Beaded DNA Replication Fork Necklace

Over the holidays I carved out some time in my beading schedule to treat myself to a new jewelry set. It's another piece of beaded DNA, in the Y-shaped structure of a replication fork.

The colors and design of the necklace came about from a pair of earrings that I made alongside several other pairs of earrings that I wove for Christmas presents. For this pair, I continued the theme of using larger beads for the purines and smaller beads for the pyrimidines: I used 4 mm bicone crystals for A and G, and 3 mm bicones for C and T. I also added little caps at both ends of the earrings for an aesthetic effect.

The problem with these earrings is that I didn't use a seed bead between the crystals and the DNA backbone, which leaves the thread exiting the crystal at an angle. As any experienced beader will tell you, this can make the thread weaken and snap, which was the case when I made these earrings even though I used the stronger fireline thread instead of a nylon thread. As such, I didn't feel comfortable giving away or selling these earrings, so I kept them for myself.

These earrings needed a matching necklace, so I set out to create a beaded replication fork. For the types of beads used in the DNA itself, I added back in a 15° seed bead between the crystals and the backbone, so that the necklace would be stronger than the earrings. I also decided to forego the variation that yields major and minor grooves that you can see in my gene regulation necklace. The resulting necklace less-accurately portrays real DNA in that respect, but it does look closer to real DNA in another; since I used smaller beads for the backbone (I replaced some of the 11° seed beads with 15° seed beads, and the 8° seed beads with 11° seed beads), and a relatively longer set of beads for the base pairs (approx. 9 mm), there are about 11 base pairs per turn of the beaded double helix. B-DNA has about 10.5 base pairs per turn. In all the variations I've beaded on this design, I've only been able to get up to about 8 base pairs per turn until now. (For more on this subject, take a look at Gwen's two crystal DNA pieces - you can really see the effect of base pair length on helical pitch in these pieces).

I call this necklace a replication fork because it depicts how real DNA is replicated; since each base pair is defined (C always pairs with G and A always pairs with T), each strand has enough information to serve as a template for the other strand. Real DNA replicates this way; the double helix is unwound into single strands, and the new strands are synthesized on to the two older strands, one nucleotide at a time. So in this piece, the older DNA is at the focal point of the necklace, and the newer DNA wraps up the necklace towards the back.

For the branch point of the necklace, I left one base pair unpaired so that each daughter strand had enough room to twist up the necklace. I should note that a real DNA replication fork looks quite different than this one; the two new strands are not joined together at the branch point as they are in this necklace, and there are quite a few more bases unpaired at the branch point. The method of replication is also different for each of the two strands because of the antiparallel nature of the strands and the requirement that DNA can only be synthesized in one direction, but that's a story for another time.

The necklace has a beaded custom toggle clasp, woven with a twist on the embellished RAW technique.

Finally, additional Swarovski bicone crystals and Venetian glass rounds complete the necklace.

The sequence used in this necklace comes from the alpha subunit gene of the E. coli DNA polymerase III complex, which is responsible for most of the DNA synthesis in the E. coli cell. The story of its discovery, 24 years after the first DNA polymerase was characterized, is an interesting lesson in persistence and the methodology needed to solve complicated scientific questions. Plus it's the perfect sequence to use for a depiction of DNA replication :)

Beaded DNA Bracelet

As I mentioned in my previous post, a good friend of mine requested a DNA bracelet for Christmas. I wove one for her in a peaches-and-cream color palette:

The bracelet uses the same modifications that I used for my gene regulation necklace, and in this style, 43 base pairs of beaded DNA are needed to reach the length of a bracelet. The bracelet itself is about 7 1/2 inches long, and finished with a simple silver S-clasp.

The sequence in this bracelet is from the human monoamine oxidase A gene, and some versions of this gene are thought to be a factor in several psychiatric disorders. It's an especially great conversation-starter piece for my friend, who's a school psychologist. The protein encoded by this gene is involved in the breakdown of the "happy" brain chemicals serotonin and dopamine, so it's become a key target of antidepressant medications. Interestingly, one study has reported that women with a low-expression version of this gene are happier than other women. However, individuals with a dysfunctional version of this gene have a very rare genetic disorder called Brunner syndrome, which causes several psychological problems. The gene itself is over 90,000 base pairs long, so this bracelet covers only a very small portion of the start of its coding sequence.

