Epigenetics ain’t magic


I just got a notice of an Epigenetics Conference in Portland, Oregon. It made me cringe. It’s infuriating because epigenetics is actually a very important concept in development, but there’s this terrible misperception among the public that it’s a magical shortcut for evolution. I was also a bit primed for it by the mention of epigenetics on Larry Moran’s blog.

The Humanists of Greater Portland™ is supporting the 2014 Epigenetics Conference being held on Saturday 5 April 2014. Epigenetics is a relatively new field of science that looks at how the environment affects one’s genetic make up. In former times, it was thought that it took generations to change one’s genetic make up but studies now suggest it can happen over a matter of weeks or months. What one eats, their environment, their activities etc. all can alter ones genetic make up and this can greatly affect one’s health. Even the environment of the mother can affect the genetic make up of the baby in the womb.

No, it’s not new. Conrad Waddington coined the term “epigenetics” in the early 1940s. He was explaining how development is modulated by gene regulation, and that there is a multigenerational pattern of restriction of cell fates within a lineage…and that’s a concept that’s at least as old as Wilhelm Roux.

It’s broader than just environmental effects. We can talk about epigenetic modification within an embryo, as a consequence of a clocklike sequence of switches, for instance. It really is a well-known, long studied developmental process.

It does not change the “genetic makeup”. Epigenetics affects the expression of genes without modifying any sequence information. Thinking that it represents rapid evolutionary change is the major misconception that leads people to think the timing is somehow radical. It isn’t. A mutation changes the “genetic makeup” of a cell — for realz — in a fraction of a second. Get up and run a lap around the room, and you’ll get a rapid change in your physiological state in a fraction of a minute. Move from your flatland home to Denver (or vice versa) and you’ll get long term changes to the constitution of your blood in a matter of weeks. None of these represent a revolution in how we think about evolution.

You want to greatly affect your health, quickly? Don’t drink any water for a day. Or drink a couple of Big Gulps worth of sugar water. That’ll have about the same effect on evolution as epigenetic modulation.

Fortunately, it’s just the general blurb for the conference that set my teeth on edge. The descriptions of the presentations sound much more focused and of reasonable and appropriate scope. It should be informative. But please, pop culture summaries of epigenetics make PZ cry.


Some people are thinking I’m denying any role for epigenetics in evolution. No — it’s just not the role some less informed people think it is. What epigenetic modification does is broaden the range of phenotypes produced by a given genotype, allowing more genetic variation to persist in the population. That surely does have some effect on evolution, but it’s somewhat more indirect than the Lamarckian mode pop culture assigns to it.

It’s one thing that allows genetic assimilation to occur, for instance. But if you think people misunderstand epigenetics, just wait until you hear what they say about genetic assimilation.

If you’re still baffled, I wrote up an introduction to epigenetics a while back. I’ve also got a couple of examples of genetic assimilation.

Comments

  1. microraptor says

    I’ve met a few of these people before, I think (I’m pretty sure they’re from the same group).

    Really pathetic folks- they were busy talking about magic epigenetics and that awful What The Bleep movie (one of them claimed to have been involved in it), and it was obvious that none of them had even a high school understanding of any field of science: they were talking about new age crystal vibrations, and how heavy metal music was so destructive to you because the size of the sound molecules were so huge. I facepalmed so hard I almost gave myself a concussion at that point. If I’d had my iPod on me, I probably would have tried firing up some Motörhead.

  2. gmacs says

    Correct me if I’m horribly wrong, but aren’t epigenetic changes (methylation or acetylation of histones, eg) somewhat heritable, but reversible? Thus they would not have a lasting effect on evolution.

    I remember something recently, I think even in a scientific publication, using epigenetics as a kind of tongue-in-cheek vindication of Lamarck.

    I should know this better since I work next to a bunch of people who study histone modifications.

  3. Bob Dowling says

    But please, pop culture summaries of epigenetics make PZ cry.

