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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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May 13, 2013

Another Big Genome Disparity (With Bonus ENCODE Bashing)

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Posted by Derek

I notice that the recent sequencing of the bladderwort plant is being played in the press in an interesting way: as the definitive refutation of the idea that "junk DNA" is functional. That's quite an about-face from the coverage of the ENCODE consortium's take on human DNA, the famous "80% Functional, Death of Junk DNA Idea" headlines. A casual observer, if there are casual observers of this sort of thing, might come away just a bit confused.

Both types of headlines are overblown, but I think that one set is more overblown than the other. The minimalist bladderwort genome (8.2 x 107 base pairs) is only about half the size of Arabidopsis thaliana, which rose to fame as a model organism in plant molecular biology partly because of its tiny genome. By contrast, humans (who make up so much of my readership), have about 3 x 109 base pairs, almost 40 times as many as the bladderwort. (I stole that line from G. K. Chesterton, by the way; it's from the introduction to The Napoleon of Notting Hill)

But pine trees have eight times as many base pairs as we do, so it's not a plant-versus-animal thing. And as Ed Yong points out in this excellent post on the new work, the Japanese canopy plant comes in at 1.5 x 1011 base pairs, fifty times the size of the human genome and two thousand times the size of the bladderwort. This is the same problem as the marbled lungfish versus pufferfish one that I wrote about here, and it's not a new problem at all. People have been wondering about genome sizes ever since they were able to estimate the size of genomes, because it became clear very quickly that they varied hugely and according to patterns that often make little sense to us.

That's why the ENCODE hype met (and continues to meet) with such a savage reception. It did nothing to address this issue, and seemed, in fact, to pretend that it wasn't an issue at all. Function, function, everywhere you look, and if that means that you just have to accept that the Japanese canopy plant needs the most wildly complex functional DNA architecture in the living world, well, isn't Nature just weird that way?

Comments (18) + TrackBacks (0) | Category: Biological News


COMMENTS

1. Tuck on May 13, 2013 9:25 AM writes...

"And as Ed Yong points out in this excellent post on the new work, the Japanese canopy plant comes in at 1.5 x 1011 base pairs, fifty times the size of the human genome and two thousand times the size of the canopy plant."

I think you meant: "And as Ed Yong points out in this excellent post on the new work, the Japanese canopy plant comes in at 1.5 x 1011 base pairs, fifty times the size of the human genome and two thousand times the size of the bladderwort."

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2. Tim McDaniel on May 13, 2013 9:29 AM writes...

I'm sorry to have nothing more substantive than to point to a typo: "the Japanese canopy plant ... two thousand times the size of the canopy plant" should be "... two thousand times the size of the bladderwort".

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3. Derek Lowe on May 13, 2013 9:32 AM writes...

Fixed that one; the bladderworts and canopy plants are now back in their proper places!

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4. John Wayne on May 13, 2013 9:38 AM writes...

And I, for one, welcome our new Japanese Canopy Plant Overlords. I'd like to remind them - as a trusted scientist, I can be helpful in rounding up others to toil in their underground fertilizer caves.

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5. Puff the Mutant Dragon on May 13, 2013 9:53 AM writes...

You read GK Chesterton?

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6. Derek Lowe on May 13, 2013 10:04 AM writes...

#5 -

Some of him - there's so much, that I wonder if anyone's read it all. I very much enjoy "The Man Who Was Thursday", and reading it to my children when they were a bit younger was a great experience - just seeing their expressions at the plot twists. Not being religious, I haven't made time for "Orthodoxy" yet, but Chesterton's prose style is weirdly vigorous enough to make anything worth a look.

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7. Michael Gainer on May 13, 2013 10:35 AM writes...

Speaking as a professional software engineer, I can entirely believe an order-of-magnitude difference in base pair count representing a functionally equivalent level of different species' abilities to address the world in which they find themselves.

As soon as a software project is released, it tends to be turned over to maintenance programmers. Changes are added and bugs are fixed. No single change ever merits a complete rewrite, but as changes accumulate, the structure becomes ever more rococo. If this sequence is permitted to go on indefinitely, at some point it becomes entirely uneconomical to ever do more than adding small fixes upon hacks upon kludges, rather than ever addressing any fundamental concerns. The product has become so convoluted and incomprehensible that a ground-up rewrite is more efficient than any incremental fix. In particular, it's always simpler to add a hack to fix the _effects_ of some other misfeature than it is to remove the (mis)feature and its beneficial effects.

However, before this tipping point is reached, a suitably aware and mature organization can decide to invest in the occasional refactoring. This regularizes the logic, storage, etc. so that subsequent changes are more possible and tend to be simpler.

Translating this to organisms: If a species has been exposed to a frequently changing set of challenges, that set of challenges has never exerted any explicit pressure on the size of the genome, and each cascade of accumulated hacks still retains at least some trivial benefit, (equivalent in function but not base pair count to a more-elegantly expressed representation) I can easily believe that an order-of-magnitude difference could exist in the genome.

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8. LittleGreenPills on May 13, 2013 10:53 AM writes...

Plants unlike most other organisms often benefit from being polyploid. I wonder has that been taken into account in those numbers?

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9. Spaced Needle on May 13, 2013 11:16 AM writes...

My yoga instructor just quoted GK Chesterton yesterday. Weird how that happens--never remember hearing the name before. BTWz-yoga is recommended for chemists, and other humans.

