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Evolution is a main concept in biology, but not many students understand how it works. In this article we introduce the game DNA Re-EvolutioN as an active learning tool that uses genetic concepts (DNA structure, transcription and translation, mutations, natural selection, etc.) as playing rules. Students will learn about molecular evolution while playing a game that mixes up theory and entertainment. The game can be easily adapted to different educational levels. The main goal of this play is to arrive at the end of the game with the longest protein. Students play with pawns and dices, a board containing hypothetical events (mutations, selection) that happen to molecules, “Evolution cards” with indications for DNA mutations, prototypes of a DNA and a mRNA chain with colored “nucleotides” (plasticine balls), and small pieces simulating t-RNA with aminoacids that will serve to construct a “protein” based on the DNA chain. Students will understand how changes in DNA affect the final protein product and may be subjected to positive or negative selection, using a didactic tool funnier than classical theory lectures and easier than molecular laboratory experiments: a flexible and feasible game to learn and enjoy molecular evolution at no-cost. The game was tested by majors and non-majors in genetics from 13 different countries and evaluated with pre- and post-tests obtaining very positive results. © 2013 by The International Union of Biochemistry and Molecular Biology, 41(6):396–401, 2013
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In science education, Evolution is a central concept that is approached from different perspectives (Anthropology, Genetics, Paleontology). However, students do not understand easily how it works , especially at molecular level. It is difficult to link the processes of formation of functional molecules with the action of the selection—sometimes perceived as the result of mysterious forces of Nature on living beings [2, 3]. Laboratory practices are illustrative of the techniques employed for studying DNA, but indeed are not enough for understanding molecular evolution; teachers must provide theoretical background to acquire knowledge on genetic concepts and properly establishing links between them . Learning molecular genetics and evolution touching nucleotides, making proteins, inducing mutations, obtaining the fittest protein would be perfect for students, but unfortunately it is not possible because molecules are so small.
Theoretical background in genetics and evolution may be acquired out of standard lectures, which strongly rely on the personal communication skills of the lecturer. Students learn better through interactive courses than in traditional classes [5-7] because active learning has positive and motivational effects [8-10]. On the other hand, collaborative learning stimulates learning gains  and students benefit especially from group activities . A good and stimulating learning environment is essential for optimal and durable acquisition of new knowledge . Instead of working independently in an isolated context, significant interactions between students make it easy to learn . Students learn better in an easy and pleasant environment, and the ideal is to employ didactic tools that link learning contents with student's own life and experience [15-17]. An example could be games [10, 18], which are generally associated with enjoyable free time rather than with academic routine. Didactic games are good tools for problem-based learning  because they facilitate the acquisition of educational contents in a playful way. They are especially suited for undergraduate students, the critical audience in introductory biology and genetics courses .
The didactic innovation we describe here, DNA Re-EvolutioN, is a tried and tested game where molecules, mutation, and selection are linked on a board and students have fun playing with simple pieces and acting as “evolution masters”. The aim of this innovative educational tool is to help students to acquire knowledge on: gene expression (genetic code, transcription, translation); mutation; natural selection, and how these are interrelated.
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The materials needed for the game are simple and cheap:
- Dough, clay and/or plasticine (minimum 4 colors: blue, red, yellow, and green)
- Dices and pawns
- Cardboard cards
- Color markers/pencils
The elements of the game can be created by students in class or prepared in advance by the teacher. They are:
- The game board. Painted on a large card or paper (Fig. 1), it may be as imaginative and colorful as the participants want. The spaces contain events that may happen to a DNA molecule, conditions that a protein must accomplish to be “fitted”, and/or others. The start and end are 5' and 3' respectively. Figure 1 shows a game board containing the simplest elements. It may be much more elaborated and contain for example catastrophic events like spaces with “Climate crash” or “Resource extinction” (the player will be sent out of the game or have to start over), and positive moves like “Population expansion” (one extra DNA chain will be given to the fortunate player). In this simple version there are four different types of spaces in the board (Fig. 1): Neutral, Bridge, Selection and Evolution. In a Neutral space nothing happens. Bridge spaces (like in the game of the Goose or the game of Snakes and Ladders) connect different sections of the board. Selection spaces are marked with the acronym of an aminoacid and the player's protein should have this aminoacid to be fit and keep on playing. Evolution spaces are marked as E and indicate that the player must take an Evolution card (see below).