    Do you have an alternative source of information for a physical scientist / mathematician / IT bod (no biology since high school) who was taught (probably dodgy) genetics in 1980/81 and never met epigenetics at school (even if it was discovered in the 1940s).

    I say “probably dodgy” because it never got beyond single gene dominant/recessive traits and Mendel’s peas.

  4. woozy says

    I remember something recently, I think even in a scientific publication, using epigenetics as a kind of tongue-in-cheek vindication of Lamarck.

    Was this Science News Feedback section?

    Lamarckism not quite revived

    Laura Sanders described mice passing on the fear of a smell to their offspring in “Fear can be inherited” (SN: 1/11/14, p. 13).

    “Isn’t that Lamarckian evolution?” e-mailed Paul Hyer. Not exactly, Sanders says. …

    Epigenetics… has given a glimmer of hope to die-hard Lamarckians. Epigenetics does allow traits acquired during an organism’s lifetime to be passed on to offspring. …, the process boosts genetic variation overall, but does not promote specific changes as Lamarck might have argued. Those variations then become fodder for natural selection to act on.”

    I’m not a biologist and wasn’t familiar with epigenetics. I found the whole thing very confusing. Still do.

    Maybe the information molecules of epigenetics are too small. Perhaps more heavy metal molecules will will act as a filter to keep them in.

  5. carlie says

    No, it’s not new. Conrad Waddington coined the term “epigenetics” in the early 1940s.

    That’s totally new, ya whippersnapper! (paleontologist)

  6. Thumper: Token Breeder says

    OK, let’s see if I’ve understood this correctly.

    Epigenetics is the expression of a previously dormant gene due to new environmental influences, right? So, for example, when you ascend to a significantly higher altitude and stay there for a while, after you “acclimatise” your blood has become more efficient at transporting oxygen. Obviously for this to happen you must have had the necessary genetic information already, but presumably the resources it takes aren’t worth expending at lower altitudes. So it takes a change in the environment before the expression of that gene manifests.

    Assuming I’ve understood that correctly, it seems a fairly simple concept on the face of it; and quite clearly not evolution.

  7. azhael says

    @7 Thumper

    Epigenetics is the expression of a previously dormant gene due to new environmental influences, right?

    If i remember correctly, epigenetics is any modification of gene expression, that is stable and heritable after cell divission, which doesn´t involve any change in the genetic sequence. That includes activation of supressed genes but also supression of genes, modifications in levels of expression, chromosomal inactivations and many other phenomena.

  8. opposablethumbs says

    From what I can remember, an example of the kind of research being carried out in CH Waddington’s department or rather, perhaps, by some of his successors was taken up by those concerned about the effects of environmental pollutants – and (ultimately) the importance of not letting industry get away with dumping crap in watercourses. Effects on the foetus was one aspect of it. I think those doing the work would all have been mightily displeased by pop culture misrepresentation.
    http://www.iss.it/binary/publ/cont/Pag147_152Vol29N11993.pdf
    Wow, I hadn’t thought about that in a long time …

  9. DonDueed says

    @opposablethumbs:

    That paper was about bad reactions to environmental aluminium.

    Fortunately we don’t have that element here in the colonies.

  10. Thumper: Token Breeder says

    @azhael

    That includes activation of supressed genes but also supression of genes, modifications in levels of expression, chromosomal inactivations…

    Of course, that should have been obvious. Thank you.

  11. skasowitz says

    In classical genetics you observe a phenotype to draw some conclusion over the hereditary component, the genotype. Waddington proposed this concept of the epigenotype which connects developmental processes relating genotype and phenotype. He defined the study of relating causal mechanisms of inheritance to biological development as epigenetics and invoked a role for the environment in inducing alternative phenotypes.

    The term gradually became conflated with the definition used by David Nanney with epigenetics describing cellular heredity that is not based on DNA sequence.

    It isn’t a new field and studying it will not show you the 7 simple steps to unlock the Secret Potential of your DNA.