I hope that you had a great holiday season, and best wishes for a very Happy New Year!

New Beaded DNA Earrings

I took a break from beaded coffee chemistry to make some Christmas presents, but I didn't stray very far from the realm of scientific jewelry. A very good friend of mine hinted at wanting a DNA bracelet for Christmas, and I just can't turn her down. However, after wrapping my DNA necklace around my wrist and calculating that a bracelet would be about 40 beaded base pairs long, I wanted to test the color palette in mind before I beaded it altogether.

So, I made a few pairs of beaded DNA earrings, making yet more modifications to Gwen's fabulous pattern.

I beaded these earrings without the modifications for major and minor grooves that I used for the necklace, since it takes about 20 base pairs to see the grooves well, and it's difficult to appreciate them in a 10-bp pair of earrings. Instead, for these earrings, I adjusted the sizes of the seed beads in the backbone to make it narrower, and I used 11° seed beads for the bases. I used two seed beads each for the purines, A and G, and one seed bead for the pyrimidines, C and T, since purines are bigger than pyrimidines.

I beaded another pair in silver and the coffee colors sitting on my beading tray from the beaded caffeine molecules. In keeping with the coffee theme, I chose a sequence from the caffeine synthetase gene from the coffee plant, which encodes the enzyme that carries out the final step in caffeine biosynthesis. While the gene itself is nearly 2000 base pairs long, I only beaded the first 10 base pairs for these earrings. Like the pair above, I added a little twist by adding a cap to the bottom end with a sparkly bicone crystal.

There actually are caps on some nucleic acids in biology, most famously in DNA's close sibling RNA. mRNAs contain a 5' cap made of a specially modified G nucleotide, which serves to both stabilize the molecule (since RNA is much less stable than DNA), and to direct it to the ribosomes where it is read to make proteins. However, in these beaded DNA renditions, I must admit that I added the caps for purely aesthetic reasons.

I like how these earrings turned out, although I didn't get them to work without several attempts. To give you an idea, here are several of its prototypes:

Beaded DNA: Chirality

I did some more experimenting with Gwen's beaded DNA pattern, this time delving into differences in DNA handedness, otherwise known as chirality. Like a hand or a foot, a double helix can have either a right-handed or a left-handed structure. You might have noticed in my previous posts that I was favoring the right-handed form for my beaded structures, even though the original design is flexible enough to be twisted into either conformation.

Image by Richard Wheeler, used with permission

The above image shows three forms of DNA; A-DNA, B-DNA, and Z-DNA. The B-DNA in the middle is by far the most common form that exists in biology, and it has a right-handed chirality. The A-DNA on the left is also right-handed, and it exists when DNA is dehydrated enough to form a crystal structure (usually only in the lab). The Z-DNA on the right is the only structure of the three that exists in the left-handed conformation, and it looks quite different compared to B-DNA.

Z-DNA is a little thinner, and the backbone of each strand of the double helix (in red and orange above, and in hematite below) isn't a smooth, ribbon-like path. Rather, Z-DNA has a jagged backbone that zigzags with each pair of bases up and down the double helix. Its major and minor grooves are also less pronounced than in B-DNA. Z-DNA forms rarely in biology, and is generally found in DNA with a specific sequence; in this case, alternating pyrimidine-purine sequences, such as CGCGCGCGCG.

With some tinkering, I was able to create a Z-DNA version of my beaded PI-MtuI sequence. The original B-DNA version is on the right, and the new Z-DNA version is on the left:

To create this version, I first worked up the design using my own variations on Gwen's pattern, but when it came time to peyote stitch up and down the backbones of each strand (at about the 7 minute mark in the pattern), I added two 11° seed beads where I would have added one 8° seed bead. Then I zipped up and down the backbones once more, adding a 15° seed bead at the same place as the 11° seed beads, alternating its placement on either side of the 11° beads so that the backbones zig zag:

The resulting structure is more flexible than the B-DNA version, and not as aesthetically pleasing either, but it remarkably mimics the appearance of Z-DNA. You can even see how the major and minor grooves are less pronounced, and how there are fewer base pairs per turn in this version:

Other forms of DNA exist in biology as well, such as the Y-shaped junctions formed during DNA replication, and the very cool Holliday junctions created during meiosis and in some kinds of DNA repair. However, those structures will have to be topics for another blog post.

