National Geographic

Why I Keep Harping on the Dynamic Genome

This week one of my readers, Lauren, suggested that epigenetics is a leftist plot:

The entire concept of epigenetics is being highjacked today for the Left’s eternal propaganda of neo-Lysenkoism — that “Nurture over Nature”, environment and not heredity, is what most significantly determines human qualities.

It’s essential to understand that the “methylome” is NOT — as the Left would like to give us the impression — an alternate kind of biological code created by the environment. It is not a competing genome that can overrule inherited DNA. It’s only a part of the chemical apparatus produced BY the DNA, to operate the cell.

I wouldn’t bother giving Lauren any attention except that her comment really gets under my skin. I never said or implied that environmental influences determine human qualities, for one thing. But worse than that, implicit in her remark is the opposite claim, which is just as insidious and, unfortunately, much more commonly argued: that genes determine our fate, that the genome is fixed, that environments don’t matter.

I’ve ranted before about the perils of genetic determinism and how it has contributed to an overblown fear of all things genetic. Where does the idea come from? And why does it have such a stronghold on our culture? Should I blame social Darwinism? Nazis? Gattaca? Or maybe it starts in biology class.

I’d guess that the vast majority of people, if they think about the genome at all, think of it as a static, abstract code, a string of letters that you’re born with and can’t do anything about. That’s sort of true, but sort of not true, and this complexity is something I tend to harp on in blog posts.

The super-long DNA ‘code’ is a physical molecule. It wraps around itself in a certain way so that it can fit into each of our cells. That wrapping affects which genes are turned on and made into proteins and which stay silent. DNA is littered with methyl groups, and these, too, turn genes on and off. And yes, Lauren, methylation itself is genetically encoded, leading to distinct ‘methylation landscapes’ in different tissues. But methylation is also influenced by environmental exposures, diet, and age.

Even if you put those epigenetic influences aside, the underlying genome isn’t fixed. DNA mutations frequently crop up during cell division, making the daughter cell and all of its progeny genetically distinct.

And then there are jumping genes, the subject of a cool neuroscience paper that came out yesterday in Science. Nearly 45 percent of the human genome is made of transposons, or pieces of DNA that can ‘jump’ randomly around the genome. Sometimes jumping genes use a cut-and-paste approach, other times a copy-and-paste, and these insertions can cause coding disruptions that can contribute to disease.

The new study shows that transposon activity is quite variable from one cell type to another. Analyzing the brains of adult fruit flies, the researchers showed that jumping genes are particularly active in ‘alpha-beta neurons’, which are important for processing smell-related memories. Many of these jumping DNA pieces insert themselves near or inside of active genes, likely affecting their function. These “disruptive insertions,” the researchers speculate, could accumulate throughout life, ultimately contributing to memory decline (or, if you’re into hyperbole, to fly “personalities“).

So why am I so obsessed with the dynamic genome? Mostly because it’s fascinating stuff. But I also wish that more people appreciated the unbelievable complexity of DNA and its dances with an ever-changing environment. If you think of the genome as moving and flexible, then it’s hard to fall into the trap of genetic determinism. Isn’t it?

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Photo by Jorge Fardels, via Flickr

There are 16 Comments. Add Yours.

  1. Harald Illig
    April 5, 2013

    Epigenetics Is also being hijacked by the pseudoscientific feel good faith healing herbal ex-hippie crowd, FYI.

  2. Renee Marie Jones
    April 5, 2013

    Some people, I think, have a need for everything to have a single, constant, final answer. I do not know how to get them to understand that sometimes the answer is a littlr more complex, and subject to revision. Thanks for trying.

  3. Michael Nova MD PH.D
    April 5, 2013

    On point Virginia…nice.

  4. philipp
    April 6, 2013

    Great reaction on a user comment …

  5. Steve Moss
    April 7, 2013

    You’re right on a lot of these things, but, you forget to include that the majority of these changes are somatic and not germ line. Only changes to the germ line can be propagated through the generations.

  6. Virginia Hughes
    April 7, 2013

    Steve, thanks for your comment but I don’t see how it’s relevant. Whether the changes are somatic or not, an individual’s genome isn’t static.

  7. Steve Moss
    April 7, 2013

    Hi Virginia, and thanks for the swift reply.

    Perhaps its not immediately relevant when focusing on an individual, but “the genome”, of course, is inherited throughout the generations, but with far fewer changes than are experienced by the many trillions of somatic cells throughout ones lifetime.

    The genome is of course dynamic, and under a variety of influences, but those which don’t impact on the germ line are almost irrelevant when it comes to longer term human evolution.

  8. Steve Moss
    April 7, 2013

    I hope I don’t make it sound like I’m contradicting you, I’m just trying to add an extra point to ponder. My research focuses on the differences within and between genomes over time, particularly on duplications, introns and repetitive/mobile elements :-)

  9. Virginia Hughes
    April 7, 2013

    Not at all, Steve — I appreciate the addition!

  10. Ralph Dratman
    April 8, 2013

    If genes are jumping in the germ line (even occasionally), wouldn’t that cause a problem with alignment? I thought corresponding genes were supposed to line up with each other across homologous chromosomes — or do I have that wrong?

    • Virginia Hughes
      April 9, 2013

      Yes, I believe you’ve got that right. I’ve read that jumping genes in the germline can be particularly harmful, for exactly that reason. On the other hand, they’re pretty small, so I’m not sure that one would necessarily throw off alignment. I’m going to try to round up an actual expert to answer this– stay tuned!

      • Steve Moss
        April 9, 2013

        The literature on this identifies approximately 45% of the human genome to be transposable elements. This is a considerable sum.

        I would argue that more, smaller transposable elements are actually more harmful than fewer larger ones, not least because the probability of non-homologous recombination occurring between duplicate members of transposon families, which should have high sequence similarity would thus increase?

        Though the number and size of transposable elements is formidable, the coding portion of the genome is only around 2%, with a remaining functional portion of around an additional 8%. That’s, of course, a 1 in 10 chance of a transposable element hitting an area that could negatively affect reproductive and/or developmental ability. However, not all mutations, as we know, are fatal or result in a disease phenotype, so measuring the true impact of this is difficult.

        Look forward to a more in depth post on this from someone more versed in developmental and reproductive genetics.

  11. Ralph Dratman
    April 8, 2013

    I forgot to mention: the idea that epigenetics is a left-wing plot sounds wildly implausible to me. How would it happen? I don’t think many biologists would stake their careers and reputations on supposedly scientific conclusions which are actually driven by political ideology. That would be professional suicide, seems to me.

  12. Josh Dubnau
    April 9, 2013

    This is a fascinating study that follows nicely on similar work in rodents, and even human brains. These selfish genetic elements are clearly causing genetic changes in somatic tissue. It seems very likely that the genomes contained within individual neurons of the same brain have different DNA sequences! The big question is, what is the functional impact of this. There are three possibilities: First, it could be inconsequential. Second, it could provide some important variability that the brain utilizes in a way that we do not yet understand. Third, this could be an un-intended consequence of the means by which neurons regulate gene expression. In this third view, transposons occasionally “slip through the cracks” in the defense systems that we have evolved. This might have long-term detrimental consequences to neurons if the effects accumulate over age (http://www.nature.com/neuro/journal/vaop/ncurrent/full/nn.3368.html).

    And obviously, the second two possibilities are not mutually exclusive!

  13. Nikos Parisis
    April 12, 2013

    i wonder what would Lauren think if you talked to her about post-translational modifications??

  14. marina
    May 19, 2013

    Psychologists are the worst. Lack of biological knowledge + eager to be a biological science make this deterministic nonsense.

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