  12. opposablethumbs says

    Yes, I just about remember hearing about the aluminium sulphate (???) spill that aroused concern (I think it was in Wales. My recollection is pretty dim, tbh).

    we don’t have that element here in the colonies.

    Wot, no aluminium? (or even aluminum? :-) )

  13. opposablethumbs says

    Oh, and not massively OnTopic either, sorry – it was just seeing Waddington’s name that reminded me.

    Cool thing: not many people know this, but Edinburgh University has, somewhere, probably stashed away in some secret dusty filing cabinet, a whole set of portrait sketches of Waddington done as pastiches in the styles of famous artists (there’s a “Chagalle”, a “Henry Moore”, an “El Greco” and several others …) which were given to him as a retirement present. He is smoking a pipe in every one :-)

    /derail

  14. says

    The book I am still not quite done reading calls this stuff “pseudo-Lamarckian”. I.e., the environment, and other factors can have a direct, inheritable, effect on offspring, but **only because** mechanisms evolved, through actual normal evolution, to provide the means to do so. Whether or not such change in expression actually has the capacity to, say.. down regulate a set of genes far enough that some of them become disabled, and then lost, or not, might be an open question, but, other than, say, immunity, which does seem to work by “stealing” data from the environment, to make alterations which can be passed on, at least via breast feeding, or the like, none of it is fully Lamarckian, in any way at all.

    So, yeah.. there are some truly bloody clueless people out there, holding on to this silly nonsense.

  15. says

    I did my postdoctoral work in Waddington’s institute in Edinburgh in 1967-1968, and was once introduced to him and got to talk to him over lunch. He gave the impression of great force of will. The unit, the Institute of Animal Genetics, was a center for excellent work on quantitative genetics, plus some very interesting molecular genetics. However there was rather little work done there following up on Waddington’s concepts. The paper cited by @opposablethumbs is not from that institute, but from the Institute of Cell, Animal, and Population Biology, which was the successor of the Zoology Department and was several buildings away.

    Waddington was interested in a synthesis of art and science, and was always having reproductions of art works hung around the building, and he had an abstract sculpture put on the lawn outside. There were some rather merciless and funny parodies of all that by some the students. I did not see the portraits of Waddington in the styles of various famous artists, mentioned by @opposablethumbs, but they would have been in that tradition.

  16. carlie says

    One of the many reasons I love this blog so dearly: people like Joe Felsenstein just drop by to comment now and again.

    Wow.

    :)

  17. woozy says

    @7 and @8.

    Okay, If anyone has time and is willing to speak to me like I’m five I’d appreciate it:

    Okay, environmental factors affect phenotype. Sure, I can buy that. But how can these traits be inheritable? If epigenetics is “any modification of gene expression, that is stable and heritable after cell divission, which doesn´t involve any change in the genetic sequence” I don’t understand/never learned how anything can be inheritable if it’s not in the genetic sequence.

    In thumper’s example, the gene to process oxygen efficiently gets “turned on” after being dormant. Okay, but what “keeps” it turned on and if (hypothetically) this trait can be passed on to offspring (if not this particular trait some other trait) how does the “turned on”-ness of the gene get passed? I’m very confused (as I imagine most five year olds would be).

    Can someone help me out?

  18. says

    I live in Portland, which is increasingly a mecca (not literally) for woo woo and New Age thinking. The anti-accine stuff is big around here. On the plus side, this event is hosted by Friendly House, which does some great social service work and has a food bank, etc. It’s in a swanky part of town.

  19. Bob Dowling says

    Of course, if I had read the article carefully, I would have spotted PZ’s reference to his own introduction to Epigenetics. Sorry.

  20. opposablethumbs says

    they would have been in that tradition.

    They were an affectionate gift to him from a member of staff, given to him at his retirement party. I didn’t know there was a tradition! But I imagine he must have been a professor with whom a lot of people valued working.

  21. woozy says

    Of course, if I had read the article carefully, I would have spotted PZ’s reference to his own introduction to Epigenetics. Sorry.

