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Rationally Speaking is a blog maintained by Prof. Massimo Pigliucci, a philosopher at the City University of New York. The blog reflects the Enlightenment figure Marquis de Condorcet's idea of what a public intellectual (yes, we know, that's such a bad word) ought to be: someone who devotes himself to "the tracking down of prejudices in the hiding places where priests, the schools, the government, and all long-established institutions had gathered and protected them." You're welcome. Please notice that the contents of this blog can be reprinted under the standard Creative Commons license.

Wednesday, April 01, 2009

Epigenetic what?

The other day I posted on my FaceBook profile that I better hurry up to finish my presentation on epigenetic inheritance. One of my friends commented: “I have no idea what that means, but good luck to you!” Ironically, that is, in part, the point of my presentation: understanding what it all means. Let me explain.

I am in Durham, NC, at the National Center for Evolutionary Synthesis, where — together with two former postdocs of mine — Christina Richards (soon at the University of South Florida) and Oliver Bossdorf (now at the University of Bern), I am running a brainstorming workshop on the meaning and potential importance of epigenetic inheritance.

Epigenetics is an old word, which traces back to Aristotle, and has a long and convoluted history in biology. Today it refers to a panoply of molecular phenomena ranging from methylation patterns of DNA sequences to prions, from so-called “interference RNA” to the tridimensional arrangement in the cell nucleus of a particular class of proteins called histones, which closely bond to and stabilize DNA. What all these things have in common is that in one way or the other they help direct the development of living organisms, turning certain genes on or off in particular cell lineages, and responding to signals from the external environment. The “epi-” in epigenetics stands for a general class of phenomena “beyond” the genes.

But why, you may ask, is an evolutionary biologist interested in epigenetics? Because a subset of epigenetic effects turns out to be heritable across generations. This means that there is something else other than classical genes (i.e., sequences of DNA) that both carries information and is passed from one generation to the next. This is big news for biologists (though the suspicion had been around for a while), because it suddenly broadens and complicates — possibly dramatically — our concept of inheritance, with a wide range of consequences for how we understand evolution. After all, the natural variation among organisms so crucial for natural selection to work had been assumed until recently to originate only from changes in gene sequences. Depending on how much epigenetic inheritance there turns out to be in the living world, the job of biologists will become much more complicated and interesting at the same time (biologists, by nature, like messy stuff, unlike, say, physicists, who always look for simple solutions to simple questions — oh boy, am I going to get in trouble for this one!).

What we are discussing here at Durham, among other things, is precisely how to find out whether epigenetic inheritance is a negligible curiosity or a widespread phenomenon and, if the latter, what consequences it might have for the way we look at evolution, genetics and development. The consensus answer that is already emerging (both from this workshop and from the recent literature) is that epigenetic inheritance as a whole is no fluke, but that different types of heritable epigenetic effects range all the way from very rare (e.g., structural inheritance of cell-surface properties, probably confined to some unicellular organisms) to ubiquitous (e.g., DNA methylation and RNA interference), with others being common in some groups of organisms but absent or rare in others (e.g., a phenomenon called “paramutation,” found in some species of plants).

Skeptics of epigenetic inheritance (of which there are a good number among professional biologists) point out that the empirical evidence is scarce and that the very concept of epigenesis is rather fuzzy. The first objection is becoming less and less tenable. One of the participants to our workshop, Eva Jablonka of Tel-Aviv University, has a huge review paper in press in the Quarterly Review of Biology, in which she details hundreds of known and published examples; and if some of the talks I’ve heard here so far are any indication, there will be much more hard data coming out soon.

As for conceptual fuzziness, my response during the introductory talk I gave at the workshop is that — contrary to what most biologists would acknowledge — the concept of gene itself is not exactly crystal clear either. This is not because geneticists don’t know what they are talking about, but because there are several legitimate uses of the word “gene” that can be deployed in different contexts, depending on one’s research agenda. And some of these uses are not entirely compatible either, and certainly not equivalent to each other.

Consider, for instance, the fact that some biologists refer to genes as whatever has causal effects on the formation of phenotypes and happens to be heritable. Well, by that definition both classical DNA-based “genes” and a variety of epigenetic phenomena qualify! In other cases, genes are defined simply as sequences of DNA that code for a particular protein. That not only excludes epigenetic effects, but also large swaths of DNA sequences that regulate development even though they do not produce proteins. You see what I mean?

Epigenetics is at the threshold of becoming an established discipline in the biological sciences, with implications for genetics, developmental biology, evolution and even medicine (many epigenetic effects are causally involved in a variety of diseases). P.B. and J.S. Medawar, in their classic Aristotle to Zoos (1983) famously said that “genetics proposes, epigenetics disposes,” meaning that the whole of epigenetic processes is what allows genes to produce phenotypes. If that is the case, and I don’t see any good reason to doubt it, epigenetics is poised to become a central discipline in 21st century biology.

