This paper describes a collaborative activity for students, which allows them to build simplified models of individual nucleotides, DNA, and RNA using ZOOB building blocks. These models help students learn about nucleic acid structure and the process of transcription. In addition, students learn how to work in groups as well as practice critical thinking and deductive reasoning while building these models.
The core concepts of information storage and the relationship between structure and function are outlined in Vision and Change in Undergraduate Education: A Call to Action (AAAS, 2010) as topics students need to understand to be considered scientifically literate (AAAS 2010; Woodin et al., 2010). DNA structure efficiently stores and transmits genetic information because complimentary nucleotides form a code that is the basis for the molecular processes of replication, transcription, and translation. It is necessary for students to understand this relationship between DNA structure and function; however, although many undergraduate biology students can recite base paring rules of DNA, they fail to connect these facts to the larger concepts of DNA being able to self-replicate or that a single strand of DNA can act as a template for RNA synthesis during transcription. Additionally, teaching the flow of information from DNA to RNA to proteins, the central dogma of biology, is a fundamental concept for students to learn in general biology so they can apply it to advanced topics presented in genetics and molecular biology courses.
When educators and students draw DNA, the diagrams often consist of parallel horizontal lines, to represent the DNA backbone, to which they add vertical “rungs to the ladder” representing the nitrogenous bases. Although a convenient representation, these drawings do not accurately represent DNA and can lead to misconceptions about nucleotide structure and how DNA and RNA are synthesized. The author has observed this “rungs on a ladder” misconception in class, and even when this activity was utilized, several groups disregarded the instructions and started clicking pieces together to form a long phosphate sugar backbone. Once students were set back on track following the instructions, they first built nucleotides and then used the nucleotides to build DNA and RNA models. This activity can be modified so that it is appropriate for introductory biology students who are learning about nucleic acid structure and function for the first time, or for students in advanced biology classes, such as molecular biology or genetics, to reinforce their knowledge. Next Generation Science Standards indicate the development and the use of models is one of the eight essential practices for K-12 students, and at the high school level, students should be able to use these models to predict phenomena (NGSS, 2013). This activity can be adapted to predict amino acid sequences from a given DNA sequence, or it can be used to work backwards, having students build a plausible DNA model representing the nucleotide sequence that would give rise to a given amino acid sequence, thus reinforcing the central dogma.
Building models is a longstanding technique in molecular biology. Scientists have created DNA models dating back to the original “double helix” model builders, James Watson and Francis Crick. Molecular modeling activities have been used to complement molecular biology and chemistry education, and a number of techniques have been described (Bohrer, 1997; Malacinski & Zell, 1996; Schollar, 2003; Whitlock, 2010). Many models are able to demonstrate DNA replication (Malacinski & Zell, 1996) and DNA recombination (Bohrer, 1997). However, these models could be improved if they were able to demonstrate the structural complexity of DNA as well as molecular processes. Alternatively, some structurally accurate models for DNA are rigid and do not accurately reflect the structural flexibility of DNA (Schollar, 2003). One of Schollar's models uses the familiar children's building toy, Legos, to create an accurate three-dimensional model. However, this model cannot easily be used to model transcription or replication of DNA (pp. 26–30). This activity uses models that reflect similarities, such as the similar imidazole ring in purine nucleotides, as well as differences, as in the pyrimidine rings of the nucleotides. The models presented here are able to reveal proper base pairing between nucleotides and can be manipulated to demonstrate transcription, giving a visual representation to these abstract concepts. Also, in the activity developed to accompany this model, student groups are asked to apply what they learn to answer critical thinking questions to help reinforce their understanding of the material. Molecular modeling has been shown to increase student learning of DNA structure (Altiparmak & Nakiboglu Tezer, 2009). Additionally, student-centered activities have been shown to promote their learning and the development of critical thinking skills (Armbrewster et al., 2009).
