Almost half of the human genome is made up of transposable elements (TEs). I’ve always been fascinated (and amazed) by this fact, partly because it seems dangerous and messy. This is because it IS dangerous and messy: TEs are essentially all viruses, capable in principle of being reanimated to do what they love to do, which is invade other parts of a genome. When they do this, they can (and do) cause damaging mutations. That’s one way they can blow up a perfectly good cell or embryo; another way is to destabilize the genome through their interactions with other TEs (numbering, let’s remember, in the millions). And so, multiple molecular systems are devoted to suppressing the activity of these parasites. (This must be annoying to the intelligent designers who wove the genomes together, but that’s a topic for the “Argument Clinic.”)
But wait, there’s another way that a retroelement (fancy word for a retrovirus-like parasite in a genome) can cause suffering and chaos, just reported this month in Nature Genetics. Paper is open access.
Transposable elements (TEs) are scattered across mammalian genomes. Silencing of TEs prevents harmful effects caused by either global activation leading to genome instability or insertional mutations disturbing gene transcription. However, whether the activation of a TE can cause disease without directly affecting gene expression is largely unknown. Here we show that a TE insertion can adopt nearby regulatory activity, resulting in the production of cell-type-specific viral-like particles (VLPs) that affect embryo formation. Failure to silence an LTR retrotransposon inserted upstream of the Fgf8 gene results in their co-expression during mouse development. VLP assembly in the Fgf8-expressing cells of the developing limb triggers apoptotic cell death, resulting in a limb malformation resembling human ectrodactyly. The phenotype can be rescued by mutating the retrotransposon coding sequence, thus preventing its full endogenous retroviral cycle. Our findings illustrate that TE insertions can be incorporated into the local genomic regulatory landscape and that VLP production in post-implantation embryos can cause developmental defects.
The paper shows that a certain TE can get itself expressed (activated) by tagging along with legit genes (a limb-development gene in this case, Fgf8) and then actually make viral particles that then cause massive cell death.
That is interesting, and weird that they can produce virus-like particles. TEs are seemingly benign in most cases, but some do cause harm, while I know a couple that have been recruited into bringing about evolutionary innovations.
Hmm, I’ve long been curious about whether and how often TEs make particles, since so many of them (including the one described in this paper) encode the needed proteins: gag, pol, and env. My guess is that this (generation of particles) is not super rare, but I don’t know. I would not call it weird.
This is true statistically, but not because the elements are inherently benign in my opinion. A TE is a mobile element that exists to invade other parts of the genome. That action can only be benign when the landing site can tolerate the disruption, and recent review articles (e.g. this and this) summarize the ways this can be (as we should predict) bad. I recall that John Avise (in his book about bad design that I reviewed many years ago) surmised that a lot of transpositions are invisible because they occur commonly during early development/gametogenesis and kill the embryo.
My view is that TEs are “benign” because they are targeted by defensive mechanisms that take them out of commission. In fact I would argue that these extensive systems are evidence that evolution doesn’t see them as benign, but rather the opposite.
Although this paper seems normal enough, research in junk DNA like retroviruses often produces hype, with claims that our extraneous DNA could have, or does have, a wide array of unknown and mysterious functions. Sometimes this comes from the authors, and sometimes by university press releases. By coincidence, here is Larry Moran calling out a recent paper about a similar study that includes virus-like particles. The authors are fairly proper about it, but the press release got all out of hand: Sandwalk: Endogenous retrovirus sequences can be transcriptionally active: the reality vs. the hype This issue with junk DNA is very common, and its too bad for a variety of reasons. Scientists need to find channels to communicate their research to the public thru the media, but the media meanwhile wants clicks and eyeballs. Hence the result.
Another great Larry Moran explanation. Thanks for the link and summary.
The Comments section under that article is also of interest to someone like me who suffers from Gaper’s Block. (An ID/Discovery Institute fan couldn’t help but repeat the “Junk DNA has been debunked!” script despite what Moran had just explained. Facepalm.)
“Junk DNA has been debunked!” is one of those “Top Ten Intelligent Design Greatest Hits!” that just won’t die. When the Discovery Institute after all these years still fails to produce any discoveries, nostalgic replays is all they’ve got.
I am not sure what you mean, but I can see that a distinction needed to be made about retroviruses and their DNA (provirus) insertions. Anyway, what I said wasn’t hype.
I know. That was my point. But hey, I’m just someone who published on murine leukemia proviruses 30-35 years ago.
Not only that, but while you did state above that not all are junk, you didn’t do that more recently. That unwarranted lumping is my main point–your terminology was less important.
I wouldn’t say it that strongly, but I’m glad John wrote this and I find it frustrating to see this use (or, frankly, any use) of the phrase “junk DNA” to describe whole families of parasitic DNA elements that have known activities (you can call them “functions,” I guess but that seems unwise to me) and that are categorized by lineage and structure and characteristics, just as free-living viruses are. Because of the actual facts that we have about retroelements, calling them “junk DNA” is an unnecessary vague label that just invites confusion and is a staple of the nonstop dishonesty of apologists who lack integrity.
Also Mark, I don’t think you intended this, but your phrasing suggests a category of things called “junk DNA” that have (or lack) particular features: “research in junk DNA like retroviruses often produces hype, with claims that our extraneous DNA could have, or does have, a wide array of unknown and mysterious functions.” In fact, retroelements have known features that include the thing that they are named after: retrotransposition. My suggestion (or hope) is that we talk about TEs which are extremely interesting and not “junk DNA” which is a phrase used by charlatans.