20 comments:

  1. "This means that there is something else other than classical genes (i.e., sequences of DNA) that both carries information and is passed from one generation to the next."

    I absolutely believe this.

    My German Catholic grandmother on my mothers side and I share most of the same interests or hobbies tho I never was raised near her and had no idea what she liked or was doing all my growing up years. Rose growing, bread making, painting (tho I don't paint anymore). She's also been a really good golfer...I'm not such a great golfer, but all the rest of her interests I share with her just as if I had been raised right next door to her.

    Very peculiar if you ask me. And if it's not genetic,

    (Maybe our body structure (type) and brain shape or size leads us to certain interests and pursuits?)

    ..then it must be "Supernatural". :)

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  2. The concept of species is not exactly crystal clear either. Biological systems usually refuse to fit neatly into our definitions and categories. That's part of why biology is so interesting. :)

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  3. Awesome. It is always nice to see things getting shaken up a bit in any field. Stuff like this keeps a subject exiting and progressive. When the LHC comes online, let's hope they find exactly what they don't expect!

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  4. Well, by that definition both classical DNA-based “genes” and a variety of epigenetic phenomena qualify! In other cases, genes are defined simply as sequences of DNA that code for a particular protein. That not only excludes epigenetic effects, but also large swaths of DNA sequences that regulate development even though they do not produce proteins. You see what I mean?

    Actually, I don't think there is a valid point about there. The confusing part is only that we call it "genetic" inheritance. What we really mean is of course "genomic." There is a mechanism for direct inheritance of genomic material, and genes and other stuff of DNA is embedded within that material. Things inherited in other ways could then be termed "epigenetic."

    Does that make sense?

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  5. My German Catholic grandmother on my mothers side and I share most of the same interests or hobbies tho I never was raised near her and had no idea what she liked or was doing all my growing up years. Rose growing, bread making, painting (tho I don't paint anymore). She's also been a really good golfer...I'm not such a great golfer, but all the rest of her interests I share with her just as if I had been raised right next door to her.

    Very peculiar if you ask me. And if it's not genetic,

    ..then it must be "Supernatural". :)


    Sorry, but this is all hogwash. You make no argument that - if we accept the premise that those shared traits are inherited - it needs to be anything but normal genetic inheritance.

    Also, you seem to equate non-genetic inheritance with "supernatural." How did you arrive at that? Epigenetics is supernatural now?

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  6. [I]t needs to be anything but normal genetic inheritance.

    So, say, my math ability and drawing talent are classified as normal genetic inheritance? Does this mean it’s possible to see if a person has a certain talent by examining his DNA sequence? I do find this interesting. Hey, I might have other untapped abilities. :)

    This also implies that there is non-normal genetic inheritance. Maybe someone can educate me by giving examples. If my questions are too basic or tedious, please provide me a link that I can read upon. Thanks.

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  7. "Also, you seem to equate non-genetic inheritance with "supernatural." How did you arrive at that? Epigenetics is supernatural now?" Putting supernatural in quotes and adding a smiley implies a joke. A sense of humor isn't a bad thing to have, along with a knowledge of biology.

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  8. "....epigenetics is poised to become a central discipline in 21st century biology"

    Sir C.H. Waddintong is happy now!, :)

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  9. Catana, sorry, I did not see that "supernatural" was a joke. Just sounds like woo to me.

    z.wu:
    So, say, my math ability and drawing talent are classified as normal genetic inheritance?

    First, are we sure those traits are inherited at all? And if they are, then we must at present start by showing why it would be epigenetic, rather than genetic.

    This also implies that there is non-normal genetic inheritance.

    Pfft! No, I don't mean to imply that. I meant "normal" inheritance, the genetic way.

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  10. yes, epigenetic inheritance is miraculous....otherwise, someone please explain to me how it happens and why: how is it that an organism somehow emerges out of the womb with the right, adaptive trait at the right time?

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  11. Bjorn,

    I'm not sure that your proposed solution quite works. We could, I suppose, *define* genomic inheritance as the inheritance of just the DNA nucleotide sequences -- so leave off all the methylation, the chromatin condensation form, etc., but that wouldn't correspond to most usages of "genetic inheritance..."

    The lack of clarity doesn't emerge from the *impossibility* of coming up with a definition, but the fact that there is no one definition that captures most of what's in use...

    jk

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  12. BTW: I'm in Providence, RI, to participate in a panel at Brown (Massimo - IIRC you spoke at an earlier session of this series) with the title "What's New in Evolution." I'll be talking about the roles of commensal bacteria in multicellular eukaryotic evolution...

