Ancient and Recent Positive Selection Transformed Opioid cis-Regulation in Humans

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Ancient and Recent Positive Selection Transformed Opioid cis-Regulation in Humans:

…In addition, the pattern of linked nucleotide and microsatellite variation among and within modern human populations suggests that recent selection, subsequent to the fixation of the human-specific mutations and the peopling of the globe, has favored different prodynorphin cis-regulatory alleles in different parts of the world.

John Hawks has detailed commentary. Some info on cis and trans regulation.


  1. I just wonder/ speculate – does this provide some clues as to the universality of mood altering chemicals in virtualy every human society/ culture? 
    If anyone has some info on this I would appreciate the info or the links- i am quite intrigued by the near universality of substance abuse in all societies but havent been able to find any data. 
    sorry about being a little off topic

  2. You can start with A Brief History of Drugs by Antonio Escohotado. A short book with a lot of interesting stuff. Also, check out the archives of Doubt that you’ll find much historical or ethnographic stuff, but it’s possible. 
    Anyone care to speculate what this gene actually does?

  3. darth: 
    I am more intrigued by the biology if there is any, not the history.

  4. vic, if you’re interested in the biology, then is a terrific resource. You should find plenty of good stuff in the FAQs. And, oh yeah, check out Probably the best druggie site that you’ll find on the Web. 
    There are several books on recreational drugs that aim at comprehensiveness, but I find that they’re all dated or contain errors. Books on specific drugs tend to be better. I recommend MDMA edited by Julie Holland.  
    You know, I have drugs to thank for my aspiration to become a scientist! I used to be a know-nothing humanities type. (Now I’m a know-next-to-nothing wannabe science type struggling with summation signs.) If not for the grace of God, I’d be a scum-sucking lawyer right now. A term paper I wrote about the effects of entheogenic drugs, combined with stumbling upon Pascal Boyer’s book Religion Explained … and here I am. 
    Funny thing. Why do the “opioid” receptors have the name that they do? It’s hard to imagine that the receptors are “for” binding opiates. It turns out that the receptors were discovered before their endogenous neurotransmitters. But is it possible in principle for the binding of exogenous ligands (e.g., drugs) to play some role in selecting for or maintaining certain receptors? … There’s this guy named McKenna who has a crazy book called Food of the Gods, I think, that goes off on this idea. I don’t recommend it, but you might find it entertaining …

  5. As I’ve read quite a bit on neurochemistry, I’ll summarize some things about the opioid system here. Dynorphins, the active peptide products of the prodynorphin gene, have highest affinity for the so-called kappa opioid receptor, rather than the mu or delta opioid receptors. The mu receptor has the greatest affinity for morphine, though the other two receptors contribute as well to its effects. Much evidence (search the literature and you’ll find it) suggests that mu receptor activation is necessary for the physical dependence induced by opioids. Interestingly, getting to Darth Quixote’s comment, the kappa agonist salvinorin A from the plant Salvia divinorum, which is potently psychoactive although it has essentially non-existent addiction liability, produces varying subjective effects in humans. In many people, as well as laboratory animals, it produces dysphoric effects, but a few people greatly enjoy the unique state it produces.