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nonpolar polar basic acidic (stop codon) 2nd base U U C 1st base A A G UUU (Phe/F) Phenylalanine UCU (Ser/S) Serine UAU (Tyr/Y) Tyrosine UGU (Cys/C) Cysteine UUC (Phe/F) Phenylalanine UCC (Ser/S) Serine UAC (Tyr/Y) Tyrosine UGC (Cys/C) Cysteine UUA (Leu/L) Leucine UCA (Ser/S) Serine UAA Stop (Ochre) UGA Stop (Opal) UUG (Leu/L) Leucine UCG (Ser/S) Serine UAG Stop (Amber) UGG (Trp/W) Tryptophan CUU (Leu/L) Leucine CCU (Pro/P) Proline CAU (His/H) Histidine CGU (Arg/R) Arginine CUC (Leu/L) Leucine CCC (Pro/P) Proline CAC (His/H) Histidine CGC (Arg/R) Arginine CUA (Leu/L) Leucine CCA (Pro/P) Proline CAA (Gln/Q) Glutamine CGA (Arg/R) Arginine CUG (Leu/L) Leucine CCG (Pro/P) Proline CAG (Gln/Q) Glutamine CGG (Arg/R) Arginine AUU (Ile/I) Isoleucine ACU (Thr/T) Threonine AAU (Asn/N) Asparagine AGU (Ser/S) Serine AUC (Ile/I) Isoleucine ACC (Thr/T) Threonine AAC (Asn/N) Asparagine AGC (Ser/S) Serine (Ile/I) Isoleucine ACA (Thr/T) Threonine AAA (Lys/K) Lysine AGA (Arg/R) Arginine (Met/M) Methionine ACG (Thr/T) Threonine AAG (Lys/K) Lysine AGG (Arg/R) Arginine GUU (Val/V) Valine GCU (Ala/A) Alanine GAU (Asp/D) Aspartic acid GGU (Gly/G) Glycine GUC (Val/V) Valine GCC (Ala/A) Alanine GAC (Asp/D) Aspartic acid GGC (Gly/G) Glycine GUA (Val/V) Valine GCA (Ala/A) Alanine GAA (Glu/E) Glutamic acid GGA (Gly/G) Glycine GUG (Val/V) Valine GCG (Ala/A) Alanine GAG (Glu/E) Glutamic acid GGG (Gly/G) Glycine AUA AUG G C [A] [A] The codon AUG both codes for methionine and serves as an initiation site: the first AUG in an mRNA's coding region is where translation into protein begins. [Show title “A 3D representation of the genetic code” and the skinned version of the code, hold for 3 seconds, then remove the title and allow the skinned version to slowly rotate.] The genetic code can mean different things to different people. Some people take it to mean all of an organism’s DNA instructions. Other people would argue that the term “genome” is a better way to describe the set of DNA instructions. Most scientists would say that the genetic code is the code that takes DNA information and converts it to protein information. So, we will use the term “genetic code” to describe this systematic conversion of information. In other words, we’ll use it to describe the code that takes information in the DNA and RNA language of four letters and translates that information into related information that is spelled out in the 20 letters of the protein language. Ok, so now that we’re clear on what we mean when we say “genetic code”, what are some ways to visualize and understand this code? The traditional visualization of the code is a table like this one, [switch to the “GeneticCodeTable.png” image] which you can find on Wikipedia. As you can see, this table helps a person see how the RNA letters U, C, A and G, [if possible, bring in the four png images and put them in a row under the CodonTable. If this is to time-intensive for the $100 version, please don’t do this]. which can be arranged into 64 different 3-letter words called codons, are matched up with the 20 letters of the protein language. Unfortunately, there are many features of the genetic code that this table does not adequately show us. For example, this table doesn’t give us a good idea of how one codon can mutate to another codon, which is the cause of some diseases such as Sickle Cell Anemia. [switch back to the rotating skinned version of the code] In our animation, we show a 3-dimensional visualization of the genetic code. To create this visualization, we start with four rods that stick out of a central ball. [remove skinned version and replace with the purple ball and four rods, slowly oscillating 30 degrees left and right over and over] These rods represent the four letters of RNA, which are nearly identical to the four letters of DNA. In our visualization, the blue rod pointing up represents the letter A. As you may have learned, A forms a pair with the letter T in DNA, but in RNA it forms a pair with the letter U, which is nearly identical in shape and chemical formula as T. In our visualization, the letter U is represented by the red rod, which points to the rear of our 3D model. The other two rods represent G and C, with G in black going to the left and C in white going to the right. Now, this first group of four rods represents the first letter in the three letter words called codons. As we build our visualization, we must add two more sets of rods, so that we can show all three