Sorry? Who are those charlatans? In my experience, it’s a phrase used by evolutionary biologists to refer to the portions of the genome (around 90% in humans) that aren’t functional. That would include most active retroelements, because they have no function relevant to the organism and are not maintained by selection.
To put a sharper point on it, those that aren’t known to be functional. We fully expect to learn in the future that a tiny fraction of them are functional.
In my opinion, a more explictly provisional term would be far clearer.
It’s a phrase beloved of charlatans whose names you know very well. I know that Larry Moran and others are comfortable with the phrase, and it has become more common in the literature than it used to be. I did wonder if I should write something like “a phrase beloved of charlatans” but I incorrectly assumed that people here would know that “used by charlatans” ≠ “used only by charlatans.”
I confess that I have no clue who you are talking about. Could you name a couple? The only charlatans I’m aware of who use the term are those denying that it exists. And it seems to be more common in the literature because of all the publications announcing its death. Would you prefer — urk — “dark matter of the genome”?
I would not agree with that. Rather, it’s those for which we have good evidence of lack of function. Your description is, in fact, the definition preferred by those who deny that junk DNA exists, and the historical record of the term’s meaning is often falsified that way. (Less often than equating “junk” with “non-coding”, but often enough.) For various reasons, we will likely be wrong about a small percentage, both false positives and false negatives, because the evidence isn’t perfect. Notably, sequences that have recently gained or lost function won’t display the correct signatures.
They assert that it “has function.” They love the phrase and make it the basis of fabricated stories about the history of genomics. That’s your last clue.
That’s even stupider IMO, as if we don’t know what this stuff is. We do.
My problem is the phrase “junk DNA,” which to me implies a class of things. Some observations that might explain my annoyance, then I’m done with the discussion:
Coral reefs are just one example of wonderful structures built on corpses. We don’t call the dead coral “junk coral.” We don’t call rotting logs and decaying leaf litter “junk logs” or “junk leaves.” Hermit crabs don’t don “junk shells.”
The proteasome is sometimes called a “garbage disposal” but otherwise I don’t see anyone calling misfolded proteins “junk proteins” or damaged mitochondria “junk organelles.” Instead, oddly, we call them “misfolded proteins” and “damaged mitochondria.”
Aged erythrocytes are removed from circulation by the spleen. We don’t call them “junk erythrocytes.”
For me, there is a difference between saying “nearly all retroelements in the human genome are debris left by parasitic DNA elements” and referring to repeats generally as “junk DNA.” I see a difference between saying “basically all of the TEs in the human genome are useless or worse, kinda like junk” and talking of “junk DNA” as though there is a kind of DNA that can be categorized in that way.
Do I think that mammalian genomes are at least half debris? Call it junk? Yes I do. Do I think the phrase “junk DNA” is helpful? Nope.
Sounds to me that you’re talking about the people who deny that junk DNA exists and who redefine the term (“no known function” and/or “non-coding”) in order to discredit it. Is that what you’re trying to say? But they don’t love the term; they claim it shouldn’t be used. Perhaps if you tossed out a name or two?
Agreed.
But it is a class of things, i.e. those sequences with no function. We could argue about whether active retroposons have functions, but I think that function, in this case, refers to function for the organism, not a selfish function of the sequence. You may disagree. And just because other things without function aren’t called “junk” seems no good reason to kill off the term.
But do you think we should have a general term for useless DNA? If so, what?
My admittedly cynical view, which I’m certain is correct, is that they love the term because it gives them a great tool for pumping out falsehood. It’s a fable about “human exceptionalism” and about “failed predictions” with some “Darwinism” seasoning. Every apologist who has ever written “junk DNA has a function” is grateful for the existence of that phrase. I once wrote extensively about Alu elements in disease, and noted that an entire series (at the “Reasons To Believe” propaganda mill) about them actually avoided any mention of the fact that they are mobile elements. Have you noticed that these apologists seem almost desperate to avoid any mention of what “junk DNA” is actually made of? YMMV but it seems to me that they know that a story of mysterious miscellaneous weird “junk,” dismissed by lazy doctrinaire “Darwinists,” is bread and butter for bullshit consumers, whereas “vast collections of dead parasites, akin to a coral reef” is different. Just my opinion.
I don’t think we need the term, anymore than we need a term for useless and sometimes dangerous misfolded proteins; that was my point in the post. One group suggested “junk DNA” for “horizontal” reference but “spam DNA” for vertical (i.e. historical). That makes good sense to me but I’m sure it won’t (didn’t) catch on. The thing about “junk,” and the focus on “function,” is that it leaves unspoken the origins of the parasitic spam and leaves unexamined the elaborate expensive spectacular systems that animals have deployed against invasive DNA.
But that’s the problem with using the term in public discourse, John. We all know full well that a very small fraction of those sequences will be shown to have function in the future.
Using that term allows dishonest and/or ignorant people to then assert that because someone found a tiny bit of “junk DNA” to be functional, that all “junk DNA” is functional.
That’s not a problem with the term “junk DNA”. It’s just that a few bits we now think are junk will turn out not to be. If a painting previously thought to be a Rembrandt turns out after examination not to be, that doesn’t invalidate the word “Rembrandt” or show that it’s a bad idea to use the word.
Dishonest and/or ignorant people aren’t going to be deterred by changing terminology.