DNA and mRNA strands: made of dough/clay where toothpicks are inserted (Fig. 2). The clay strip symbolizes the phosphate-deoxyribose (or ribose if RNA) chain and the toothpicks represent the chemical bonds with the bases.
- Bases: small balls made of plasticine that will be attached to toothpick tops (Fig. 2). The bases are represented in different colors, which are similar to those that appear in real chromatograms of DNA sequences. Students have generally seen these chromatograms in movies and TV series such as CSI, Bones and others. Red is for thymine (T), blue for cytosine (C), yellow for guanine (G), and green for adenine (A). In RNA there is uracile (U) instead of the thymine and here we represent it in pink.
- tRNAs carrying aminoacids (Fig. 3): made of cardboard, each aminoacid is carried by the corresponding tRNAs according to the genetic code. The tRNA contains three bases (in the colors indicated above) that will match the mRNA triplets–and ultimately be identical of the DNA codons. The number of copies of each aminoacid is not the same. In Nature, some aminoacids (phenylalanine, valine, threonine, tryptophan, isoleucine, methionine, leucine, lysine, and histidine) cannot be synthesized de novo by humans (the players) and must be supplied in the diet. Since they are less easily obtained, only two copies of each essential aminoacid will be available in DNA Re-EvolutioN in contrast with 10 copies of any nonessential one.
- The Cards. Of cardboard, they indicate actions or events that will affect the molecules at play. They are called “Evolution cards”, affect DNA and represent mutations (Fig. 4). They exhibit the number of nucleotides to be added (indicated as + A, C. G or T), removed (- A, C, G, or T) or substituted (CG, AT and so on), from a DNA chain. A minimum of 30 cards with different indications should be prepared. 1/5 of them carry visibly marked the word “mutator” (explained below). Evolution cards are piled face down and should be shuffled before each game.
Figure 1. A prototype of board to play DNA Re-EvolutioN. The board contains an “evolutionary trail” or “pathway” formed by 60 correlative spaces, disposed at random for a good alternation of actions. Colors, draws and figures can be employed for decorating the board. We have shaped the trail as a big double helix of DNA. There are four different square types: Neutral, Bridge, Selection, and Evolution spaces. Neutral squares exhibit any symbol, picture or draw related with genetics. Each Bridge space (in orange in this model) is linked with other Bridge space by a schematic bridge. Selection spaces (in white) exhibit aminoacid acronyms. Finally, Evolution spaces (in green) are marked with an E.
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Figure 2. Nucleic acids and their nucleotides. DNA and mRNA strands can be modeled in any material (for example dough). The white string represents the phosphate-deoxyribose or phosphate-ribose chain and the toothpicks are the chemical bonds where the nitrogen bases will be attached. The colored balls represent nitrogen bases, as it follows: green is adenine, red is thymine, yellow is guanine and blue is cytosine. These colors parallel the standard colors of DNA chromatograms. In mRNA strands the uracil is represented in pink.
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Figure 3. tRNA pieces with aminoacids for the translation process at the end of the game. The pieces simulate tRNAs charged with the corresponding aminoacids and are employed to create the final protein. They exhibit a T-shape for students to remember their real structure.
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Figure 4. Mutations occurring during DNA Re-EvolutioN game. Players will find different possibilities of evolving by mutations: to add (Example 1), to take out (Example 2), or to change (Example 3) a nucleotide. Each one represents a type of mutation: (1) insertions, (2) deletions, (3) substitutions (transitions/transversions).
