Sunday, March 22, 2015

On the handedness of DNA

Double-stranded DNA forms a helical structure where the two strands are twisted into a helical shape. If you think of the base pairs forming a ladder then imagine that the entire ladder could be distorted by rotating the ends relative to each other. The result would be the helical shape of DNA. The twisting results mainly from the attraction between the planar base pairs (rungs of the ladder.) They are "happier" when they are stacked close together right on top of each other. (The "force" is called "stacking interactions.")

This is not how DNA is actually built since there's never a time inside the cell when the DNA forms a ladder-like structure that's not helical, but you get the picture. [The Three-Dimensional Structure of DNA]

The final form of double-stranded DNA on the right is a cartoon used to illustrate certain features. I've deliberately drawn it with about 10-11 base pairs per turn so you can see the shape of the helix.

Now, imagine that you twisted the ladder in the opposite directions to those shown in the figure above. You would end up with a left-handed helix instead of a right-handed helix. The normal form of DNA is exclusively a right-handed helix. This is determined by the overall stability of the stacking interactions, which favor right-handed helices.

There are rare forms of DNA (e.g. Z-DNA) that are left-handed. The normal form of DNA is B-DNA.

When you see the two forms side-by-side it's easy to see that they are different but when you see a single depiction of DNA it's pretty hard for most of us to tell whether it's the correct form or the incorrect form. I'm not very good at it. In fact, I almost published the incorrect form in my first textbook. A graduate student/science writer named John Challice saved me from embarrassment by pointing out the error. (He's now a bigwig at Oxford University Press in New York.)

How do you tell them apart? Think of the helix as a spiral staircase and imagine which way you will be turning as you descend the staircase. If you will be turning to the right as you descend then it's a right-handed helix.

If you know this stuff then you can check published drawings of DNA to see if they are correct. If they are not then you have a right to be skeptical about the quality of the work that's attached to the drawing. If it's a book about DNA or genomes and the author gets the structure of DNA wrong then caveat emptor.

This came up recently in comments about one of my recent posts [How the genome lost its junk according to John Parrington]. I've pasted in a copy of the cover of the book so you all can practice your new knowledge of DNA structure.


38 comments :

  1. If left-handed DNA (e.g., Z-DNA) had been the original DNA that organisms used, would the helices be left-handed? And would it have worked just as well as right-handed DNA?

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    1. Yes, and probably no.

      Z-DNA has severe sequence restrictions and that would greatly limit its usefulness. See Z-DNA.

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    2. I took the question to mean if the structure were of opposite chirality, not just turning around in the opposite helix.

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  2. Another topological detail that should be mentioned is that if you flip a right-hand helix you still get a right-handed helix.

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  3. I'm not good at determining handedness from pictures either, but I can count base pairs, and there are way too many of them per each turn of the helix on this picture. Ridiculously many in fact. Who draws these things?

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    1. I can't tell handedness either without doing a lot more work than I care t o do. Once (40 years ago) I was teaching a class how to make models of DNA with kits that we had then. One of the students told me that my model DNA was left-handed. Unfortunately I couldn't tell if he was right. On the other hand I can also count base pairs, and, of course, you are right, and there are far too many. If the author approved the cover design he should be ashamed of himself, but I don't think authors are always consulted about the covers of their books.

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    2. You just have to concentrate on the helix turns in the front. If the DNA is right-handed it goes from the lower left to the upper right.

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    3. If one has any DIY experience, it may help that "proper" right-hand DNA is like a normal screw or bolt (tightened by turning it clockwise). It doesn't work for people who can't tell clockwise from anticlockwise ;)

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  4. Readers should not miss Tom Schneider's Left Handed DNA Hall of Fame. If you want to see all entries go here
    He mentions a picture from a book of George Gamov (who played some role in the discovery of the genetic code) which shows a left handed DNA model displayed on the Seattle World's Fair 1962. From other pictures from the Seattle Times and the digital collection of the United States Science Exhibit, U.S. Department of Commerce, World's Fair in Seattle, 1962. we learn that there were two DNA models. A correctly right-handed one displaying every single atom and the left-handed one visualizing adenine, guanine, cytosine, thymine bases as four card suits which to my best knowledge was Gamow's idea. A third DNA model correctly displaying right-handedness remained on display in the basin of the fountain of the United States Science Pavilion until today.

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    1. Tom Schneider's Left Handed DNA Hall of Fame.

      Your link gives me a 404.

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    2. My comment on this seems to have disappeared (or else I forgot to post it), but your link to Tom Schneider's Left Handed DNA Hall of Fame gives me a 404.

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    3. Yes. The new link works fine. For some reason the post I thought was missing was indeed missing a few minutes ago, but now it is there, so I posted the same thing twice.

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    4. Sorry, the link to the third DNA model of the Seattle World's Fair 1962 was wrong it should have been http://thefinchandpea.files.wordpress.com/2013/01/img_3438.jpg?w=500

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  5. The DNAs were also part of the promotional film "Century 21 calling" which you will find here.

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  6. I'm pretty certain that the handedness stems from the fact that the base pairs themselves are not right/left-symmetrical. That is, they pack denser one way then the other (though both ways pack denser than untwisted).