This paper presents a collaborative activity in which small groups of students build three-dimensional models of nucleotides, DNA, and RNA using ZOOB building pieces. Zoology, ontology, ontogeny, and botany, or ZOOB, building toys were designed specifically to model how simple subunits can combine into more complex molecules (Micah Moses 2010a, 2010b). This simple yet dynamic representation is able to model some of the three-dimensional features of the DNA and RNA macromolecules, while retaining the flexibility to model the process of transcription, to help students better connect with these complex structures and processes. The ZOOB set includes directions for building a DNA model, but the model contains some pieces that are purely structural, such as a center axis that has no correlation to components of actual DNA, and only serve to support the double helix shape (Figure 1). Additionally, the model included in the ZOOB kit lacks four distinct nucleotides, using only two different pieces for the nitrogenous bases (Figure 1). For these reasons a new model was created, by the author, that more accurately reflects the structural components of nucleic acids. This new model does away with the structural center axis and contains distinct deoxynucleotides as well as ribonucleotides to better model the discrete internucleotide interactions, and includes an activity also developed by the author to teach about nucleic acids (see Supplemental Materials).
The DNA model presented here is also structurally flexible, allowing students to manipulate the helix, unwind and separate the strands, and insert RNA nucleotides to create an RNA/DNA hybrid to model transcription.
ZOOB sets in several sizes are available from large retailers such as Target or Amazon. Although some commercially available ZOOB sets form specific models such as cars or dinosaurs, many of the sets are simply “buckets” of pieces with directions to form several different items, depending on the size of the set. For this activity, two of the largest set, ZOOB 500, containing 100 pieces of each type (Figure 2) are needed so that instructors can make simple molecular model kits for each group of students, consisting of only the ZOOB pieces needed for the models. The author divided the pieces into six sets for a class of 24 students, but up to eight sets could be made from two ZOOB 500, which can accommodate 32 students in groups of four. For each group of students, a DNA/RNA molecular model kit can be compiled using the following components from the ZOOB 500 kits:
ZOOB pieces in total: 24 red, 12 blue, 12 silver, 6 yellow, and 6 green
For the DNA model: 20 red, 8 blue, 4 silver, 4 yellow, 4 green
For the RNA model: 8 silver, 4 red, 4 blue, 2 yellow, 2 green
Quart resealable bags to store the separated DNA and RNA model pieces
Gallon resealable bags to store each kit
The quart resealable bags are used to store the different pieces needed for the DNA and RNA models and are marked “DNA model” and “RNA model,” respectively. Including one each of the DNA and RNA model quart bags in a gallon resealable bag completes a molecular model kit.
Objectives and Procedure
The first objective of this activity is to build simplified models of nucleotides, DNA, and RNA. Another objective is for students to use these models to determine an amino acid sequence using the universal genetic code table. In addition to building the DNA and RNA models, students groups deduce the structure of the individual nucleotides, following instructions written as a series of statements or rules. This provides students with the opportunity to work on their deductive reasoning skills, which are needed to ask questions about science and to learn to think like a scientist.
Each group of students is given one of the molecular model kits along with a handout of instructions and questions to be answered by each group. The first task for the groups is to study a diagram of a generalized nucleotide and the nitrogenous bases (Figure 3) and to describe the overall structural differences between pyrimidines and purines.
Next, the students are asked to describe what portion of the purines is similar in both adenine and guanine. Students usually notice the double ring structure of the purine compared with the single ring of the pyrimidine nitrogenous bases, and that the ring connected to the sugar, the imidazole ring, is similar in both purines. This primes students for nucleotide model building by conceptualizing the structural difference between the two types of nitrogenous bases. Groups are then allowed to deduce the structure of the individual DNA nucleotides using the quart resealable bag containing the DNA model pieces, along with the following set of rules and a picture of the ZOOB toys with the different regions defined (Figure 4).
Sixteen red pieces will be used to represent the phosphate, and deoxyribose portion of the nucleotides (Figure 4).
The nitrogenous bases are composed of the following pieces: 8 blue and 4 each of red, green, yellow and silver (Figure 2).
All nucleotides have a unique structure and must be made of different combinations of pieces.
All nucleotides have a red piece as the phosphate/deoxyribose.
Nitrogenous bases must attach via a claw to the red bodies from the first bullet.