    I believe that was an addendum added after some responses such as yours and mine. It think it probably wasn’t there when you first commented. (Although it probably was at the time of my comment.)

    It was a helpful introduction. I need to digest and think it a bit but it helps me with the basic concepts I was lacking.

  22. Thumper: Token Breeder says

    @woozy #19

    I imagine it’s to do with economy of resources. In my example, you always had the ability to make that extra-efficient blood (I’m pretty sure you just make a lot more red blood cells). But your body has finite resources, and those resources were needed for other things. Iron, for example, is used to make red blood cells, but also in a number of other processes. Because the resource is finite it’s a zero-sum game, so using more of the iron to make blood cells means those other processes suffer. At low altitudes you get plenty of oxygen with “regular” blood. At high altitudes you don’t, so your body transfers those resources to blood cell production, allowing those other processes to become less efficient in order to make oxygen transportation more efficient, because that’s what’s needed to allow your body to function at optimum levels. A change in environment necessitates a change in priorities. A child would inherit the ability to create that extra-efficient blood, but their body would not do so unless it was necessary because to do so would allow other processes to suffer.

    Does that help? I’m hardly an expert myself.

  23. Hobbes LeGault says

    I’m actually looking at the evolution of alternative RNA splicing as part of my dissertation, and the fact that this conference is looking at epigenetics as the mechanism of evolution rather than something that can evolve is… interesting.

    (Also, if anyone has any pointers to recent research on the evolution of various epigenetic markers, I’m doing a lit search right now and would appreciate new stuff!)

  24. woozy says

    @24.
    Thanks for responding. My question was really one of how “heritability” works (especially between generations). PZ intro and rereading other links over and over have given me a vague idea of how it works. Maybe. I just need to chew on it.

    As a biology neophyte, the obvious question that comes to mind is “Well, can acquired traits be inherited or not?” and so I’m guessing the answer is sometimes but they don’t “evolve”; the trait is created (or turned off) but it doesn’t get “more intense” in generations or evolve. Or maybe I kind of don’t get it. Well, I don’t think anyone ever said it was an *easy* subject. More chewing.

    Take my first example. Offspring of mice who have been shocked fear the scent of orange blossoms. So, if I understand this right, by shocking the mice parents whenever they smelled the blossom this caused some “stable and heritable” binding or somesuch (I’m really bad at this…) associated with the strand of the DNA the recognizes smells. This physical binding gets passed in the sperm to the offspring and the offspring fear the orange blossom. But this isn’t Lamarckian evolution because, well, it’s not evolution. The mice aren’t changing. It could hypothetically affect natural selection but not directly. Well… sorry if I garbled it.

    Thanks.

    Shit though. This probably makes shyness inheritable. Thanks, mom. *sigh*

  25. says

    The clearest examples of epigenetics are the changes that occur during differentiation. The “only” difference between a brain cell and a liver cell and a fat cell is differential epigenetics. The genome sequence doesn’t change (much, usually, unless there is transposition which there sometimes is), what changes is the epigenetic programming of the genome.

    In terms of the change in the gain in the fear response transmitted via sperm to offspring, it is probably a differential programming that allows for increased expression of receptors for that specific odor. With more receptors, you get more sensitivity odor detection. With more sensitive odor detection in the nose, the “fight or flight” state can be activated more easily.

    If the DNA is modified by methylation so that more copies get transcribed (or more copies of the transcription factor, or fewer copies of the transcription repressor), then the relevant cells have more of that receptor and are more sensitive to whatever the receptor detects.

    Relative sensitivity of cells to different signaling molecules needs to be specified during differentiation. The only reason that some cells are sensitive to estrogen is because they express estrogen receptors (or things that have estrogen receptor activity). Essentially no receptor is perfectly specific, they all of some degree of cross-talk. All that cross-talk translates into more degrees of freedom for physiology to use to control itself with.

    Each cell has to “figure out” how it is going to respond to every substrate it has receptors for. That (mostly) occurs during differentiation, with the relative signaling properties (gain, thresholds, onset time, hysteresis, etc.) determined epigeneticly (and locally for each cell depending on its local environment and needs).