    The interesting aspect here, to me, is that the twisting direction of the helix seems to be 'infectious'. That is, while two 'rungs' can twist either right-handed or left-handed, where right-handed is more attractive (pun intended), the third rung either cannot twist the other way, or is at the very least extremely unlikely to do so. And that works the same for any three rung pairs you can have (each of which has two possible combinations and two possible basic orientations, from the four bases). This suggests to me that the main force here is in the common part of the base molecules, which is the part that forms the rails of the ladder, so to speak (the other part is what forms the rungs and contains the actual data).

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  7. An about 50 years old copy of the correct DNA model displayed during the Seattle World's fair can be found in the entrance hall of the Institute for Genetics of the University of Cologne, Germany. It has been purchased by the founder of the institute Max Delbrück who must have been quite influencial for the 1962 Seattle science exhibition because a model of one of his T-phages was on display as well. It would be interesting if anybody here has some information on where the Seattle models are today.
    BTW, the exhibition on biology started with a reference to Charles Darwin and evolution.

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  8. This is Off Topic but relevant, so I'll be brief.
    In 2006 you flatly stated "Roundup is Safe"
    Reuters's headline dated 20 March says "Monsanto weed killer can 'probably' cause cancer: World Health Organization".
    By the way, I have no issue with genetically modified organisms; my concern is with biocide synergistic ones.

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    1. Roundup is safe by any meaningful definition of "safe."

      People have been trying to prove that Roundup is dangerous for twenty years and they've spent tons of money. Roundup is sprayed from airplanes in fairly populated areas and average citizens like me have been using it around their homes for ages. There has been plenty of opportunity to show that it's dangerous but nothing has turned up. Nothung that has been substantiated.

      Isn't about time to admit that it's safe and move on?

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    2. I suspect that most of the people who claim that Roundup is carcinogenic know nothing about biochemistry, and nothing about the causes of cancer, and don't know what Roundup is. Although there is always the possibility that one is wrong, I'd be surprised if N-(phosphonomethyl)glycine were carcinogenic, or even significantly toxic for organisms that don't have the shikimate pathway.

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  9. "I've deliberately drawn it with only six or seven base pairs per turn instead of the normal 10-11 base pairs per turn because it's easier to see the shape of the helix."
    In fact, the cartoon on the right is correct. There are 10 base pairs per Compete 360° twist of the helix, or five per half-twist, just as shown.

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    1. Good point. My bad. I'd forgotten that I made the effort to depict it correctly and then I miscounted when I wrote the post.

      I feel stupid. (Not the first time.)

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  10. The drawing might be DNA in the process of active transcription.

    It think it is rather immature to judge a book by the Z-DNA cover, while Moran does not even seem to realize that these structures form all the time during active transcription supercoiling-uncoiling.

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    1. Nice try, to propose that the artist was being so accurate, yet forgot to draw in the transcription bubble and included 3x too many base pairs per turn.

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    2. @Peer Terborg

      Are you seriously suggesting that I don't the structure of transcription bubbles and supercoiling as well as you do?

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  11. Z-DNA is possibly beyond the bubble and considering the turns...it is just recoiling again ?

    In sum: judging a book by the cover is immature nitpicking.

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    1. In this case I will judge the book by more than its cover but the cover is relevant.

      BTW, do you think it's okay to judge people by the comments they make on my blog? Just askin'.

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    2. From the comments it usually gets immediately clear we deal with (extremist) atheist or theist. But thats not a judgement, just a conclusion.

      They may have lost the god-sensing part of the genome, would be may guess, and that makes it forgiveable.

      As you know, "Everything is determined, the beginning as well as the end, by forces over which we have no control. It is determined for the insect, as well as for the star. Human beings, vegetables, or cosmic dust, we all dance to a mysterious tune, intoned in the distance by an invisible piper.”

      Including the recombinations taken place in the gametes of their parents and forbares. You can'rt control them. To know that is to understand that, and to understand all is to forgive all.

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    3. Hey Peer,

      I understand that "the recombinations taken place in the gametes of [your] parents and forbares(sic)" made you a fucking idiot and that you can't control this.

      But I forgive you.

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    4. And immediately a deletion-mutant jumps in to proof my case....

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    5. The point is that you guys really aren't aware of the data of the 1000 genomes project...

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    6. "The point is that you guys really aren't aware of the data of the 1000 genomes project..."

      Genomes that clearly and unambiguously show that atheists have deletions that won't let them fall for the bullshit written by some Peer Terborg IDiot.

      It's written in ACTGs!

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    7. Another indel-mutant feels addressed....

      Thanks indels for making my point.

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    8. indel-mutants of the world recombine - you have nothing to lose but some base pairs

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    9. Everything is determined, the beginning as well as the end, by forces over which we have no control.

      Sorry, but we've known for nearly 90 years now to a mathematical (un)certainty that our universe doesn't work that way. Before that time, we thought as we understood things to finer and finer levels we'd get to a point where in principle the future was calculable. But in 1927 we learned that at the lowest, most fundamental levels, the future - in fact, the present - is uncertain and fundamentally incalculable.

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    10. Thanks indels for making my point.

      Your point? In concluding that you actually made a point, you have, ironically, actually made quite the point. It just isn't what you think it is. But I'm sure you are more accustomed to blogs where that sort of rhetoric is considered brilliant and decisive.

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  12. Twisting the DNA as suggested by the circular arrows would produce a left-handed DNA. Contrary to the illustration.

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