Download Paper Notes: The Genetic Code – More than Just a Table

Paper Notes: The
Genetic Code –
More than Just a Table
• Two major sections
– Review of the literature
• ...of general interest
– New contribution
• ...cool to see
• ...of less general interest
Let us focus on the general interest material
What is the Genetic Code?
What is the Genetic Code?
• What the codon table says (19 of 27 refs.)
– That's over 2/3 sources being wrong!
• Instructions for protein synthesis (3/27)
– That's another 11% wrong!
• Mechanism for storing genetic info (2/27)
– I can live with this
• DNA sequences (2/27)
– Not sure...what do you think?
• Other (1/27)
• So, 81+% of Web sources are flatly wrong
– (This does not necessarily mean 19% are right)
What's Wrong with the Codon Table
• Yes, people think it is more than it is
– But is anything else wrong with it?
• The standard codes are not reliable
– UGA also codes for selenocysteine
– UAG also codes for pyrrolysine
– AUG also codes for methionine
• These 3 are coded deterministically, but the
codon table does not determine even AUG
What's Wrong with the Codon Table
• Yes, people think it is more than it is
– But is anything else wrong with it?
• The standard codes are not reliable
– UGA also codes for
• selenocysteine
– UAG also codes for
• pyrrolysine
– AUG also codes for
• methionine
• These 3 are coded deterministically, but the
codon table does not determine even AUG
Some Amino Acid Codes
are Ambiguous
• CUG can be either serine or leucine
– In yeast Candida
• AUG codes for methionine
– Animals can accidentally
incorporate selenomethionine
• Some codons code differently
in different species
– Sometimes mitochondrial
code differs from nuclear
• (Same species - why?)
Some Amino Acid Codes
are Ambiguous
• AGG is a notable case
– Can mean arginine, serine, glycine, or STOP
• (depends on species)
• Worse yet: it can be
unassigned
• What might that mean?
Source:
http://2011.igem.org/wiki/ima
ges/2/26/11SJTU_Rare_03.jpg
Fixing the Codon Table
• How might the table be fixed?
Source:
http://plan
tandsoil.u
nl.edu/cro
ptechnolo
gy2005/Us
erFiles/Im
age/siteIm
ages/Tabl
e1gif.gif
This won't fix everything
• Are some codons synonymous?
• Is this information provided by the codon table?
What About “Partial Synonymity”?
• Third position tends not to distinguish between
amino acids as much as first two
What About “Partial Synonymity”?
•
• Similar codons tend to code for physicochemically similar amino acids
– Why?
•
•
•
What About “Partial Synonymity”?
•
•
• If position 2 in a triplet is U, amino acid is
hydrophobic
•
•
What About “Partial Synonymity”?
•
•
•
• Heavier amino acids tend to have fewer codons
•
What About “Partial Synonymity”?
•
•
•
•
• Frequent amino acids tend to have more codons
Annotating the Codon Table
Won't Help With:
• Cross-species variation in
– Codon usage bias
• Arginine is CGC:
– 33% of the time in fruit flies
– 18% of the time in humans
• What about the other 82%?
• Why is there codon usage bias?
• Successful gene implantation can require using
the right codon, not just any of the right n
– Green Fluorescent Protein
Annotating the Codon Table
Won't Help With:
• Different codons for the same amino acid:
– can take different amounts of time to translate
• Why?
• Different translation times can affect
– Amount of protein made
– Protein folding
» That can make a big difference
» Example: E. coli
Annotating the Codon Table
Won't Help With:
• Codon table does not contain angle information
– A table of codon pairs would
– 6 base pairs define a natural angle!
• (3 do not)
• That's pretty blatant...
– A table of angles would be based on
• 6-tuples, not triplets!
• How many 6-tuples are there?
• What might such a table look like?
Annotating the Codon Table
Won't Help With:
• Codons “buffer” against mistranslations
– The codon table is a “frozen accident”
• ...said Francis Crick
– But it's not!
Why It's Not
• Here's why
– How many codons can a given codon change
into with one (1) base change?
– The average amino acid can mutate to 1/3 of
the others with 1 base change
– These tend to have similar physico-chemical
properties
• Why?