This feels like the most sensitive post I’ve ever made. If I could do something better I’m happy to consider it.
There are some fascinating mice I’ve wanted to post about. Mice in which the TrpC2 gene has been deleted (TrpC2-/-, +/- is heterozygous). First I need to do a little set up.
Humans and Trp2C.
It’s about most of the rest of vertebrates vs. “old world” primates (parvorder Catarrhini). The old world primates include gibbons and great apes like us, and they lack a vomeronasal organ and accessory olfactory system as I mentioned in the other post some posts ago. So no pheromone system and other things that this system did for us. But I believe the evolutionary event of TrpC2 wreckage in human ancestors had a significant effect on us for better and worse.
And in that other post I pointed out how the accessory olfactory system and pheromones themselves are devoted to a range of behaviors beyond mating. Going into predator and prey or food, and a large range of information about your own kind like age, sex, relatedness, health status and more. Whole information channels now missing, but with still existing brain hardware downstream from that olfactory system.
Trp2C is a cation channel protein, “transient receptor potential 2C” (Ca2+, Na+). It is located in the same part of vomeronasal sensory neurons as the vomeronasal olfactory receptors and is part of the signalling system that activates the neuron during signal transduction. In humans this is a pseudogene, it contains a bunch of extra termination codons that severely truncate the protein making it non-functional. It’s an obvious experiment to delete the gene in a model organism like the mouse and see what happens and so some scientists did that.
Before I introduce the mice I want to emphasize that humans have a whole evolutionary history that includes other accessory olfactory pseudogenes, and other changes I think of as “things sandwiched between stimulus and impulse”. These mice are creatures we made in a lab without the 25-40 million years of extra evolution since we lost our Trp2C. There will be implications for good and bad things.
The TrpC2 deletion mice.
These mice lose their social aggression for one thing. They’ll defend themselves if attacked but don’t do any attacking themselves. Males stop fightng intruder males. Females stop fighting intruder males during lactation. Males stop being aggressive towards juveniles. They don’t seem to form dominance hierarchies (as measured by urine marking patterns, the dominant mouse gets to go everywhere, everyone else goes in a corner). TRICK or TRP? What Trpc2−/− mice tell us about vomeronasal organ mediated innate behaviors. Yu 2015
Females don’t engage in nest building as often and don’t nurse as often, but offspring numbers are the same and they have similar body weight so maybe they nurse more effectively. Trpc2 gene impacts on maternal aggression, accessory olfactory bulb anatomy and brain activity. Hasen 2009.
Males care for offspring more, though not to the level of females. Vomeronasal signal deficiency enhances parental behavior in socially isolated male mice. Orikasa 2017
Examples of lost behaviors? TrpC2-/- mice can’t detect sick mice anymore for one thing. Sensing and avoiding sick conspecifics requires Gαi2+ vomeronasal neurons. Weiss 2023.
And then there’s sexual behavior.
This paper describes the big ideas. The De-Scent of Sexuality: Did Loss of a Pheromone Signaling Protein Permit the Evolution of Same-Sex Sexual Behavior in Primates? Pfau 2021.
The first thing to mention is that all of these behaviors were already present at low levels in wild type mice (as they are in primates with an accessory olfactory system). These studies describe increases in rates of various behaviors. The same goes for the previous behavior but I wanted to make the point here. There’s no “gay gene” here since the same sex behavior was already there. It’s more like existing sex specific behaviors increased rates and spread out to both sides once they lost olfactory control.
Both male and female TrpC2-/- mice will mount males or females during intruder experiments instead of fighting. At other times too but this was the really noteworthy experiment since fighting an intruder is the typical response of the non-mutant mice.
It gets more detailed. Female TrpC2-/- mice also scent mark like males, vocalize like males, engage in exploratory anogenital sniffing like males (which males usually do during courtship), and they do this thing where they lift up the other mouse’s rump with their nose like males. The behavior between the male and female TrpC2-/- mice get described differently in the literature early on with the male mice merely engaging in same sex behavior but the females show “male type sexual behaviors”. A functional circuit underlying male sexual behaviour in the female mouse brain. Kimchi 2007.
The tough subject, the bad one.
Trigger warning: implications about child sexual abuse.
A final sexual characteristic of the TrpC2-/- mice is they no longer respond to a protein secreted from juveniles that suppresses such behavior (ESP22). These mice were used in the following paper to study this phenomenon. A juvenile mouse pheromone inhibits sexual behaviour through the vomeronasal system. Ferrero 2013. These mice express sexual behavior towards juveniles at higher rates than wild type mice. This is the tough subject because it’s explanatory of problems we’re dealing with as a society, just as the other observations are explanatory of things that aren’t problems because of consent and similar developmental stages between individuals.
This is explanatory for why should such things even exist. It’s in the same box as murder, it’s possible for some of us, but implicitly harmful. A violation of power. I’m of the opinion that in order to control ourselves as a group it helps to understand ourselves as a group and I believe these mice help there.
could these altered mice form a long-term population with the same properties, or would they decline and disappear? if they persisted, might they have “cultural evolution” to offset undesirable traits they’ve acquired? those are experiments that could be run. almost all human cultures support male aggression and dominance, have taboos against homosexuality and pedophilia, to varying extents. those are cultural traits, which makes them subject to change, but cultural traits are also subject to selection – ones that make the society flourish survive, ones that harm it can be selected against. it seems to me that even if vomeronasal breakage makes us have higher rates of certain traits – good neutral and bad – we may have already adapted to that with different, less effective (but still somewhat effective) ways to achieve the same ends – good neutral and bad.
it’s funny to imagine knuckledraggers taking this science and using it to justify genetically altering the whole human race to use pheromones and buttsnuffing again. woof.
