Immunology Woo: MHC Mates, Part 2

After last Fridays post on a curiously orchestrated media event for a crappy paper (DUNT TAKE TEH PILL OR U CHOSE BAD BOIFREND!), I decided to bully some of my immuno professors for more information. I mean Ive got MHC experts just down the hall, surely they would know more about this topic!

ERV: “What the hell?? Did you read the news today??”

Professor: *blink*

ERV: “Did you see that crappy paper about humans ‘sniffing’ MHC molecules and women on the pill???”

Professor: *blink*

ERV: *explains crappy paper*

Professor: Its kind of a well known mating trick with mice. Youre trying to get your mice to breed, they wont, so you put a different mouses poop underneath the cages, and suddenly the mice want to mate. Probably has something to do with mice ‘smelling’ a different MHC peptide.”

ERV: “Oh.”

Professor: “But humans dont have a vomeronasal organ.”

One way your body internalizes signals from the environment is through G-protein coupled receptors (GPCR). When receptors facing the environment interact with ligands in the environment, a chemical signal is turned into an ‘electrical’ signal your brain can interpret as a red rose or strawberry ice cream. These G-protein coupled receptors are like chemical sensors.

So just like there are specialized cells in your eyes and nose using specialized GPCRs to detect light or smells, mice (and snakes, and some other animals) have a structure in their noses, the vomeronasal organ (VNO), to detect a different kind of ‘smell’. But the VNO is not just an extension of the nose (think of it as if you had a second pair of eyes that only saw in the UV spectrum). The GPCRs in the VNO do not recognize the same chemicals/molecules as the main olfactory system, and its not connected to your brain the same way as your nose. ‘Normal’ smells go to the olfactory lobe to be sorted into ‘WHOO! Thats popcorn!’ or ‘BLECH! Thats a pig feed-lot!’. Vomeronasal smells end up at the amygdala and hypothalamus.

So its not too surprising that mice and snakes use vomeronasal smells for mating and aggression and stuff the amygdala and hypothalamus control. So why cant humans use our ‘second smell’ for mating too?

Well, thats where we hit that bump in the road.

Humans dont have a vomeronasal organ.

Well, I mean we ‘have’ one like we ‘have’ tails. Its vestigial. It kinda develops when we are embryos, and then it goes away. Sometimes doctors can find it in patients, sometimes they cant (… on the same patient at a later time). But just because we cant see it doesnt mean its not just hiding or shrunk, and still fully functional. Luckily, we have GeneBank now. And we have evolution! A great trick to see if humans still have a functional VNO is to hunt for functional versions of the genes that code for the vemeronasal receptors! If the genes dont code for functional receptors, then there is no friggen way they are relaying information to our brains about our boyfriends MHC genotype (just like a color blind person aint gonna see green).

People have performed that little GeneBank hunt. Turns out about the time primates developed three-color vision and started relying on more visual cues for mating, selective pressure on the vomeronasal receptor genes started to go lax. Thus mice, who use their second smell every day, have >200 genes that code for vomeronasal organ receptors… and humans only have 4 or 5 putative genes, and >200 pseudogenes chock full of nonsense mutations, premature stops, insertions… theyre a mess.

Evilution is waving ‘bye-bye’ to our second-smell past.

So why are studies like ‘TEH PILL MAKE YOU SMELLZ MHC RONG!’ still going on? I have no idea. There must be some evidence that humans can communicate with different chemical signals (ie women living together get on the same menstrual cycle), and some labs appear to be trying to deal with the fact humans dont have VMOs… But the authors of ‘MHC-correlated odour preferences in humans and the use of oral contraceptives’ didnt even try to address the controversy around their field. Not even a reference to ‘Some people think…’.

But they sure had time to orchestrate a massive PR push for their pathetic data.

So like I said before, stupid crappy ‘science reporting’ and stupid crappy research. Ugh.

Comments

#1 ibaien
August 19, 2008

nice work, as always. but hasn’t the menstrual-synchronization thing been debunked?
#2 ERV
August 19, 2008

I have no idea! Its referenced in one of the papers I read that tried to ‘defend’ human VNOers, but Ill look it up!
#3 Jon H
August 19, 2008

“and humans only have 4 or 5 putative genes, and >200 pseudogenes chock full of nonsense mutations, premature stops, insertions… theyre a mess.”

Whew, that’s a relief, sorta. I had a deviated septum op when I was in high school, and after I heard about the old vom organ, I wondered if some vestigial remnant had been cauterized away, leaving me romantically blind.

