In the Classroom
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A Unique Demonstration Model of DNA Jonathan P. L. Cox Department of Chemistry, University of Bath, Bath, BA2 7AY, United Kingdom;
[email protected] Watson and Crick proposed their functionally-suggestive structure for the B form of DNA—later shown to be essentially correct (1)—over 50 years ago (2, 3). Despite this fact and despite the fact that genetic fingerprinting (4) has made DNA a household word, there is no single physical model of DNA for the classroom—or for the general public—that both accurately conveys its structure and readily demonstrates its two principal biological functions, information storage and replication. Existing physical models of DNA (5) include a cut-out paper helix (6), a ribbon-like model (SciVon) (7), space-filling models (CPK, Molymod) (8, 9), and ball-and-stick models (Nicholson and Cochranes) (10, 11). Each of these models has a number of drawbacks (Table 1). For example, the balland-stick models, while illustrating the structure of DNA in atomic detail, do not highlight the functional aspects of DNA, and they are time-consuming to build. Probably the best currently available model is miniDNA (Spiring Enterprises) (5, 9). This model is a more abstract representation of the molecular structure of DNA, with the bases, deoxyribose sugars, and phosphate groups represented by colored shapes. The model, which compared to ball-and-stick models is quick to assemble (∼25 minutes), demonstrates some important structural features of DNA (Table 1) and is also
able to show replication. It has several drawbacks, however: it is difficult to alter the sequence of base-pair units; maintaining the structure requires a central supporting rod plus spacers between adjacent base-pair units; and it must be removed from this supporting rod (and spacers) in order to replicate it—it cannot be replicated in situ. General Description of the DNA Model The mechanical model presented here addresses some of the shortcomings of the currently available models of DNA described above (Table 1). Importantly, the model conveniently demonstrates the ability of DNA to encode information and to replicate, while at the same time representing several of the gross architectural features of idealized B-DNA, albeit in abstract form. Thus different base-pair sequences can be put together and taken apart rapidly (it takes about a minute to put together a version of the model comprising 11 base-pair units) and unlike any other currently available model, replication can be performed in situ. In addition, the model is to scale, being 50 million times larger than its molecular counterpart. It also rests on a simple base and does not require a central supporting rod. Although in its present form the model is made of hard plastic, equally it could be made of other materials such as foam or rubber.
Table 1. Structural, Functional, and Practical Attributes of Currently Available Demonstration Models of DNA Attribute
Cut-Out Helix
Ribbon
Space-Filling
Ball-and-Stick
miniDNA
Bath Model
∆
∆
∆
∆
∆
∆
“Antiparallel” strands
∆
—
∆
∆
∆
∆
Major and minor grooves
—
—
∆
∆
∆
∆
10 Base-pair units/turn
∆
—
∆
∆
∆
∆
Sugar-phosphate backbone highlighted
∆
—
∆
∆
∆
—
Relative sizes of base units emphasized
∆
∆
∆
∆
∆
∆
Base-pair unit specificity
∆
—
∆
∆
∆
∆
Base-pair units perpendicular to helical axis
∆
∆
∆
∆
∆
∆ ∆
NStructure Right-handed
Base-pair units close-packed
—
—
∆
—
—
To scale
—
—
∆
∆
∆
∆
Atomic detail
∆
—
∆
∆
—
—
Flexibility
—
∆
—
—
—
—
Ability to show A and Z forms of DNA
—
—
∆
∆
—
—
Ability to show local variations in structure
—
—
∆
∆
—
—
NFunction
Sequence of base-pair units readily altered
—
—
—
—
—
∆
Able to show replication
—
∆
—
—
∆
∆
NPractical
Easy to construct
—
∆
—
—
∆
∆
Self-supporting
—
∆
—
—
—
∆
NNOTE: The symbol ∆ indicates that the model possesses the attribute in question.
