The Gene Expression Game

by: Dr. Terry L. Helser, Associate Professor of Chemistry
227 Physical Sciences Building, Oneonta, NY 13820-4015
Phone: (607)436-3518 or Email to:
DNA Strand

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The "secret of life," if there is but one, is the ability of the information encoded in the base sequence of DNA to be transcribed into an mRNA and translated into a polypeptide chain, forming a functional protein - and to do so always in a controlled manner. These processes are the essence of gene expression and of life itself at the molecular level. A great deal is now known about the mechanisms used to express genetic information, and in particular how this is controlled.

For example, a normal E. coli cell can utilize the sugar, lactose, when it is supplied in place of glucose. The ability to split lactose, a disaccharide, into the monosaccharides glucose and galactose depends on a specific enzyme, ß-galactosidase, which normal cells can synthesize. However, in the absence of lactose, this enzyme is not needed, and is not made. It would be a waste of energy for the cell to produce any protein it does not require. Thus, the enzyme is made only when lactose, the substrate for the enzyme, is supplied. Such a genetic control is called induction.

In addition, glucose can prevent the synthesis of ß-galactosidase, as well as other enzymes for alternate energy sources, even in the presence of lactose (the inducer). Glucose, the most efficient energy source for cells, is always used first. This regulatory system is called "catabolite repression," since it is a product (catabolite) of glucose which actually controls the system.

The purpose of the gene expression game you are about to play is to increase your knowledge and understanding of the steps involved in gene expression and its controls, while having some fun. It will be to your advantage to study the models given in your text book for induction and catabolite repression before attempting to play. Of course, you can allow your opponents to teach you the finer points of gene expression, if you so desire! To the game!

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Object: To express your gene before your opponents can complete theirs, and thus by more fit to survive natural selection.

Rules: You will play the option where all organisms (players) express the lac operon, so deal one "THE LAC OPERON" card to each player.

  1. Give each organism a "Repairase" card. It may use this card only once to repair a block, provided the organism correctly explains how the block is being repaired. If it fails to do so, the organism loses one turn. (This is the only card that is not a real part of gene expression in E. coli.)
  2. The Hfr organism (male), if present, deals 10 cards face down to each player (3 or 4 players/deck) and two cards for each organism face-up in the center as a discard set. The deck is placed face down in the center.
  3. Starting with the E. coli to the left of the Hfr, each organism, in turn, lays one card down directly in front of it to express its gene, on a competitor's card to block its expression, or in the discard area. It then picks any card from the discard area, or one card off the top of the deck, to keep 10 cards in its hand. An organism who fails to replenish its hand may be required by its competitors to play with the number it has. Selection is ruthless. The order of playing a card and then drawing a replacement is essential to prevent players from picking blocking or block removal cards from the discard area and playing them immediately. You must plan ahead!
  4. An organism survives natural selection (wins) by being the first to express its gene in a correct order by aligning the 12 cards (steps) needed to produce active ß-galactosidase from left to right in front of it.
If you are to succeed in an uncertain world, you must be versatile enough to overcome any obstacles forced upon you by competing organisms, i.e.-
  1. If you omit a step, or place it out of order, and a competing organism can prove this (Remember, however, that some steps may not have to be played in the order given on the next page!), you suffer degradative turnover of all steps beyond the error. Return all cards to your hand and then discard until you hold only 10. If the challenging organism is wrong, it loses a turn for wasting energy needlessly.
  2. A competitor may block your pathway by laying a blocking card only on the last card you played, and only where the block would be effective. Inappropriate blocks may be ignored and your competitor loses its turn, since it wasted energy blocking you. Appropriate blocks must be corrected with either a specific repair card played on the blocking card, or by Repairase (see 1. above). Unfortunately, your competitors may find it advantageous to place multiple blocks on the same step. Competition is sometimes relentless!
  3. If you are unfortunate enough to suffer turnover of a segment of your pathway containing a Repairase or Puromycin card, it is removed from play. Blocking and block repair cards may be retained as part of the 10 cards in your hand, or discarded (where your competitors can get them).
Any questions? Express those operons, and may the most "fit" organism survive!

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Below are the texts of the cards you will use in THE GENE EXPRESSION GAME.
The GENE CARD tells you who and where you are:
You are an E. coli who drops into milk. 
Express the lac operon to make the enzymes needed to use lactose.
The following game cards are given in only one of several possible orders.
Active repressor binds to the operator gene, stopping expression. 
Amino acids, linked to tRNAs (AA-tRNAs), are ordered into protein by the ribosome. 
Catabolite Activator Protein/ cAMP complex binds to the promoter allowing transcription. 
 EF-G and GTP drive the ribosome along the mRNA. 
Lactose binds to the repressor, inactivating it. The operator is open. 
Release Factors (R1 or 2) stop protein synthesis. 
RNA polymerase/ sigma (s) factor bind to the promoter starting RNA synthesis. 
Proteases trim the N-terminal end of the protein.
RNA polymerase links nucleotide triphosphates in a 5' to 3' direction. 
Rho (r) factor stops mRNA synthesis. All components recycle. 
The 30S subunit complex binds to the mRNA and the 50S subunit joins. Protein synthesis begins. 
Active ß-galactosidase is hydrolyzing lactose. 
(Ooops! You just were PASTEURIZED!) 

The following are the legends used in paired blocking (red) and block-removal (green) cards:

The lac repressor is a mutant. 
Lactose can't induce operon synthesis. 
You have an operator constitutive mutation. 
mRNA Repressors can't bind to your operator gene. Continue. 
The milk contains glucose. cAMP disappears, inactivating CAP. RNA polymerase can't recognize the promoter. 
The glucose has been used. cAMP increases, activating CAP. Catabolite repression is reversed. 
A Streptomyces competitor is producing rifamycin. It binds to RNApase, blocking the initiation of transcription. 
You have mutated to rifr. Your RNA cannot 
bind rifamycin. Continue transcription. 
Chloramphenicol has inhibited your 50S subunit peptidyl transferase. Translation is frozen. 
Cows are fed this drug, causing the spread of Resistance Transfer Factors. You received one and are now immune to Chl. Continue Translation. 
The following legends are not for paired cards:
The AA-tRNA analog, puromycin, terminates protein synthesis. 
Turnover removes all evidence of translation. 
State how your defect is to be corrected, and
continue expressing your operon. 
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  Last Modified on 12/05/2008

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