Deciphering the Genetic Code

What is code?

• Representation of information
• Allows transfering and storing information

Examples

• Morse code

• Braille

• Computers

• DNA

What do these types of code have in common?

• All have some kind of alphabet
• Different combinations of letters also have different meanings
• Tea means something different from eat
• Our alphabet is a code for the sounds we make when speaking
• Many codes have different levels
  
• Above examples have some small set of basic characters (0/1, long/short)
  
• The also have a larger set of combinations of the basic characters
• Examples
• Morse
• short - long signal
• Combined in variable length groups (1 to 5), separated by a pause
• . stands for an "E"
• - for a "T"
  
• .- for an "A"
• Braille
• elevated - not elevated dot
• Combined in groups of 6
  
• Computer
  
• voltage high - low
  
• Correspond to 0 and 1
• Combined in groups of 8 (byte)
  
• DNA
• 4 types of molecules (A, C, G, T)
• Combined in sets of 3 (codon)
• If you are interested in codes in general ask your parents to give you the following book for your next birthday or for Christmas:
• Charles Petzold, "Code: The Hidden Language of Computer Hardware and Software," Microsoft Press, 2000.
  

How about the genetic code?

• Only 4 different pieces
• Adenine (A)
• Thymine (T)
• Guanine (G)
• Cytosine (C)
• Called nucleotides
  
• Chemical structure interesting for chemists but irrelevant for many aspects of code
• If we read along one of the sides we get text
• ATGTAAGCCATA ...

What does the text stand for?

• Normally letters stand for sounds
• Certainly not the case here
• Blueprint of life
• What is life?

What are aspects of life?

• We breathe and eat (take up energy)
  
• Run and keep warm (use energy)
  

What happens to air and food in our body?

• Oxygen and carbohydrates are converted to water and carbon dioxide and energy is released
  
• Similar to a candle flame
  
• Do we have little candles burning in our bodies?
• No, we have molecules that allow a similar process to happen at body temperature
• What are those molecules?
• Enzymes
• Special type of protein

Proteins

• Proteins are not just food
• Involved in most chemical reactions in our body
  
• Make up hair and nails
• Increase or decrease production of other proteins
  

What is the relationship between proteins and genes?

• Translation
• This is the biological term
• Matches what we expect for code
• Combinations of letters are translated
• Combinations of 3 DNA building blocks make one protein building block (amino acid)
• 20 different protein building blocks
  

Translation table

Translation example

Special codons

• Start codon
• ATG
  
• Stop codons
• TAA
• TAG
• TGA
  

Start / stop codon example

• In the following sequence, look for
  
• start codongs: ATG
• stop codons: TAA, TAG, TGA
  
• Find the gene, i.e. the longest stretch between start and stop codon
• Note that there are 3 ways of reading the sequence
• Note the one example of a STOP codon that is given already
  

How do we find a gene?

• Look for a start codon?
• We don't know in which of the three rows to look
  
• Happen accidentally, on average, every 64 letters
• Look for a stop codon?
• Happen even 3 times as often (every 21 letters)
  
• Look for absence of a stop codon!
• Question: in which of the three rows did you find the longest stretch without stop codon?
  

How do proteins work?

• Take a certain shape
• Shape determines how they bind with small molecules

Protein images

• Excercise
• Check Google for protein images
• Searching for protein tertiary structure
• Searching for protein folding

How do we find the shape?

• Experiments
• X-ray radiation
• Once we know some, we look for similarity in sequence
  
• Simple model
• Some protein building blocks (amino acids) like water (P)
  
• Some don't (H)

Protein structure example

• Draw Tic-tac-toe field

• Take the following protein
• H-H-P-P-P-P-H-H-P
• Place the protein on the grid such that each square is filled with one building block, and neighboring blocks are on neighboring squares
• Try to bring the Hs together on neighboring squares
  
• For example

• In this example there are two pairs of neighbors of Hs
  
• But you always have those, why?
  
• Each time you have Hs as neighbors you get one point
• Who gets the most points?

Protein structures online

• Go to http://www.rcsb.org/pdb/searchlite.html
• Type in "kinase"
• Click on any of the results
  
• Click on "View Structure"
• Scroll down and under Java click on QuickPDB
• Rotate by dragging

• You can also search Google Images for protein structure
  

Protein translation and subsequence search

• Some related work has been done in the summer 2004 by Governor School Student Ryan Carlsrud
• Check out
• http://www.cs.ndsu.nodak.edu/~adenton/GovernorSchool/RyanCarlsrud/GeneAnalysis.html
• Warning:  You may have to delete leading blanks
  
• Try the translation example

• Hit the Protein button
• Try searching for start and stop codons in the example sequence
  

Challenge

• I have no program that solves the protein structure prediction problem. 
  
• But I am offering you the following prize
  
• If you are the first from this group to write a program in any programming language that completes the following task (before finishing high school) I will contribute $30 to one or more books of somewhat related content.
• Many programming langages will serve this task
  
• Your program should have an input window that takes a string of Ps and Hs
• Based on the number of Ps and Hs an appropriately sized grid should be constructed
• You should calculate an optimal layout of the Ps and Ns on that layout, i.e., one that maximizes the number of H H neighbors.
  
• You should display that layout (can be done using text as in the above example)
• If you would like suggestions on how to get started please feel free to e-mail me at anne.denton@ndsu.edu