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In addition to the above described elements, a table containing the genetic code will be given to each player. Alternatively a big colored table can be prepared and placed nearby for everybody to consult it during the game.
Rules of Play
DNA Re-EvolutioN can be played individually or in small teams. Each player or team has two longitudinal pieces of clay with toothpicks (Fig. 2, right), a die, a pawn and a notebook or page for taking notes. The game starts making a short one-strand DNA chain on one clay strip. The player will pick up 21 bases (plasticine balls) of his/her choice and attach them to the toothpicks. Since one triplet of nucleotides codes for one aminoacid, the DNA strand will code for a protein of seven aminoacids, according to the genetic code. Students should “transcribe” its DNA chain into mRNA (Adenine matches with Uracil, Cytosine with Guanine) and construct a “mRNA chain” on the second clay strip. They should check the genetic code to be sure their mRNA really codes for seven aminoacids (if there is a stop codon in the middle the protein will be shorter). Then, they will translate the mRNA chain into aminoacids and write the aminoacid chain in the notebook.
When all the players have their nucleotide chains prepared they start moving along the board (Fig. 1). Players roll the die in turns and move their pawns on path spaces.
When a player lands on a Bridge, he/she must cross it to the connected Bridge space, moving forward or backward.
When a player arrives to a Selection space he/she checks if it is in his/her protein (in the notebook). If the player's protein does not contain such aminoacid, the player has to spend one turn without playing (simulating that he/she is not favored by natural selection).
When a player lands on an Evolution square he/she has to pick up one Evolution card. Evolution cards modify (= mutate) the DNA chains and the player follows the card's instructions modifying accordingly the own DNA chain: removing/adding/substituting the number and type of nucleotides indicated on the card. For more fun, some Evolution cards are marked as “mutator”. If the player picks one of those he/she will act as a “mutator” of other player's DNA chain following the card's instructions. Wise players will check the genetic code for executing card's instructions in the own DNA (trying to induce “synonymous” mutations i.e. without changing the aminoacid chain), and the opposite (nonsense or non-synonymous mutations) in other player's. During the play, DNA chains and the corresponding mRNAs and proteins will change depending on own and other players' Evolution cards.
The 3' end of the board path can only be entered by exact throw of the die, as in the Parcheese. If the throw is not exact, the player has to go back the extra amount of spaces in a throw.
When a player arrives to the end of the path will construct a “cardboard protein” from his/her definitive DNA chain, transcribing it into mRNA (as he/she did during the play) and translating it to a cardboard protein chain employing the small pieces that simulate tRNAs charged with aminoacids (Fig. 3). The player who arrives first will have all aminoacids available for his/her protein. Later-arriving players may miss scarcer essential aminoacids and their proteins remain incomplete.
The player with the longer protein wins the game.
Molecular Genetics and Evolutionary Concepts Learned with DNA Re-EvolutioN
For molecular genetics, DNA, mRNA, and tRNA structure and relationships are recalled while playing, as well as the processes of transcription and translation. The main types of mutational events and their synonymous or nonsynonymous character (from the genetic code) are also parts of the play. Students will understand—or recall- how changes in DNA affect the final protein product.
In the field of evolution, students will see how their DNA molecules change along the play: mutations are the material for evolution, and from mutations the functional product or phenotype (protein) may be altered or not. Not all phenotypes are equally fit, since in DNA Re-EvolutioN the longer the better for proteins (we strongly recommend to tell students that selection by protein length is just a rule of this game and not a reality). The role of the environment is represented by different number of tRNA-aminoacid copies: nutrient shortage is a factor of selection for many species.