Beaded DNA: Gene Regulation Necklace

Continuing with the theme of beaded DNA based off of Gwen's pattern, I figured that it was high time to use this design in a wearable item of jewelry. While I still think that my latest variation would be make a great cuff, I tend to wear more necklaces than bracelets, so I searched for the perfect sequence for a DNA necklace. Here's the final result:

The sequence of this necklace comes from the regulatory region of the lac operon of E. coli, specifically, the 106 base pairs between the start of the CRP binding site, and the start codon of lacZ. Regulation of the lac operon was the first mechanism of gene regulation to be discovered, and it remains the primary example of gene regulation taught in Genetics 101 classes today. 


The lac operon contains the genes necessary for an E. coli cell to digest the lactose sugar, but E. coli prefers to munch on the simpler glucose sugar. Therefore, the genes in the lac operon are only active, or expressed, when there is no glucose around, but plenty of lactose to eat instead. The cell knows to express the lac operon through a system of proteins that monitor the presence and absence of glucose and lactose, and according to these sugar levels, certain proteins will either bind or not bind to regions of the DNA sequence depicted in this necklace. Only when the lactose levels are high, but glucose levels low, will these proteins be in the correct combination to encourage lac operon expression. 

I used silver plated seed beads for the cytosines, capri blue for the guanines, green for the thymines, and purple for the adenines. For any of you who also had to memorize the ideal sequences of the -35 and -10 elements in a genetics class, the lac operon's -35 element of TTTACA is in the center of the above picture. Can you see the string of three green and purple base pairs? The -10 element sits just off-center of the necklace. 

Other than its importance in gene regulation, I chose this sequence for this necklace because it's an example of noncoding DNA, or a DNA sequence that does not serve as a blueprint for a protein. These types of sequences make up over 98% of the 3 billion base pairs of the human genome, and were once called "junk DNA" because they were thought to be of little consequence. Regulatory regions such as this one are just one example of the significance of noncoding DNA.

Plus, it makes a significantly cool necklace :)

Beaded DNA Experiments: Major and Minor Grooves

When we last looked at my variations on Gwen's beaded DNA earrings pattern, I had changed the base pairs in the pattern to more accurately reflect the structure of a B-DNA double helix. I had also started to change the backbones of the structure as well:

Why would I go to the trouble of changing the DNA backbones? I was attempting, (albeit incorrectly, as I shall explain), to introduce major and minor grooves into the beaded DNA. 

Image by Richard Wheeler, used with permission

As seen and labeled in the image above, B-DNA has two grooves formed by the spaces in between each backbone. This detail is quite significant in molecular biology, when you consider that the proteins that read the genetic material in the DNA have two different grooves from which to pick from. Incidentally, since the major groove is wider than the minor groove by over 2:1, it is more-often used than the minor groove.

I originally thought that I had reflected this property of B-DNA by changing the backbones in the 14-base pair structure above. To check, I beaded a longer DNA structure of 29 base pairs. The sequence in this structure is that of the recognition sequence of the homing endonuclease PI-MtuI from Mycobacterium tuberculosis.

Unfortunately, this structure does not show the major and minor grooves that I was aiming for. The change in the backbones also made it more unstable than the original. 

I revisited my notes from my previous doctoral coursework, and reminded myself that it is not really the backbone that gives DNA its major and minor grooves: it's that the base pairs are offset from the backbones. You can think of it as a ladder where the rungs do not go through the center of the sides, but are instead sitting on the top or the bottom of the sides, like how railroad ties sit below their tracks and not through them.

After a couple of attempts, I managed to achieve this effect with the DNA pattern. 

To do this variation, I picked up an 8°, 11°, and 8° instead of the bugle bead called for at about 3:30 minutes in the original pattern, also changing the colors of the surrounding 11°s to match the base pairs. The colors between all four base pairs are not balanced, but that's by design, since the pyrimidines, T and C, are smaller than the purines, A and G. I used three seed beads of the same color between the base pairs for the backbone. To make the base pairs pucker up above the backbone, I skip the center 11° when passing through the beadwork again at about 4:00 and 4:20. The rest of the double helix is woven essentially the same as the original pattern. 