Nitrogenous bases can be made of one or two pieces (Figure 5).
A silver piece is never part of a two-piece nitrogenous base.
A red piece is never a one-piece nitrogenous base.
All blue pieces must attach to the red phosphate/deoxyribose (Figure 5).
If the nitrogenous base is composed of two pieces, those pieces cannot be the same color.
All two-piece nitrogenous bases must be linear attachments.
There are no claw-to-claw connections.
There are no notch-to-notch connections.
Eventually, through the deductive reasoning process, all student groups end up with the same ZOOB piece combinations for the nucleotides. This makes the nucleotide models interchangeable among groups, and the individual group models can be combined to form one large class DNA. The nucleotide construction activity ensures that the structures of the nucleotides allow for only one “head to claw” interaction with a second nucleotide, mimicking actual molecular interactions (Figure 5).
It also helps reinforce the concept that DNA is made from nucleotides. Once groups have finished constructing the nucleotide models, they are asked to record their nucleotide piece combinations, followed by a class discussion in which students present their groups' ideas about which models best represent pyrimidines versus purines, along with a rationale. Students use the models and refer back to the diagram to see which portions of the molecules—the phosphate, sugar, and nitrogenous base—are represented by the pieces in their models. Students are able to see that on the red piece represents the phosphate deoxyribose region, the head represents the 5' phosphate, the body represents the deoxyribose, and the claw represents the 3' hydroxyl group. They make the connection between the double ring structure of the purine nitrogenous base versus the single ring of the pyrimidine nitrogenous base, and the two-piece versus one-piece nitrogenous bases of the models (Figure 3, Figure 5).
While students are constructing their models, the instructor circulates among the groups. Student questions are usually answered with another question to lead groups in the direction of the answer to their original question. This helps to keep the students thinking as opposed to giving up as soon as they encounter a problem. When students present their ideas about which structure corresponds to the pyrimidines or purines, the instructor encourages them to justify their choice based on structural similarities and to describe their response in terms of these similarities.
Once all groups have constructed the nucleotides, they proceed with building DNA models. To construct the DNA macromolecule, groups use two of each type of nucleotide and connect them randomly via their phosphate/deoxyribose pieces. This process reinforces that DNA is synthesized by joining nucleotides. Students then use the remaining nucleotides to construct the opposite strand. The ZOOB pieces have heads and claws corresponding to the 5' phosphate and 3' hydroxyl; the DNA strands students build can be made antiparallel simply by reversing the direction of the pieces on the nontemplate strand. Since the DNA model is constructed by joining nucleotides, each with a unique structure (Figure 5), students have the experience of using one strand as a template to create the complementary strand. The second strand will be complementary to the template because the nucleotide models only connect to one other nucleotide model via their nitrogenous base regions, mimicking the adenine-to-thymine and guanine-to-cytosine hydrogen bonding across the DNA strands.
One limitation of the ZOOB models presented in this paper is that they are unable to represent the difference in the number of hydrogen bonds between adenine and thymine versus that between guanine and cytosine. The model constructed by the students prevents incorrect base pairing because it would involve either a head to head connection, which will not physically connect, or a claw to claw connection, which creates a rigid ball that will not allow for twisting of the DNA model into a helix, or the model will have an incorrect width, either too wide or too narrow in a particular section causing the pieces to come apart. Groups will have a model of DNA that is eight base pairs long and can be twisted into a double helix.
Once groups have completed their models, they answer the following questions to reinforce the base pairing concepts: With what type of nucleotide does each pyrimidine base pair? Why is it able to pair with this type of nucleotide? Does it always pair with the same nucleotide?
After discussing their answers as a class, the group models are first flattened (Figure 6a), combined into one large class model, and retwisted into a double helix. Using this model students can visualize the three-dimensional structure of DNA on a larger scale (Figure 6b). Although the ZOOB model presented here displays the three-dimensional structure of DNA, it does not reflect the major and minor grooves.