I guess that’s not it, and I’m just obtuse.
#4 Luna_the_cat
August 19, 2008

Well, but humans *can* distinguish “good” and “bad” smells of potential mates in terms of more than just personal hygeine. And I have seen studies which indicate that women, especially, are able to tell the difference between “normal” male sweat and sweat produced when they guy was stressed or afraid. So what about the possibility that we are getting non-conscious cues from our sense of smell with either the pathetic residual VNO or via our “normal” scent receptors?

No, sadly I don’t have paper refs to hand and can’t promise to find them right away, since we are busy having a server meltdown at work right now and everyone is in a major panic here. But if I happen to run across any in my intermittent perambulations of my archives, will post.
#5 Sili
August 19, 2008

Awesome! I’ve just read the chapter on the nose in Your Inner Fish so I actually have an idea what you’re talking about!
#6 Brian
August 19, 2008

ibaien is right, so far as I recall. Digging around, I found this relatively quickly. It would take me a bit longer to find more, I think.

The money quote in this piece is this:

Popular belief in menstrual synchrony stems from a misperception about how far apart menstrual onsets should be for two women whose onsets are independent. Given a cycle length of 28 days (not the rule�but an example), the maximum that two women can be out of phase is 14 days. On average, the onsets will be 7 days apart. Fully half the time they should be even closer (Wilson, 1992Go; Strassmann, 1997Go). Given that menstruation often lasts 5 days, it is not surprising that friends commonly experience overlapping menses, which is taken as personal confirmation of menstrual synchrony.
#7 Becca
August 19, 2008

Even for standard olfactory receptors, mice have 2.7x as many as humans. Do you think that means Evilution is doing away with our entire sense of smell (some parts faster than others)? Or is this another edition of “Mice =/= furry people”?
(for reference: if mice *were* furry people, we would synch cycles… as an aside, given how controversial that field is, I would neither believe it nor dismiss menstural synchronization out of hand)
I do think some sensory input is probably amgydala-routed. Whether we know the cell surface receptors actually detecting specific odorants, and whether those odorants are related (perhaps indirectly) to MHC, I am unsure of. Of course, subjectively, smells can be very emotional sensations. Including lascivious emotions (or would it be “cuddling” emotions, for this study?).
#8 eddie
August 19, 2008

When I first heard of the paper, I thought ‘I smell a rat’, but no; there goes my VNO as bullshit detector theory.
#9 Brian
August 19, 2008

Yeah, having worked in a teratology lab for some time I can definitely report that when it comes to mating, mice =/= furry people. Like, at all. Or at least, I hope not.
#10 Brian
August 19, 2008

And, of course, I submitted my comment before I meant to. I would add that interested parties look up the Whitten effect, the Bruce effect, and the Vandenbergh effect, all of which make mating mice a royal pain in the ass. But they are interesting in their own right, and indicate that it may be a bit far-fetched to assume that mice and men operate alike.
#11 Tatarize
August 20, 2008

There’s some slight overlap in the molecules picked up by the VNO and the nose proper, but there’s not much to suggest we use that minor pickup for anything.

I’m starting to hate all these other-animal sense organs. It’s like they have some kind of superpower. Seeing ultraviolet, infrared, light polarization, light phase, magnetovision, sensing electric fields… and what do I have on them. I can see red. Some animals can’t see red but I can! Woot, suck that! Can you see that red Mr. Dog? No. Awe. — I guess I also have a very complex language skill but that more of a secondary effect of a powerful neocortex hooked up to all of my brain, so it doesn’t really count (if I wasn’t taught language, I wouldn’t develop it outside of a group). *sigh*
#12 Brian
August 20, 2008

Yeah, I hear you, Tatarize. The light polarization thing made me want to get a mantis shrimp for the longest time. But I think I’d start to become jealous and resentful after a while, as it taunted me with its ability to see polarized light. Also, it could probably take me in a fist-fight.
#13 jdc
August 20, 2008

Nice work. Spotted a link to this piece on the ‘Healthy Distrust’ blog and followed it. No functional VNO – no way the research covered by the Independent was anything to write home about. Simple enough even for me to understand.

PS – like the lolcat-style “TEH PILL MAKE YOU SMELLZ MHC RONG” bits. Nice touch.
#14 S
August 20, 2008

Can someone tell me how MHC molecules are detected by mice? They are cell surface proteins, right? so do whole cells waft into the mouse’s VNO?
#15 Jon H
August 20, 2008

I actually saw a blogger post about this study, and suggest that there might be a connection to the incidence of autism.

As in, birth control leads women to choose ‘bad’ mates, something something something something, autism!

WTF!?!?!
#16 Blake Stacey
August 20, 2008

Uh-oh, Jon H, you know what this means.

Birth control makes women choose mates who vaccinate their children! OH NOES!!!!!!
#17 windy
August 20, 2008

No functional VNO – no way the research covered by the Independent was anything to write home about.