A 12-base pair structure woven with this method seemed to show both the major and minor grooves that I was going for:

(Thanks to lovelyfailed for this color palette, "Soapbox Parade")

Indeed, the offset base pairs can be observed by looking straight down the double helix.

But just to make sure that it worked on a larger structure, I wove the 29-base pair sequence from PI-MtuI once more, and I was pleased to find that it showed the same effect: 

I don't know about you, but I find this variation... Quite groovy! It's quite the likeness of the real thing:

I'm certainly not done with this pattern, but I'm very pleased with how this variation turned out. It's still a little large for earrings, but I bet that it would make a nice cuff! I think that a cuff-sized sequence would be about 55-60 base pairs long... Now I just have to find the right sequence!

Do you have a favorite DNA sequence?

Beaded DNA Experiments: Base Pairing

A few months ago Gwen Fisher published a video using Doceri software on how to weave a pair of DNA double helix earrings using seed beads and thread. As a molecular biologist by training, I was completely enamored with this design and immediately set out to play with it (all the while kicking myself for not coming up with the idea first!), but I've only now gotten around to writing the first of what will be several posts on my variations on this pattern. If you haven't already seen her free video on how to make your own pair of DNA earrings, check out Gwen's blog for all the important details. 

I first tried this design on a short random sequence of eight base pairs:

I managed to get the design to work the first time, using significant tension in the second and third rounds of the design to get it to twist. The helix actually started to twist while I was beading the second round.

After trying out this pattern, I immediately wanted to modify it to make it look closer to the structure of real DNA The biggest difference between this design and a DNA double helix is that the bases, consisting of A, G, T, and C, are on the "rungs" of the DNA ladder, not on the sides. 

Image by Richard Wheeler, used with permission

The image above shows the chemical structure of B-DNA, the most common form of DNA. The bases are the flat ring structures containing the blue nitrogen atoms. The thymine and cytosine, or T and C bases, are called pyrimidines and have only one ring. The adenosine and guanine, or A and G bases, are purines, contain two joined rings, and are therefore somewhat bigger than the pyrimidines.

Each side of the DNA ladder, what we call the "backbones" of each of the two DNA strands that make up the double helix, is made up of a repeating sequence of sugars and phosphates. You can see in the image above that there is one sugar (the non-flat ring next to each base, containing no nitrogen or phosphorus) and one phosphate (made up of yellow phosphorus and red oxygen atoms) for each base. Therefore, the important genetic material in DNA is confined to the inner part of the structure. 

One other important feature of DNA is that, except in rare cases, A will always pair with T, and G will always pair with C. This is why DNA sequence databases such as the public National Center for Biotechnology Information will list the sequence of only one of the two strands; if our sequence is:

AGCCATATGAC

..we can match each base in the sequence with its partner to get the sequence of the other strand:

AGCCATATGAC

TCGGTATACTG

I tried to incorporate this aspect of DNA to modify Gwen's design to use color-coded twisted 6 mm bugle beads for the base pairs. I also changed the colors of the DNA backbone to solid blue for the 15° and 11° seed beads, and capri blue for the 8° seed bead, to try and mimic the repeating sugar-phosphate structure.

From a beadweaver's point of view, the structure works up and holds its twist just as well as the original. But the molecular biologist in me really wanted to see all four types of those bases. 

So I switched to 8° seed beads in place of bugle beads for the bases; two seed beads for the purines, and one for the pyrimidines, and also color-coded the 11° seed beads on either side to match its associated base (I also changed the backbone a little bit, but that's a topic for another post):

I like this arrangement much better. It results in a somewhat thicker helix, but it's much more biologically accurate. It would probably work better in a pendant or a cuff than in earrings. 

Gwen also tackled this arrangement by using 8° seed beads and a 3 mm firepolished crystal for each base pair, resulting in a slightly larger helix.

I'm still not done creating further variations on this design, but those are topics for future blog posts. Next time I'll talk about DNA's major and minor grooves...

Have you ever tried incorporating ideas from your day job into your beadwork? How did it work?