With the DNA model completed, groups begin working on making RNA nucleotides. Constructing RNA nucleotides also involves using deductive reasoning, with the following rules:
The four nucleotides of DNA are adenine, guanine, cytosine, and thymine. In RNA, thymine is replaced by uracil; like thymine, uracil is a pyrimidine nucleotide containing only one ring.
In the resealable bag marked “RNA” are the eight silver pieces representing the phosphate/ribose in RNA.
There are enough pieces to make two of each type of RNA nucleotide.
The nitrogenous bases adenine, guanine, and cytosine have the same color combinations as in the DNA model (Figure 7).
Once completed, student groups are directed to compare the nitrogenous bases of RNA and DNA; nitrogenous base diagrams are given at the outset of the exercise so that students can determine which RNA nucleotide is different and therefore is uracil. Using this information, they can then determine the identity of all the nucleotide models for both DNA and RNA.
After taking the time to build nucleotides and a DNA model to show the complementarity of DNA strands, students can then manipulate these DNA models to study the process of transcription. The advantage of the ZOOB DNA structural models presented here is that they are dynamic; they can be easily twisted into a double helix, and then unwound and separated into individual strands onto which RNA nucleotides can be added, modeling the process of transcription (Figure 8). Student groups are asked to separate the strands and build an RNA molecule using their RNA nucleotides. This can be done either by breaking the large class DNA model into eight base pair sections for each group, or the class can work together on one longer piece with groups contributing their RNA nucleotides to the larger piece. Once the RNA model is complete, students record RNA nucleotides from 5' to 3' and use the universal genetic code table to translate their RNA model into amino acids (Figure 9).
After completing their models, each group is assigned one of the following higher order learning questions:
Given the amino acid sequence proline, valine, and aspartic acid, construct a DNA and RNA molecule associated with this sequence. How could a single base change in your DNA model cause a change in the amino acid sequence? Where in a codon is a base change most likely to cause a change in amino acid, and why?
Given the amino acid sequence leucine, tyrosine, and tryptophan, construct a DNA and RNA molecule associated with this sequence. How could a stop codon be introduced into this sequence by mutation? Which amino acid is least likely to be changed by a single base mutation, and why?
Based on your modeling of DNA and transcription, would it be possible to distinguish a nucleotide mismatch? How could this mismatch be structurally represented in the model?
Groups are given 10–15 minutes to discuss their answers. They are expected to use their models to work through their answers. Then each group chooses one person to present their answer to the class. These questions can be used to segue into the topic of mutation and its effects on protein structure and function.
Molecular biology considers many abstract concepts. Research has shown that undergraduate students are often not yet developmentally ready for these concepts, as they are operating closer to what Piaget termed the “concrete operational stage” in which they can think logically about concrete ideas, but are still transitioning to the point where they reason about abstract ideas (Herron, 1975; Malacinski & Zell, 1996; Lawson, 1992). The ability to use deductive reasoning is associated with more abstract reasoning. This activity for building nucleotides allows students to practice deductive reasoning in a low-stakes environment to develop their skills with this type of reasoning.
This activity was carried out at an urban community college with a diverse student population coming from over 100 countries and speaking more than 70 languages. Many of our students have not encountered a modeling activity in their middle school or high school science classes. When this class activity was initially carried out by groups of four students, some members of the group seemed to have little to do. Pairs or groups of three may help to allow all group members to work with the models. As this modeling activity is one of the first activities done in this genetics class, it can serve as a reference point they can return to as the course continues and discusses different types of mutations. In the future, the models created by the student groups will be saved and returned to them when the course goes into more detail about mutations and classical Mendelian genetics so that students can see that changes in phenotypes ultimately go back to changes in DNA nucleotide sequences. Students reported that they enjoyed the activity, and it seemed to hold the students' attention without prodding them to stay on task. Students commented they were now able to “see” and understand why one base had to pair with another, and that it was the only way they could pair, and also that they liked having something they could “see and touch.” One student reported having a better understanding of how a DNA molecule was constructed, and that this activity would have been helpful when initially introduced to the concept of nucleic acid structure. The students appreciated being able to manipulate structurally complex DNA and RNA models that could be wound and unwound as needed to mimic DNA transcription.