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In the Classroom
The model is assembled from two types of block: a large block representing the two purine bases, adenine (A) and guanine (G), and a small block representing the two pyrimidine bases, cytosine (C) and thymine (T) (Figure 1). The different bases can be distinguished on the basis of color. Each block has a short peg on one of its planar surfaces and a complementary hole on the opposing planar surface (Figures 1A and B). A neodymium–iron–boron (NdFeB) magnet lies within the peg; another NdFeB magnet lies just beneath the hole. Purine and pyrimidine blocks interact via complementary helicoid surfaces (Figure 1A) to give units analogous to the A:T and G:C Watson–Crick base pairs (Figure 1B). The two blocks comprising a base-pair unit are held together by
a pair of NdFeB magnets lying within the blocks, close to the complementary surfaces. Block pairing is made specific by reversing the polarity of the magnets, such that, for instance, a large blue block attracts a small green block, but repels a small yellow block, and a large red block attracts the small yellow block, but repels the small green block. Overall, the base-pair unit is shaped like a double-edged axe, with two helicoid grooves, one twice as deep as the other, cut into its side (Figure 1B). The planar surfaces of the base-pair unit are displaced by 36⬚ with respect to one another. Each planar surface has one peg and one hole (Figure 1B) and the unit has a twofold axis of symmetry—flipping it over gives the same aspect. Details of how to construct the blocks are given in the Supplemental Material.W Assembling the DNA Model To assemble the model the base-pair units are stacked on top of each other via the complementary peg–hole arrangements on their planar surfaces (Figure 1). A video clip of the assembly process is included in the Supplemental Material.W The resultant structure, which is held together by the magnets in the pegs and holes, is a right-handed double helix with two “strands” running in opposite directions (the direction of these strands is specified by the pegs and holes) and a major and a minor groove (Figure 2). These grooves arise from the smooth propagation of the base-pair units’ helicoid grooves from one unit to another. Both grooves are slightly wider and slightly shallower than the corresponding grooves in B-DNA (12). The overall structure has a twofold axis of symmetry perpendicular to the helical axis. The base-pair units lie perpendicular to the helical axis. There are no gaps between adjacent base-pair units, emphasizing the close-packed nature of B-DNA, a point overlooked in ladder-like representations of DNA. The angle of 36⬚ between the units’ upper and lower planar surfaces leads to adjacent units being displaced by the same angle, which in turn causes the structure to repeat after every 10 base-pair units (Figure 2).
Figure 1. (A) The two building blocks of the DNA model. The small (green) block represents a pyrimidine base, the large (blue) block a purine base. These two blocks interact magnetically via the complementary helicoid surfaces shown towards the center of the picture. Notice the peg on the small block and hole on the large block. (B) The intact base-pair unit. The unit is essentially a cylindrical segment with two opposing grooves cut into its side. The large upper groove forms part of the major groove in the assembled model, the small lower groove the minor groove. The peg on the (red) purine block lies at the center of the arc that divides the base-pair unit in two. The complementary helicoid surfaces shown in Figure 1A are generated by descending this arc through the unit from the upper to the lower surface, rotating it as it descends in a clockwise direction about the vertical cylindrical axis of the block, such that it emerges from the unit having been rotated by 36º. Scale bar: 5 cm.
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Figure 2. The assembled model (11 base-pair units) highlighting the right-handed twist of the double helix and the major (M) and minor (m) grooves. Scale bar: 5 cm.
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In the Classroom
Functional Aspects of the Model The ability of DNA to encode information stems from the ability of the double helix to accommodate any base-pair sequence. Likewise, because the base-pair unit of the model presented here has twofold symmetry and can therefore be added to the stack in either orientation, these units can also be built into any sequence, the sequence being distinguished by the order and identity (i.e., color) of the blocks. To use the model to demonstrate the ability of DNA to replicate, the blocks are first unwound from the main body of the helix. (The strength of the peg-hole links in the model shown allows the unwinding of 8 base-pair units before the structure becomes unstable.) During the unwinding process the blocks pivot about the peg–hole joints linking adjacent base-pair units together. The unwinding process is facilitated by the positions of the pegs and holes on the blocks’ planar surfaces and by the helicoid shapes of the complementary surfaces through which the two blocks interact. Once the helix has been partially unwound, replication is achieved by attaching the complementary blocks. The Y-shaped arrangement generated by the unwinding and attachment process (Figure 3) is not dissimilar from the replication fork formed during DNA synthesis (12). If the demonstration is performed with a small isolated segment (e.g., 5 base-pair units), the last base-pair unit may be replicated by detaching the partially replicated strands and then adding the two relevant complementary blocks. Video clips describing the replication process are available in the Supplemental Material.W
Figure 3. Partially unwound and replicated helix. Complementary blocks have been added to the two exposed blocks at the base of the unwound left-hand strand, and a third block is being added to the next exposed block. Similarly, two complementary blocks have been added to the exposed blocks at the top of the unwound righthand strand.
