Epigenetics arise!

By Razib Khan | October 6, 2010 2:51 am

methylation[1]-GIFLast week I quipped on twitter that epigenetics had started to become the scientific deus ex machina of our age, a phenomenon which offered the potential for boundless explanatory power. In the past I have felt that sexual selection and random genetic drift have fulfilled the same roles as one-size-fits-all-explanations at the service of all. The critiques of adaptationism have taken hold broadly, but in lieu of that old-standby it seems that people naturally go seeking other theoretical gurus instead of admitting ignorance as to the nature of things.

Like sexual selection and genetic drift, perhaps more so, epigenetics has made the leap from the pages of Science, Nature, and Cell, to the more humane domains. I became very conscious of this when by chance I ran into someone with a past affiliation with the literary journal n + 1, and they asked me about epigenetics when they became aware of my interest in genetics. And today, I notice that the magazine The New Atlantis has an article in its latest issue titled “Getting Over the Code Delusion”. Here’s the blurb on the front page: “Steve Talbott on epigenetics and the demise of DNA as destiny.” Lest you think that The New Atlantist is selling Left-wing Blank Slatism, here’s the summary from Wikipedia:

The New Atlantis, founded in 2003, is a journal about the social and political dimensions of science and technology…Published by the conservative Ethics and Public Policy Center in Washington, D.C., the journal is a quarterly, and consists of serious essays on a variety of science and technology issues as well as a summary of recent events produced by the editors. The journal has earned a reputation as a traditionalist conservative publication…Conservative writers Leon Kass and William Kristol have both been published in its pages. It is edited by technology expert Adam Keiper, having formerly been edited by conservative writer Eric Cohen.

If Mike Lynch and Jerry Coyne have fits over Sean B. Carroll’s love affair with gene regulation at the expense of old fashion sequence variation, I wonder how they’ll view the inflation of epigenetics which is liable to get more out of control before people begin to gain a sense of perspective. I see on Amazon there are already some suspect titles trying to use epigenetics as stepping stones. For example, Happiness Genes: Unlock the Positive Potential Hidden in Your DNA. One of the blurbs:

“Combining recent studies showing the epigenetic effects of changing our beliefs and behaviors with the wisdom of ancient spiritual traditions, Happiness Genes is a wide-ranging survey of the science of happiness. It asks the reader provocative questions, like considering how our behaviors might be affecting the genetic expression of our children. Baird and Nadel show you how to inventory your ‘happiness assets,’ those relationships, possessions and situations that contribute to your happiness, and then treat them like the valuable resource that they are. Wise and practical, the book is peppered with self-reflection exercises, and ends with a 28 day program that guides you in cleaning up everything in your life that stands between you and happiness. To understand the links between what happiness looks like at the molecular level in our cells, the happiness of entire nations, and how you can take lessons from everything in between to raise your own happiness level, this book is an excellent guide.” –Dawson Church, best-selling author of The Genie in Your Genes

Let’s get a quantitative measure as to the rise of epigenetics.


To do so, I wanted to look at the terms epigenetic, sexual selection, and genetic drift. I checked to see how often they appeared in titles of articles between 1999 and 2009 in Google Scholar (I excluded patents). I couldn’t find an easy way to limit years appropriately for general news archives, so I decided to look at Google Blog Search. The main issue here though is that the number of blogs, and Google’s index, has been growing over the whole 2000s. So what matters for the second chart is the relationship between the three terms, not the absolute values. Again, I looked at post titles.

epigen1

epig2

First, no surprise that genetic drift has the least traction. It’s a background dynamic, just an instantiation of sampling variance. In the scientific literature it does look like titles with epigenetics are rising in a linear fashion. In contrast you basically see a uniform distribution for sexual selection. But the the blog title results show something different: sexual selection still beats out epigenetics. Remember not to focus on the steep trendline, that’s probably an artifact of the rise of the science blogosphere and the thoroughness of Google’s index. Is this plausible? Yes. There are 18 hits for epigenetic in The New York Times between 1999 and 2010. There are 43 hits for sexual selection. The values for the print edition of The Economist during that period are 10 and 17.