  26. Rich Woods says

    Relative sensitivity of cells to different signaling molecules needs to be specified during differentiation. The only reason that some cells are sensitive to estrogen is because they express estrogen receptors (or things that have estrogen receptor activity). Essentially no receptor is perfectly specific, they all of some degree of cross-talk. All that cross-talk translates into more degrees of freedom for physiology to use to control itself with.

    And just to fuck with peoples’ heads, I’m going to throw in here the possibility that receptor sensitivity also has a quantum mechanical component. But what is new to me is that it could fit in very nicely with the cross-talk idea.

    Shit! Can’t find the reference. Sorry, ignore this for now.

  27. voss says

    Thank you for the timely notice of this epigenetics conference. I subsequently mailed Greater Humanists of Portland a check to attend the conference. Most of my understanding of epigenetics was gained at a lecture here in Portland by Dr. Kent Thornburg of OHSU given for the layperson.

  28. says

    Yeah. I wouldn’t put much faith in “quantum mechanical” effects. Their is really no evidence, so far, to suggest this is even likely, never mind plausible, but, kind of like Lemarckian Epigenics, there are some people doing a lot of questionable speculation about it. And, in fact, the latter is probably closer to be semi-true. There is no reason why a system couldn’t evolve as far back as with single cell organisms, where exposure to a toxin, or some other threat, would make being able to “respond” to such a threat more directly, by, say, generating more anti-toxins, via epigenic changes a positive genetic improvement. In fact, many of those single cell organisms product both toxins, and their anti-toxins, as a necessity, to seek out prey. They need both, due to them otherwise killing themselves with them. So, a sudden increase in population (resulting in more toxins in the environment), or a change in the toxin, or even anti-toxin, genes, which resulted in an imbalance, would require regulation of its counterpart, to retain a balance in the organism. Most multi-cellular animals, and even a lot of single cell ones, no longer produce the toxin/anti-toxin pairing. They have developed other methods, and even those multi-cellular organism that produce them likely only produce the anti-toxin in the specific cells that generate the toxin, or hold it for use. As with all genetic baggage, the toxin/anti-toxin system is unlikely to have just vanished entirely, deleted from the genome. Rather, its got hijacked to other purposes. There are, after all, other threats to multi-cellular animals, like allergens, which can indicate a presence of an actual toxin, in small enough amounts that it can simply be avoided entirely, or in the future.

    And, of course, if it can be hijacked for that purpose, there is no reason why it couldn’t be hijacked for, say, aversion to scents, in the case of mice, or other similar responses, where there is a potential direct benefit to regulating an anti-whatever response, to external stimulus, by using a previously quite different mechanism.

  29. thlaplacedemon says

    woozy @ 26

    Take my first example. Offspring of mice who have been shocked fear the scent of orange blossoms. So, if I understand this right, by shocking the mice parents whenever they smelled the blossom this caused some “stable and heritable” binding or somesuch (I’m really bad at this…) associated with the strand of the DNA the recognizes smells. This physical binding gets passed in the sperm to the offspring and the offspring fear the orange blossom. But this isn’t Lamarckian evolution because, well, it’s not evolution. The mice aren’t changing. It could hypothetically affect natural selection but not directly. Well… sorry if I garbled it.

    This is a bit of a nitpick, but news outlets keep reporting this paper incorrectly and it’s making me crazy. The Kerry Ressler paper (which is totally phenomenal work) does not show inherited fear. It shows inherited sensitivity to a particular odor, as well as a huge increase in the number of olfactory sensory neurons expressing the receptor for that odor (which almost certainly accounts for the behavioral sensitivity.

    It’s still really incredible that odor sensitivity can be inherited epigenetically, but it has a much more straight forward “gene expression->brain->behavior” relationship than conditioned fear would have. (the “behavior->gene expression” mechanism that kicks off the chain is still very mysterious, however.)