Jolliffe, Nicholas Jones, Alastair King, Pooja Kumar, Laurie Peter, Gareth Price, Anita Shaw, and Jonathan Williams. I would also like to thank Mark Russell and Nic DelvesBroughton for technical assistance. The model described in this report was built by David Cragie and Ian Buxton of Invicta Plastics Ltd., United Kingdom, based on a prototype supplied by the author. The University of Bath financed this work. W
Limitations of the Model Although the model can be replicated in situ, some care must be exercised during the unwinding process, otherwise the blocks may become stuck. While this situation is perhaps somewhat undesirable, it does introduce a puzzle-like feature into the process that may help to engage the student’s interest. Alternatively, fabricating the model from a softer material, such as foam, rather than hard plastic, might facilitate the replication process. The greater pliability of such a model would also give some idea of the flexibility of DNA, although it would not be able to show extreme examples, such as kinking or supercoiling (12). Another limitation of the model is that it is representative only of B-DNA—it does not account for two other wellknown double-helical conformations, namely, the A and Z forms (12). Nor can it show propeller twisting within a base pair and variation in the rotation angle between base pairs (36⬚ for idealized B-DNA) (1, 12). In other words, it cannot make the point that B-DNA is not perfectly regular, but contains local variations in structure. Furthermore, it does not depict the molecular structure of the bases and the number and nature of the hydrogen bonds between the bases. All these features would be better illustrated with space-filling or balland-stick models. Finally, the model does not highlight the sugar–phosphate backbone of DNA. Again this would be better illustrated with space-filling, ball-and-stick, or miniDNA models. Acknowledgments I would like to thank the following people for helpful discussions: Adrian Bowyer, John Bradley, Ian Jeffery, Anna www.JCE.DivCHED.org
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Supplemental Material
Details of how to construct the blocks, templates for fabricating the model’s blocks from plastic, and video clips demonstrating assembly and replication of the model are available in this issue of JCE Online. Literature Cited 1. Wing, R.; Drew, H.; Takano, T.; Broka, C.; Tanaka, S.; Itakura, K.; Dickerson, R. E. Nature 1980, 287, 755–758. 2. Watson, J. D.; Crick, F. H. C. Nature 1953, 171, 737–738. 3. Crick, F. H. C.; Watson, J. D. Proc. Roy. Soc. A 1954, 223, 80–96. 4. Jeffreys, A. J.; Wilson, V.; Thein, S. L. Nature 1985, 314, 67– 73. 5. National Centre for Biotechnology Education DNA Models Page. http://www.ncbe.reading.ac.uk/DNA50/models.html (accessed May 2006). 6. Van Loon, B. DNA, The Marvellous Molecule, 2nd ed.; Tarquin Publications: Norfolk, United Kingdom, 2003. 7. SciVon Enterprises DNA Model Page. http://www.scivon.com/ dna.html (accessed May 2006). 8. Home Page of Harvard Apparatus (a Harvard Bioscience Company). http://www.harvardapparatus.com (accessed May 2006). 9. Molymod Home Page. http://www.molymod.com (accessed May 2006). 10. Labquip Home Page. http://www.labquip.clara.net (accessed May 2006). 11. Cochranes of Oxford Entry Page. http://www.cochranes.co.uk (accessed May 2006). 12. Stryer, L. Biochemistry, 4th ed.; W. H. Freeman: New York, 1995; pp 787–809.
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