Why is sexual selection so popular despite the fact that not that much revolutionary is going on in the science? Generally I think anything to do with selection has appeal as an explanation because of a connection to Charles Darwin. Additionally, sexual selection has something to do with sex, and that makes great copy. Articles about sexual selection offer up the opportunity for nice visuals. In contrast epigenetics gives you the chance to illustrate a methyl group.

What about epigenetics and the future? I really hope the science progresses further. Until we know its limits and bounds we won’t hear the end of neo-Lysenkoists on the Left and the Creationists on the Right. That’s not to say that Steve Talbott is either, though I can’t judge as you can’t read his article online. And certainly it is fair to point out the possible implications of epigenetics in terms of how the phenomenon may make us reevaluate the nature of the heritability of traits. But part of the reason is that we are only now beginning to understand the science. On a coarse phenotypic level I’d bet that epigenetics doesn’t overturn everything we know, rather, it will modulate on the margins.

Image Credit: Jen Philpot

CATEGORIZED UNDER: Behavior Genetics, Genetics
MORE ABOUT: Eipgenetics, Genetics
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  • miko

    I am tentatively sympathetic to the attempt to broaden the concept of biological inheritance and the idea of an “extended evolutionary synthesis.” I’m with Dennett on adaptation being the main game in town, but that it should never be assumed–constraints, bottlenecks, drift, and molecular quirks of the ad hoc systems of inheritance are important in shaping evolutionary dynamics. The way the “central dogma” is presented, taught, and used as a cognitive widget is out of date and limiting. But I find the way this trend, and epigenetics in particular, has been played out in the media is utterly ridiculous. It seemed to me to start with Barry Commoner’s piece in Harper’s “Unraveling the DNA Myth.” What was really weird was his tendency to blame biologists as a group for over-selling the central dogma, combined with leftist paranoia about corporations. Who, I wonder, is doing all this research into DNA methylation that’s getting published in Cell? Literary theorists?

    His main target was biotech and agribusiness… I get the point–biology is more complicated than a flow chart, (most) genes are not autonomous agents that can be swapped around like legos. Adam Wilkins wrote a good short piece about this in Bioessays without the hysterics. But to go from that to the current frenzy of “Darwin was Wrong” and similar headlines is just bizarre. More confirmation that shouting is now the default mode of discourse.

  • Katharine

    I think epigenetics hasn’t found its limits yet. It’s a bit like someone who’s discovered ‘WHOA I CAN DO SOMETHING’ and has just started testing how much they can do.

    We need to establish where some of those limits are, particularly the ones that make people say weird crap such as ‘CURE YOUR CANCER BY BEING HAPPY BECAUSE EPIGENETICS SAYS SO LOL’.

  • Katharine

    The way the “central dogma” is presented, taught, and used as a cognitive widget is out of date and limiting. But I find the way this trend, and epigenetics in particular, has been played out in the media is utterly ridiculous. It seemed to me to start with Barry Commoner’s piece in Harper’s “Unraveling the DNA Myth.” What was really weird was his tendency to blame biologists as a group for over-selling the central dogma, combined with leftist paranoia about corporations.

    I hadn’t heard about this. Can you tell me more about the problems you see about how the central dogma is presented, taught, and used?

  • Katharine

    Reading Commoner’s piece (there’s a link at http://www.mindfully.org/GE/GE4/DNA-Myth-CommonerFeb02.htm if anyone wants to read it), he appears to be parroting a lot of things that are total bull:

    “The Precise Duplication of DNA is accomplished by the living cell, not by the DNA molecule alone” – If you know anything about the process of replication and the numerous enzymes involved, you’d know that this is a gross overgeneralization.

    “GENETIC INFORMATION ARISES NOT FROM DNA ALONE BUT THROUGH ITS ESSENTIAL COLLABORATION WITH PROTEIN ENZYMES” – No, it arises initially from DNA. Enzymes, which are also synthesized from DNA, hack up and re-piece together in different ways the mRNA that is transcribed from the DNA until it becomes the strand of mRNA that they translate into a protein.