    One interesting thing of course is that we acquire (some of) our e.g. our gut microbiota from our mothers during birth, some of it from our mothers during nursing, some of it from family / group members we live with as we grow up, and some of it from the world at large, and then pass parts of the inherited & acquired set onto our offspring (and other group members, etc.)... So it's another form of inheritance, along with the other epigenetic modes and niche construction, etc....

    (BTW: I'm betting we'll discover that membrane templating is more variable and that the variations are more important than is currently thought, but I haven't got any particularly good evidence... Just a hunch...)

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  13. thought you may find my paper interesting on a new macroevo hypothesis involving epigenetics, the maximum genetic diversity (MGD) hypothesis.

    Inverse relationship between genetic diversity and epigenetic complexity
    http://precedings.nature.com/documents/1751/version/2

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  14. I do not have a background in biology but excel in other fields. All of this discussion about Epigenetics seems related to evolution and survival theory. So let's start simplifying this. If genes change, it's due to the environment from what we eat, what we experience (climate, people, activities) etc..
    Our human bodies are known to change and this change gets past down to the next generation. It is not a coincidence that people under the same lineage will have the same traits and interests. For example people with the genetic code for having slender hands and long thin fingers will naturally tend to have white collar jobs and do less labour intensive work. Or maybe a history of piano players in the family. Already you can see how the size of your hands affects your disposition in life. How about people with the genetic code of having an affinity for drinking alcohol. Would those people have the same interests as their grandparents such as sports or other social events where alcohol was a major factor?

    What do you think about this doctor?

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  15. Pers raises an interesting point regarding the recreation of environmental influences on phenotype over time...

    One possible explanation for while identical twins tend to have more personality traits in common than non-identical twins is that identical twins *look the same* and are therefore *treated more similarly* than non-identical twins. We know from years of social science research that our physical appearances matter to how others treat us, so people that look more similar will tend to evoke more similar responses in others, and this in turn will tend to shape their personalities, views of the world, etc.

    Now of course, individual genes *don't* change in guided ways from our interactions with the environment. Genetic mutations occur "at random" due to environmental stressors. Some epigenetic changes might occur adaptively in response to environmental change, but even that isn't the norm.

    But the interaction of things we do have (more) control over (jobs, activities, etc.) and the things we don't have (as much) control over (body-type, etc) can result in traits being reliably inherited that are not in any way genetic -- they are social. As pers notes, if my family has a particularly spindly average phenotype, and has traditionally engaged in work requiring fine-motor skills but not strength, and I'm born with the same basic phenotype (which is, presumably, heritable in the "normal" way) the chances are good that for practical and social reasons I'll follow in the family business and not try to become a ditch-digger or line-backer (to mix time-periods).

    jk

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  16. Science is the greatest "revealer" of mystery. Epigenetic inheritance or effects is a good example of a new mystery revealed through scientific inquiry.

    When we try to explain phenomenon we, quite naturally, reduce the phenomenon to explanatory terms. These cannot be mysterious. The act of explaining things is sort of like taking a digital .jpg image. We compress the totality of data to a manageable and portable image. The story of genetic inheritance is an example of this. The simple notion of genetic inheritance is that genes are responsible for inherited traits and by studying genes we will discover where traits genetically "reside" and that knowledge will be powerful and useful.

    This simple, albeit useful, explanation disposes of a lot of real data that is now being scooped up by "epigenetic" thinking. And why shouldn't it be that way - there is nowhere in the real world where reproduction is 100% true - there are always changes. Even clones are different from each other. So how do we explain that variation? There must be other influences and these unknown, mysterious influences are probably centrally important to explaining mutation. Afterall, without mutation we would perish.

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  17. http://www.scienceblog.com/cms/new-nucleotide-could-revolutionize-epigenetics-20334.html

    some new interesting developments!

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  18. Biological structural shapes and biological strategies are interdependent. Perhaps the ability to inherit a change in a biological form is one way, or part of the way, that an adaptive trait can be made heritable.

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  19. Massimo is incorrect in stating that the word "epigenetics" originated with Aristotle. Aristotle may have used the word "epigenesis", but it has a completely different meaning. Conrad H. Waddington is the first human being to use the word "epigenetics" in its current definition.

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  20. Dick,

    you read my sentence incorrectly. I said that the word originated with Aristotle, which is correct as far as I know. But I also said that it has a long and convoluted history, during which it has changed meaning several times. Waddington's meaning, incidentally, is the first one in modern times, but not the one most currently accepted.

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