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10. Andy on May 13, 2013 11:23 AM writes...

In Arabidopsis we already see examples where regulatory elements for one gene are found inside the coding region of a different nearby gene. Sequencing the bladderwort genome and using gene prediction software helps us find the stuff we know about (mostly genes). However, it tells us very little about regulation via splice variants, regulatory RNAs (long noncoding, micro, small interfering, etc.) and anti-sense transcription.

Is it more likely that these regulatory processes aren't happening in bladderwort, or is it that we aren't currently appreciating (or even comprehending) the regulation that IS happening? I don't have an answer, but it's exciting to see all the new research in these areas.

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11. a. nonymaus on May 13, 2013 11:41 AM writes...

Re: 10

What is is about Arabidopsis that makes such fancy footwork worth the candle? It seems like that saves a few base pairs but ensures that a single mutation will break multiple genes. And, why doesn't the canopy plant do the same thing with its genes?

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12. Curt F. on May 13, 2013 12:12 PM writes...

Doesn't the function of something depend on what scale, or *for whom* - you are analyzing the function? At the scale of human individuals, junk DNA may just be junk. But at the scale of single nucleotides, anyy nucleotide that free-rides on a self-reproducing system in a way that gets itself copied could be said to be "functional" in a certain sense.

Why is it that molecular biologists are preoccupied with the idea of "junk" DNA but you don't hear ecologists talking about "junk" species, or physiologists talking about "junk" organs.

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13. Crimso on May 13, 2013 3:53 PM writes...

I suspect that the wide disparities seen in genome sizes reflect some aspect of genomic structure/function staring us in the face that no one has yet recognized. Someday someone will see it, and it will make sense (if not antisense), and they'll get a Nobel.

To what extent does physical structure of chromatin affect gene expression? I think the answer is "it depends." On what? On factors we don't yet completely understand, or even yet recognize. We know for certain that it does play a role at least some of the time. So some of that "junk" DNA might well encode things such as siRNAs, etc., while other parts have a purely physical structural role.

It could be something as bizarre as the "junk" DNA acting as spacers (structural role) so that certain genes are physically near each other. There would be some obvious usefulness for this in coordinately regulating gene expression.

IIRC, it has been shown in the past that the arrangement of interphase chromatin is nonrandom, and that specific RNA transcripts have been tracked moving through specific channels in the chromatin to take a nonrandom path to get out of the nucleus.

I could go on, because this sort of idle speculation is a lot of fun. But I've taken enough space.

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14. Crimso on May 13, 2013 4:01 PM writes...

Also worth noting that this phenomenon appears to be more pronounced in eukaryotes vs. prokaryotes. There's bound to be an important clue in that somewhere.

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15. Heteromeles on May 13, 2013 5:43 PM writes...

My first guess is that the Paris genome size represents the result of some sort of parasite, like a viroid or a transposon. It may also represent ancient hybridization.

Here's the thing about Paris: it's a close relative of Trillium, and so far as I know, it has the same lifestyle. It's genome is about 15% larger (http://www.sciencedaily.com/releases/2010/10/101007120641.htm), although both of them have enormous genomes. Neither of these plants are enormously adaptable (e.g. they don't grow in water and in air, nor do they have wide ecological ranges or numbers of alternative forms) so the possible functions for that huge genome might have to do with producing weird toxins, supporting a lot of symbionts, or similar. So far as I know, none of these apply to Trillium or Paris. There's nothing known to be special about them, with two exceptions.

Trillium's exception is that it has been the graveyard of cladistics grad students. A friend of mine worked on Trillium cladistics, and suffered horribly before finding out that the state floras didn't even identify the same species the same way in the eastern US. To put it simply, these aren't clean-cut species in this group, at least on the genetic level.

As for Paris, it's bizarre for a monocot: eight petals and eight leaves? Most monocots work on a three-fold symmetry (that's where Trillium gets it's name, after all), and breaking that symmetry suggests there's something weird going on with Paris' structural genes.

Looking at all this, I tend to suspect that there's simply a lot of noise masquerading as DNA in their genomes. What caused it is the interesting question. It would be truly interesting if most of the diversity in Trillium and Paris genes turned out to be viroids. Or, possibly, it's lolcat jpegs. Whichever, I'm skeptical about it being functional.

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16. sparc on May 13, 2013 11:18 PM writes...

It should be noted that intelligent design creationists, especially Wolf-Ekkehard Lönnig, characterized Utricularia's traps as a hallmark of irreducible complex structures that could not have evolved. At the same time they claim that there is no such thing as junk DNA because any piece of DNA has some function. Thus, it is quite ironic that a species from this genus lives with only tiny amounts of junk DNA.

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17. Morten G on May 14, 2013 4:19 AM writes...

Read Koonin E. V. (2011). Logic of Chance, The: The Nature and Origin of Biological Evolution. It's an excellent book and addresses many of the questions you guys have about junk DNA, prokaryotes vs eukaryotes etc.
Here's a review: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400892/

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18. Sili on May 17, 2013 1:02 PM writes...

I started reading The Napoleon of Notting Hill (didn't remember the quote, though), but never managed to slug my way very far through it. Is it worth picking up again?

I used to enjoy the Father Brown works, but I wonder if I'd like them today.

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