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honestly, i’m not sure there are significant implications regarding human behavior here. explanation of why apes have higher rates of certain behaviors than lemurs, ok, but these things are always subject to sociology, psychology, ethics, philosophy, all that human cultural shit. ejemplo: strongly patriarchal societies now (as opposed to ancient greece) tend to suppress homosexuality, but increase pedophilia. see various american cults like the flds or quiverfull that have patriarchs, justifying child marriage, or just turning rural compounds into child rape camps. if male aggression is negatively correlated with pedophilia in these mice, why are they positively correlated in some humans? the biology is having less effect than the sociology. maybe it explains why we regulate our society with culture more than instinct – we lost a powerful vehicle for instinct and had to replace it with something.
You mention that there has been 25-40 million of years of evolution since catarrhines lost trpC.
My initial response is to look at the behavioural differences between chimpanzees and bobobos, with only a few million years of evolution between them, ask whether any initial effects of the loss of trpC have been drowned by the subsequent changes.
It’s hard to say if these mice could survive as a population.
I’m not sure how to apply culture and cultural evolution to mice. They don’t have much in the way of abstraction and symbolism.
Their vocalizations might be a place. Without the vomeronasal organ and accessory olfactory system the feelings and instincts associated with it could be tied to other senses and matched with sounds perhaps.
We certainly have evolved in ways that matter to loss of those systems. The input to the amygdala for the non-olfactory senses is much larger in primates and especially humans. (lateral nucleus of the Amygdala). I need to look up how that gets connected to the same feeling and action centers I posted about previously.
I once joked on discord “how dare we abandon the butt-sniffing ways of our ancestors!” while posting about vomeronasal detection of fecal molecules.
To me the significance is in the potential origin of some of our impulses. Or intensification of impulses absent a system that inhibited them until needed. You are right about other factors affecting things in humans. I think the same impulses are strongly wired into the rest of the senses, especially audio/visual for things that drive patriarchal impulses and aggression in males, or men. There are differences in circuits between male and female mice for aggression and defensive behaviors (subject to low levels of flipped patterns maybe).
These are social structures that try to control who gets to be aggressive and how. The resulting differences will have their own differences in the meat computer. Powerful men allowed to be aggressive and dominant have more opportunities to abuse children. The culture sets up how the impulses are used.
I agree society has a stronger affect here.
TrpC2 changes would be part of the background of what we feel. An increase in some impulses due to loss of inhibition from the lost olfactory system.
I think the difference between chimps and bonobos have cultural elements too, and bonobos aren’t devoid of aggression. The momentum of choosing sex in situations and the momentum or choosing aggression in situations.
I thought of something else.
A gene deletion here produces changes in the hardware. “What it is/feels like” subject to developmental differences. The human cultural shit is a “how it is used” issue. It shapes what we do with the feelings and actions.
lot of food for thought but i’m not feelin hungry to get my think on.
“The tough subject, the bad one.”
“This is the tough subject because it’s explanatory of problems we’re dealing with as a society,”
First thing, thank you very much for providing this info. It is very important. Now for my criticism of your tiptoeing around the subject:
Yes, I am sure a trigger warning here is very necessary for some people, all well and good. BUT, for those of us who don’t have PTSD for this subject, it really shouldn’t be whispered. The best way to solve a problem is for all people to discuss it freely and openly. If you want to protect your house from burning down, you need to learn the conditions that make fires possible. Avoiding the subject just leaves you more vulnerable.This info is utterly new to me, and I expect it is utterly new to 99.999% of the population, but we need to learn it. I am just spitballing here, but ISTM it kinda puts homo sapiens into the same position WRT sexual abuse of minors that children of alcoholics find themselves in WRT alcohol abuse: as individuals, children of alcoholics have a wide range of reactions to alcohol in their environment, but as a group they have a greater attraction to alcohol than others outside the group. And the sensible way to deal with this fact is to acknowledge it and discuss it openly and unashamedly.
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“It’s in the same box as murder, it’s possible for some of us,”
I REALLY disagree with this sentiment. Given the evidence I see in both reality and in fiction, I think it is very apparent that ANY ONE of us could become a murderer, given sufficient impetus. Now, it MAY not be true that any one of us potentially could sexually abuse a minor, but once again I see evidence (Matt Gaetz, Jeffrey Epstein, Ghislaine Maxwell, Roman Polanski, Mary Kay LeTourneau, etc, etc) that it is much more common than most of us are willing to acknowledge.
No tiptoing here, I’m trying to be sensitive and trigger warnings help with that. With or without the warning you still get the info and the ones with PTSD can take a moment.
Otherwise I agree with being able to openly discuss it.
Let me describe the box murder is in here better. First murder is a subset of killing and I wouldn’t see killing in self defense the same. Still, unjustified killing is natural and a thing to oppose. That’s the similarity I use to put child sexual abuse in the murder box. I could end up in the killing for self defense box.
The last time I looked 5% of people had a capacity for minor attraction and 0.5% were exclusively attracted to children. I think there’s an imprinting effect at a stage of development we don’t fully understand that can lead to this and fetishes (not that fetishes are all bad, it’s the point about developmental windows and imprinting)