004 #permalink

I really enjoyed this post and have a few comments and/or quibbles.

1) Most behavioral ecologists now view parental care as a phenomenon that is separate from the mating system. For example, a somewhat recent comparative analysis found that monogamy has evolved more in the absence of paternal care than in lineages with paternal care. And in those latter lineages, paternal care seems to have evolved after monogamy.

2) The vole result is extremely interesting, but most monogamous mammal species are even more flexible in their mating patterns than voles
and thus not likely to exhibit the same molecular
control of mating behavior. Many other species can shift their mating system from monogamy very quickly when ecological conditions change. I just finished reviewing a newish edited volume on monogamy for the Journal of Mammalogy, and it turns out that many "monogamous" mammals live in closely associated male-female pairs
(social monogamy), but frequently mate outside of the pair. For example, 44% of fat-tailed dwarf lemurs were fathered by males other than their mother's social partner.

One last note...the hormone oxytocin is also likely to play a significant role in pair affiliation and the maintenance of monogamy.

It's interesting that the monogamy/promiscuity difference is framed as a difference between the males. Did they look at how the female voles feel about monogamy? Being able to create monogamy by only treating the males suggests that the female meadow voles aren't interested in the promiscuity scene, and are thus happy when these scientists get ahold of their mates, but out of luck otherwise. In which case I feel sorry for most of the world's female meadow voles.

Is the finding that most "monogamous" mammals aren't really that monogamous all that surprising? That's been known in birds for years. Did we really expect mammals to be all that different?

Re gwangi:

Perhaps the finding that monogamous mammals exhibit extra-pair paternity isn't surprising...but then the challenge becomes explaining why they bother with social monogamy (living with a partner on the same territory beyond mating periods) at all.

> Mutations that knock out most of the microsatellites
> have even been linked to autism

Can you point me to some literature on this, please? Do you mean mutations that knock out microsatellites across the entire genome? Fascinating if so, but a quick Google didn't find anything. And I think I must misunderstand, because knocking out all microsatellites would make linkage analysis (which would direct us toward the mutations) next to impossible.

The vole paper in Nature brings this autism connection up, and cites the following paper:

Mol Psychiatry. 2002;7(5):503-7.
Transmission disequilibrium testing of arginine vasopressin receptor 1A (AVPR1A) polymorphisms in autism.

Kim SJ, Young LJ, Gonen D, Veenstra-VanderWeele J, Courchesne R, Courchesne E, Lord C, Leventhal BL, Cook EH Jr, Insel TR.

Laboratory of Developmental Neuroscience, Child and Adolescent Psychiatry, Department of Psychiatry, University of Chicago, IL 60637, USA.

Impairment in social reciprocity is a central component of autism. In preclinical studies, arginine vasopressin (AVP) has been shown to increase a range of social behaviors, including affiliation and attachment, via the V(1a) receptor (AVPR1A) in the brain. Both the behavioral effects of AVP and the neural distribution of the V1a receptor vary greatly across mammalian species. This difference in regional receptor expression as well as differences in social behavior may result from a highly variable repetitive sequence in the 5' flanking region of the V1a gene (AVPR1A). Given this comparative evidence for a role in inter-species variation in social behavior, we explored whether within our own species, variation in the human AVPR1A may contribute to individual variations in social behavior, with autism representing an extreme form of social impairment. We genotyped two microsatellite polymorphisms from the 5' flanking region of AVPR1A for 115 autism trios and found nominally significant transmission disequilibrium between autism and one of the microsatellite markers by Multiallelic Transmission/Disequilibrium test (MTDT) that was not significant after Bonferroni correction. We also screened approximately 2 kb of the 5' flanking region and the coding region and identified 10 single nucleotide polymorphisms.

The shift from female promiscuity to female fidelity because of male guarding is a result of evolution only if genes mutated to produce guarding behaviour, isn't it? Were there genes inclining males to guarding behaviour?

Also, it was mentioned that the vaso-aphrodisiac is probably not going to work on humans because we do not have a highly developed sense of smell. But perhaps vasopressin released will still allow couples to form deep attachments because of the visual memory of one's partner, probably no less unique in sight than a praire mole is in smell, during mating? Well, if visual associations do not work, perhaps a personalized blend of perfume during sex does?

The Times of London recently carried an articlw which said that mountain voles had the highest rate of sex (in the mating season) in the animal world. Do you know if this is true? And can you help with an e-mail address, even if not as entertaining as yours?

Thanks, FH.

By Francis Hitching (not verified) on 06 Aug 2004 #permalink