codon letters in our 3D model. Ok. So, let’s add the second set. There we go… [add the second set of rods and the silver balls] As you may have noticed, this second set of rods is much longer than the first set. That’s because the second letter of each codon word gives us the most information about what kind of protein letter it will ultimately specify. In the English language, we know that some parts of a word are more useful to our brains when it comes to word recognition. Usually the first and last letters of an English word are most useful. But in codon words it’s the opposite. The first and (especially) the last letter of each three-letter word are the least informative. So, in our 3D model, we’ve made these letters smaller than the middle letter, as can be seen when we add the final set of rods (here they are) [add the third set of rods and the green balls, with the whole skeleton still oscillating slowly back and forth] which represent the last letter of the three-letter word and are therefore the shortest set of rods. If you took the time to count these short rods, you’d find that there are 64 of them. That’s because each of the first four rods had four long rods sprouting from their tips, for a total of 16 long rods, since 4 times 4 is 16. Likewise, each of the 16 long rods have four tiny rods sprouting from their tips for a total of 64 tiny rods, since 16 times 4 is 64. The 64 short rods tell us that there are 64 ways to put the 4 letters into 3-letter words. Now, since we are trying to go from the RNA or DNA language of 4 letters to the protein language of 20 letters, we had no choice but to use three letter RNA or DNA words. 2-letter words would have been too short because they would have only given us 16 possibilities. But now that we have 64 possibilities, we have more than we need. Does this mean that we should use up 20 of those 64 words and leave the other 44 as “nonsense” words that have no meaning? Well that’s what Francis Crick, the co-discoverer of DNA’s structure thought that that’s what we should do. But thankfully, Nature is a lot smarter than Francis Crick! Instead of those 44 words being mere nonsense, they are used as backup codes for the protein letters. Just like the word cap and the word hat, in the right context, mean the same thing, so also the RNA word, for example, AAA means the same as the RNA word AAG. Both words mean the letter “K” in the protein alphabet, which happens to stand for the amino acid lysine. The beauty of this system of backup codes can be seen as we look at how codons can mutate to other codons. [Do the three mutation animations as needed by the script] In the following animation, we see how the codon AAA can mutate to GAA, or to AGA, or to AAG. Obviously, these three mutations are not the only mutations that can happen to AAA. It could have mutated by replacing one of its A’s with a C or U so that, if you count them all together, there are 9 ways that AAA can change by what is called a single point mutation, which is the kind of mutation that leads to Sickle Cell Anemia, for example. But with the A to G changes that we are about to show you, it will give you the general idea of how one codon can change to another codon by a point mutation. So, let’s look at the first mutation example: the AAA going to the GAA. In our 3D model, we see that the rod that sticks out of the central purple ball is the one that rotates into a new position. The result is that the tiny rod that used to be at the very top of our model has now moved down and to the left. This tiny rod no longer is the end of the word AAA, it is now the end of the word GAA. In the second mutation example, we see the drastic bending of the second rod, which takes the AAA codon to the AGA codon. Again, your eyes should follow the tiny rod that starts at the top of the model and see that it moves even further down and to the left compared to the first mutation. In the third mutation example, we see a relatively small change. The tiny rod simply bends down to a new position such that AAA becomes AAG. This third mutation example shows us the power of the backup code system. As I mentioned earlier, AAA and AAG code for the same thing in the protein alphabet. So, if there is an A to G mutation in the third letter of the AAA codon, it doesn’t affect the meaning of the message. In other words, the genetic code is extremely robust with respect to mutation errors. And thank goodness! Otherwise many more of us would be affected by debilitating genetic diseases.