    This is BASIC.

    “DNA did not create life; life created DNA” – In the strictest sense, we don’t even know whether viruses are strictly life, but as far as I’m aware we think they’re the first thingy in which DNA developed. DNA came after RNA. There is no life without a genetic code of some sort, if that is what he’s referring to, and if that’s what he means, then that is just so wrong I have doubts about this dude’s ability to do science if he can’t even get something that basic right.

    And never have I been very pro-business either, but the dude is freaking out a little more than I think is warranted about GMOs. Yes, the process has been fraught with mistakes, some tragic, but I don’t think the very fact that they were GMOs themselves is responsible so much as perhaps the lack of foresight of the people engineering that specific GMO.

  • Katharine

    leftist paranoia about corporations.

    Really, I’ve found this accusation from the right sort of weird.

    I think most people who are sane realize that corporations bring us a lot of the crud we need.

    At the same time, most people who are sane realize that a not-insignificant number of corporations do things that are flat-out cruel and unethical (Union Carbide and India, Goldman Sachs, BP, the list goes on and on).

    I can speak at least for myself – I don’t want to drive them all out of business, but really, it is staggering to see what some people will do just for an extra buck even if they’re already insanely rich off their arse and can keep their company going very, very easily and accomplish their aims anyway, and I don’t think it’s worth allowing them that extra buck if it drives someone out of their home, gets them sick, kills them, et cetera.

  • omar

    I work in this field and I think its wonderful that its hot, but the media hype is clearly overblown and misleading. My question is this: do you think it is any more overblown and misleading than ALL the other episodes of media hype about new scientific discoveries? Or do you think this one is worse? Were the standards of popular science journalism better in the “good old days”? Are they getting worse or getting better? or staying the same?
    And do you think scientists contribute to the hype by writing that mandatory last sentence in every grant about how this discovery will change the world? (Actually, I dont know how much basic science people exaggerate in their grants because I have not read their grants, but translational research certainly seems to be universally infected with this virus).

  • Katharine

    And do you think scientists contribute to the hype by writing that mandatory last sentence in every grant about how this discovery will change the world? (Actually, I dont know how much basic science people exaggerate in their grants because I have not read their grants, but translational research certainly seems to be universally infected with this virus).

    Like many things, I think the incidence of this, from what I’ve seen among those fellow members of the scientific community who are at places on the road that I will be in anywhere from a few years to a decade or even two or three decades, happens along a gradient.

    There are some in science who vastly overestimate the world-changing probability of their discoveries.

    There are some in science who vastly underestimate the world-changing probability of their discoveries.

    There are some in science who manage to figure out how world-changing their discovery is.

    There are people who fall at all places between all these marks.

    It is very hard sometimes to figure out how many people think what.

    (Honestly, when you said ‘scientists’ as if it were all rather than just a handful, I have to admit it raised my hackles, the same way other instances of this sort of generalization raise my hackles. Especially because you’re generalizing about a group that you’re a part of.)

  • Katharine

    And unfortunately the thing about media hype that I’ve realized is that unfortunately there’s a lot of it that mostly comes down to the fact that they haven’t spent the time studying these things that we have so they don’t really have nearly as much of an understanding, even if an adequate one, of the various ramifications of various discoveries.

  • Katharine

    And I hate the fact that my last posts on this sound painfully trite, but I thought they needed to be said because I thought they were being overlooked.

  • pconroy

    Yes indeed, the new era is going to be all about Gene Expression!

  • miko

    Really, I’ve found this accusation from the right sort of weird.

    This time, it’s coming from a moderately left Democrat (me). I think some academics often treat privatization of any technology or discovery as lame at best and evil at worst. But I think we agree–corporations have systematic problems that make them tend toward rapacity, but actions have to be judged on a case by case basis. I don’t think I’m wrong to generalize that “corporate” is generally an epithet among the left.

    Can you tell me more about the problems you see about how the central dogma is presented, taught, and used?