Evaluation of DNA Re-EvolutioN
DNA Re-EvolutioN game was evaluated by students with different background in genetics. The game was played in the University of Oviedo within the course on Evolution and Biogeography of Marine Organisms (http://embc.marbef.org/index.asp?mod=cursusid=3823). This course is part of the International (formerly Erasmus Mundus) MSc in Marine Biodiversity and Conservation. Students from all continents participate in this program. We have tested the game in four different classes of 8, 9, 9, and 10 students each, from four consecutive cohorts (2009–2012): 36 students in total from 13 different countries. From their background in genetics, students were classed as 12 majors (at least 24 previous credits in genetics, molecular genetics, molecular evolution) and 24 nonmajors (Graduates in Biology or related sciences with less that 12 credits in genetics). All the students from each class played the same game (i.e., 8–10 players per game), in two-person teams whenever possible and one three-person team in the two uneven classes. In case of larger classes we would suggest to split them in groups of a maximum of ten students per game, for playing in pairs. Four or five teams of player pairs are a good number for dynamic and fun game.
The game was played for 1 h approximately. A questionnaire (Table 1) was given to students to be answered before playing as a pre-test, and again at the end of the game as a post-test. Fifteen minutes were allowed to respond the test in the two cases. Student's learning gain was assessed by the difference in the number of correct and complete answers between the pre- and post-tests.
Table 1. Questionnaire passed to students before and after playing DNA Re-EvolutioN (pre- and post-tests respectively).
|Define or explain briefly:|
|2) Silent mutation|
|3) Neutral mutation|
|6) Synonymous codon|
|9) Essential aminoacid|
The results were similar in the four cohorts, thus a cohort bias could be discarded. We have pooled all the cohorts for statistical analysis. In all the cases, players increased (a few maintained) the number of correct and complete responses after playing DNA Re-EvolutioN and no one got a lower mark (Fig. 5). The difference between pre- and post-tests was highly significant for both majors and non-majors (paired t-tests yielded t = 3.20 and 7.34 with p = 0.0047 and 0.0001, respectively). As expected, majors obtained better pre- and post-test results, but non-majors achieved greater learning gains (22% improvement in non-majors and 16% in majors), which makes the average difference of correct answers between majors and nonmajors smaller after playing (a difference between majors and nonmajors of 2.3 before playing and 0.9 after playing; see Fig. 5).
Figure 5. Evaluation Results. Pre- and post-test in majors (N = 12) and nonmajors (N = 24). Nonmajors (A) obtained an average of correct responses of 5.89 before and 8.11 after the play, while majors (B) yielded an average of 7.5 and 9.1 correct responses before and after the game respectively.
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Students were also asked to evaluate the game in a scale from 0 (not interesting at all) to 10 (very interesting and formative) and to leave comments. DNA Re-EvolutioN got excellent appraisals by both major and non-major audiences, obtaining a mean mark of 8.9. Most players (78%) asserted that DNA Re-EvolutioN is fun, useful and can be played easily, 97% of them declared their willingness to play it again, and 93% participants would recommend it for explaining the basis of molecular genetics.
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Genetics laboratory teaching can be limited by several factors like preparation time and cost . Facing the lack of resources of some institutions and high schools, DNA Re-EvolutioN offers a possibility to teach main concepts in molecular genetics in a nonexpensive dynamic session. Besides its low cost, the advantage of this activity based on playing as a teaching resource is its interactive quality that creates a stimulating learning environment .
The main goal of this game is to understand how changes in DNA can affect the organisms and their evolution. Every step in the play has been based on key theoretical concepts and students will learn about molecular genetics (structure of DNA, transcription, translation, etc.) while they are having an entertaining time. In DNA Re-EvolutioN mutations happen at random and natural selection favors (or not) some changes, as it happen in Nature. DNA Re-EvolutioN integrates many concepts in a short time of game—approximately 1 h. Promotion of simulations and games is recommended in Higher Education ; learning happens naturally in a different, didactic and entertaining way far from typical lectures. Indeed, teachers should explain in depth these concepts in theory lectures, adapting the explanations to the educational level of the students.
In conclusion, DNA Re-EvolutioN is a flexible and feasible game for majors and non-majors to learn and enjoy molecular evolution. It can be programmed for one lesson within a variety of courses, from Evolutionary Biology to Molecular Genetics, and adapted to different educational levels.