I have to say “not so fast” again. The study didn’t claim that humans sense pheromones via VNO. The experimental design only tested if women find the smell of some men more “desirable” or “pleasant”. Obviously, humans are capable of distinguishing pleasant and unpleasant smells even without VNO, so if MHC affects BO, it’s possible to find some effect.

So, what about Abbie’s argument above, that in any case the smells can’t have an effect on mate choice since humans don’t have the “direct line” of the VNO? I don’t know. But in some fish and birds MHC variation affects mate choice. Fish and birds don’t have a vomeronasal organ.
#18 Monado
August 20, 2008

Humans do so have a vomeronasal organ. They just weren’t looking for them at first. Some experiments have been done with putting pheromones from sweat on cubicle doors in a student residence, and they found that everyone in the res “coincidentally” chose another cubicle except for one guy who remained oblivious. Must have had a stuffy vomeronase…
#19 Homer
August 21, 2008

I’ve studied olfaction for a while now, and I wanted to emphasize a couple points in the comments. Humans do not have a VNO. The VNO in mammals is a small tubular organ lined with VN receptors. It acts like a pump. Thats why dogs are not happy just getting a whiff of another dog’s butt – making that contact helps the VNO pump up heavy molecules (like peptides) so they have access to the receptors. Some humans still have a small pit in their their nose where a VNO may have been once, but no actual organ, and most importantly, no central wiring to the brain. Second, these molecules and “pheromones” in general can be detected by both olfactory systems, the VNO and the main olf receptors. So in mammals with a VNO, the MHC may have VNO action, but can also smell in the normal sense. Humans can discriminate between the smell of 2 transgenic strains of mice varying only at the MHC locus. We do it with our main olf system, the mice use both. Finally, although the human olf receptor complement has been dramatically reduced compared to mice (about 300 functional genes in humans, 2000 in mice), humans have a great sense of smell. Though detection thresholds may be worse and there may be a few specific molecules we can’t smell, overall we have a very broad and sensitive nose. That is probably because its connected to our brains, where most of the cool stuff about olfaction occurs.
#20 Interrobang
August 21, 2008

Humans may or may not have a VNO; I don’t think I need one, since I can smell the Great Red Spot from here, pretty much. Pheromones, you bet. S’one of the reasons I find the smell called “umami” to be so unpleasant — it smells like human sexual secretions with the pheromone kick taken out, and if you ain’t gonna get that, what’s the point? You might as well stick your head up the rump of a civet and be done with it.

Correct me if I’m wrong, but is that Strassman paper actually suggesting that some people’s menstrual cycles last less than five days?! If so, where are those people and what are their names? I and my nine-day menstrual cycle are going to be making a little list; they never will be missed…
#21 Lou FCD
August 22, 2008

Thanks for this, Abbie.
#22 Alan Kellogg
August 22, 2008

The presence of a VNO may be up in the air, but we do have Cranial Nerve Zero. A pair of nerves found only in the head. Called CNZero because we didn’t know about when we started numbering the Cranial Nerves and assigned the olfactory nerves the number one.

But, it’s easy to over look, especially when you don’t want to find it.

The pheromone system isn’t really a sense of smell, it’s a signaling system, a method of chemical communication. Animals produce pheromones to broadcast a signal — fear, friendship, anger — or in response to a signal received from another. We don’t have a VNO because we have additional tools we can use to complement our pheromone system. So when that captive tasmanian devil displays the friendship gape (something, as far as I know, tazzies only do for humans) it serves to reinforce the friend message the animal’s pheromones are sending us.

We lont the VNO because we no longer need it, but it remains useful, and in many cases vital, for our success as individuals and as social animals.
#23 Jared
August 23, 2008

Ok, I’m getting tired of this, as genetics is my friend; if we lack homologous receptors used in MHC-based odor detection, it is highly unlikely that we can detect this. Individual mice never vary ONLY at their MHC loci for several reasons; study basic endocrinology and you’ll discover that with varying scent and behavior can affect sebaceous glands. But I’ll stand by the lack of receptor homology probably means a lack of receptor.
#24 windy
August 25, 2008

Ok, I’m getting tired of this, as genetics is my friend; if we lack homologous receptors used in MHC-based odor detection, it is highly unlikely that we can detect
this.

The VNO-type receptors in humans are nonfunctional, not necessarily all MHC-linked receptors:

Characterization of Clustered MHC-Linked Olfactory Receptor Genes in Human and Mouse

Besides, I’m not sure how this is supposed to work in the various organisms that lack VNO and can apparently detect MHC differences. Perhaps animals can differentiate based on self-similarity, not only by having specific receptors for MHC types.