    In my experience, it is usually taught (or presented in the media or to non-experts) as something like this:
    1. Genes are stretches of DNA that make mRNA which make protein.
    2. Genes specify traits
    3. Variations in genes lead to variation in traits
    4. Selection on traits is de facto selection on alleles.

    All these statements are true as far as the go, but they miss almost everything interesting about cell biology, development, and evolution.

    The main problems I have are:
    1. The DNA–>mRNA–>protein flow diagram. Not that it’s “wrong,” but that it’s the equivalent of maybe F=ma. Not the best example, but it’s something that is roughly right some of the time in a narrow sense, but tells you little that’s interesting about the underlying phenomena. “Gene” has no definition molecular biologists agree on. Genes produce non-coding RNAs, multiple mRNAs and proteins. RNAs modify/regulate RNAs, DNA, and proteins; proteins modify/regulate proteins, RNAs, and DNA. Metabolites modify everything. These aren’t details–they are how cells work. And the fact that the structure of all the other proteins and RNAs is also specified by DNA does not magically restore linearity, because you’ve entered an emergent (sorry) level of organization with its own rules and dynamics. If you only consider digital primary sequence information, then the direction of flow is roughly linear, but that is not the only kind of information cells use or need.

    2. Genes specify traits. OK, kinda. Genes specify primary peptide structure. You could say regulatory elements specify spatiotemporal expression dynamics, but you’d be wandering into a mess–do promoters specify these dynamics or is it the transcription factors (and their promoters and modifiers and upstream regulators) and other genes that act on the promoter? Does it make sense to say any of them control it? All of them? Several orders of organization and causal networks later, genes influence the physiology and behavior of cells, which affects developmental processes, etc, etc. Most genes are involved in the production of many, many traits. So, I’d say genes partially specify the processes that contribute to a broad spectrum of traits. Genes are a poorly organized and partially interpretable parts list, not a blueprint, program, algorithm, or any of the other trendy analogies.

    3. Yes, allelic variation has a large effect on phenotypic variation, but it is not 1-to-1 and it is not linear due to pleiotropy, epistasis, GxE. It’s like saying running affects the outcome of baseball games.

    4. Selection on traits selects allelic combinations to the extent that it can. Multiple competing selection pressures, linkage, meiotic drive, developmental constraints, all add nuances to these processes that have significant impacts on morphological evolution.

  • http://blogs.discovermagazine.com/gnxp Razib Khan

    two points

    – i will be getting a copy of *the new atlantis* article soon

    – i hope epigenetics overturns a lot. that would be fun! and probably practical. i wouldn’t bet on it though. though my skepticism is more a prudent default state than truly informed by wariness of the science as such.

  • Katharine

    I don’t think I’m wrong to generalize that “corporate” is generally an epithet among the left.

    In some segments it is, I’ll agree on that (the more extreme parts certainly use it as an epithet; I’m socially very, very liberal and at the same time I’m economically somewhere from left-of-center to moderate and the low levels of braining going on on both the parts of the wacko far right and the folks who are wacko but vote Democrat are staggering and surprisingly similar in some ways). I’ll admit that corporations evoke strong negative feelings in me precisely because of the numerous times they’ve abused people in the past. It would be nice if I could find more information on the nature of the systematic problems which prompt their rapacity, because it’s hard to tease out any precise causes other than, say, moral deficiencies on the part of various people who run those things.

    The DNA–>mRNA–>protein flow diagram.

    I think the DNA ->mRNA -> protein flow diagram is more of a backbone to what goes on. True, it’s a little scant and doesn’t fully encompass the process, taking into account that many of the molecules that drive the process are themselves RNA and proteins, but the basic DNA -> mRNA -> protein flow is the backbone of the whole process.

    Genes specify traits.

    Really understanding the whole process of how one gets from gene to trait via protein expression is, I agree, pretty complex, and it varies from gene to gene, and genes can effect multiple traits and one trait can be affected by multiple genes (e.g. a mutation in the leptin receptor gene can lead to a person becoming obese, a mutation in one allele on an X chromosome can cause hemophilia, et cetera, and a bazillion genes affect intelligence).

    A lot of this really comes down to ‘shit, why can’t we just make everybody take general biology and a genetics class?’ Which would be nice if it happened, honestly.

  • Katharine

    “Gene” has no definition molecular biologists agree on.

    Not ‘a strip of DNA that gets translated into RNA’?

  • Katharine

    You know what’s funny?

    I see a lot of articles that are ‘O HAY WE FOUND THIS GENE THAT AFFECTS THIS IF YOU MUTATE IT’ and some of them don’t actually say what that gene makes.

  • http://blogs.discovermagazine.com/gnxp Razib Khan

    btw, this post as 2 X the normal level of retweets:

    http://topsy.com/twitter/razibkhan

    and a link from MR.

    again, a testament to the broad appeal of epigenetics?

  • d e

    Talbott is online: http://www.netfuture.org/

  • miko

    Not ‘a strip of DNA that gets translated into RNA’?

    Nope, it turns out a shockingly large (don’t have the number at hand) amount of intergenic DNA is transcribed sometimes, but it’s just (probably) noise.

  • http://blogs.discovermagazine.com/gnxp Razib Khan

    i hate it when i have to blog about molecular biology as a necessity. if you go anything beyond banal it is impossible to not be wrong because of the nature of definitions. that’s why i like linking to things and passing the buck :-)

  • http://www.misaha.com Savva

    Epigenetic control system of the organism doesn’t start at the cellular level. It carries four fundamental programs of life — development, maintenance, reproduction and death,
    The system is hierarchical – whole organism, organs, tissues and cells (the bottom level).

    Limiting epigenetic manifestations by cellular level is a temporary stupidity. The problem is that the physical carrier of the epigenetic control system is yet unknown.

    See my introductory article in our book “LIFE and MIND – in Search of the Physical Basis” 2007 available at http://www.misaha.com – BOOK

    Savely Savva

  • http://www.iSteve.blogspot.com Steve Sailer

    People who write self-help books should combine epigenetics with brain scans: if you do X three times before breakfast every day, this will epigenetically rewire your brain [insert stock photo of brain scan] and you will close more big deals. This books would sell millions in airport bookstores.

  • Katharine

    Nope, it turns out a shockingly large (don’t have the number at hand) amount of intergenic DNA is transcribed sometimes, but it’s just (probably) noise.

    Then why don’t they call the DNA that’s transcribed from a gene?

  • Katharine

    Savva, you are a purveyor of bullsh*t.

  • http://blogs.discovermagazine.com/gnxp Razib Khan

    should i have let that sort of self-promotion through?

  • http://www.farrellmedia.com John Farrell

    Razib, I look forward to your take on Talbott’s article. They’re positively breathless about it over at WWwTW, which always sets off my bullshit detector.

    :)

  • http://blogs.discovermagazine.com/gnxp Razib Khan

    lol. i didn’t know they were into histones and cytology! another permanent thing in need of defense by men of the west! :-)

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  • Chuck

    “What about epigenetics and the future? I really hope the science progresses further. Until we know its limits and bounds we won’t hear the end of neo-Lysenkoists on the Left and the Creationists on the Right.”

    Here was Edith Heard ‘s comment:

    It is amazing to see how epigenetics has been propelled into the headlines over the past decade. On the one hand, it has been hailed as an explanation for inter- and intra-individual diversity, and on the other, as a purveyor of hidden information — beyond genes — that can be influenced by intrinsic and extrinsic fluctuations. The ‘hype’ surrounding epigenetics may partly be due to the fact that, since the human genome was sequenced 10 years ago, we have been confronted with the reality, and perhaps inevitability, of our genetic constitution. Epigenetics may provide hope that we are more than just the sequence of our genes — and that our destiny and that of our children can be shaped, to some extent, by our lifestyle and environment. The recent groundbreaking discoveries on induced pluripotency have also brought the reversible nature of epigenetic states to the forefront. Such reversibility brings much hope for treating diseases such as cancer, which have not just a genetic but also an epigenetic basis, for which ‘epidrugs’ can be used to reverse aberrant epigenetic changes (epimutations).”
    (Heard et al. 2010. Ten years of genetics and genomics: what have we achieved and where are we heading?)

    There clearly is an ideological Lysenkoisian aspect to the promotion of epigenetic.

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  • J Thomas

    “Honestly, when you said ’scientists’ as if it were all rather than just a handful, I have to admit it raised my hackles, the same way other instances of this sort of generalization raise my hackles. Especially because you’re generalizing about a group that you’re a part of.”

    Note that he didn’t exactly make that generalization. He invited YOU to make that generalization and tell him what you thought the group was doing. And you sensibly did not.

  • J Thomas

    “The Precise Duplication of DNA is accomplished by the living cell, not by the DNA molecule alone” – If you know anything about the process of replication and the numerous enzymes involved, you’d know that this is a gross overgeneralization.

    “GENETIC INFORMATION ARISES NOT FROM DNA ALONE BUT THROUGH ITS ESSENTIAL COLLABORATION WITH PROTEIN ENZYMES” – No, it arises initially from DNA. Enzymes, which are also synthesized from DNA, hack up and re-piece together in different ways the mRNA that is transcribed from the DNA until it becomes the strand of mRNA that they translate into a protein.

    Of course, this is a gross generalization.

    The problem is we need a new metaphor. Here’s mine:

    Imagine you have a machine shop, and a big library full of blueprints on microfiche. Some of the blueprints include all the information the machine shop needs to make a microfiche reader.

    The library includes blueprints for most of the tools in the machine shop. And also for various consumer products that the machine shop can produce to exchange for everything else it needs. And the library includes a business plan to tell it what to produce and when.

    This business plan has evolved by repeating whatever has worked well in the past. So the shop makes swim gear in the late spring and skis in the late fall. But how does it know when spring comes? The library can’t tell it. The business plan has evolved to use whatever signals it happened to find useful in the past. So it might tell spring by subtle changes in wood, that it evolved to measure for some other purpose. Or sensors it developed for another purpose might track the difference between the ratio of UV versus red light at noon. Or it could measure temperature patterns. Or even use a clock. Each method has problems. Different parts of the business plan might use different measures to track the seasons.

    There might be multiple business plans, and something signals when to switch from one to another.

    The system has to track lots of things, not just seasons. Like temperature. Some machine parts are affected by temperature, they don’t work correctly when it’s too hot or too cold. The library may have blueprints for variations that work right then. And a temperature shift can signal which version to make. How does the system measure temperature to decide which parts of the library to read? There are lots of ways and different processes will vary. One way is to design particular machine parts which are particularly sensitive to temperature, which provide the signal by their failure.

    And if you get an unusual sequence of events, that call forth an unusual collection of machine parts that are not usually all present at once, anything can happen. Because there has been little natural selection to prepare for that rare circumstance.

    It’s possible to look at this and say “The library is in control because every machine part has its blueprint in the library.”. That’s true in a way.

    Or you could say “The library is in control because every scrap of the business plan gets copied out and read to decide what to do next.”. That’s also true in a way.

    Or you could say “The library is in control because there are parts of it that determine which other parts can be read, by themselves getting changed, even though they don’t actually produce anything themselves.” And that can be sort of true too.

    All that was useful when it was becoming known. But nowadays it kind of misses the point. Now the point is, we have lots of feedback loops that were evolved by whatever accidental controls happened to work at the time.

    And if there’s any immediate practical result from this, it’s that — to the extent you want your body to work as it was evolved to — you should try to live in an environment that provides the same cures that your ancestors got from the environments they lived in.

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This blog is about evolution, genetics, genomics and their interstices. Please beware that comments are aggressively moderated. Uncivil or churlish comments will likely get you banned immediately, so make any contribution count!

About Razib Khan

I have degrees in biology and biochemistry, a passion for genetics, history, and philosophy, and shrimp is my favorite food. In relation to nationality I'm a American Northwesterner, in politics I'm a reactionary, and as for religion I have none (I'm an atheist). If you want to know more, see the links at http://www.razib.com

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