Evolution of the Genetic Code

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Evolution of the Genetic Code

• Adi Stern
• 30/3/05

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Outline

1. Introduction the translation mechanism
2. Cracking the code
3. Genetic code(s)
4. The 3 theories of evolution

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Introduction - translation
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tRNA

• Matches amino acids to codons in mRNA

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Aminoacyl-tRNA synthetase

• Attach amino acids to tRNA
• Most cells 20 aminoacyl synthetases
• Bacteria less than 20, some incorrectly
  attached tRNAs are modified
• High-accuracy defining stage

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tRNA

• 61 codons ? lt 61 different tRNAshuman 48
  different tRNAs (anticodons)bacteria 31
  different tRNAs (anticodons)

BACTERIA
EUKARYOTES
(anticodon base 1) Wobble (codon base 3)
G or I U
G or I C
U A
C G
(anticodon base 1) Wobble (codon base 3)
A,G or I U
G or I C
U or I A
C or U G
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CRACKING THE CODE

• 1953 DNA structure (Watson and Crick)
• 1961 the genetic code (Matthaei and Nirenberg)

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in between

• George Gamow a Russian physicist, is excited by
  the double helix
• The RNA tie club

Crick (Tyrosine)
Watson (Proline)
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The Diamond code (Gamow,1954)
Problems(1) overlapping code, restricts aa
neighbours.(2) translation in ctyoplasm
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Comaless code (Crick, 1958)

• No commas (proved correct)
• Only 20 of 64 codons are meaningful all other
  are skipped.
• No frameshift!
• ? a codon such as AAA is meaningless

The most genius theory proved wrong
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Cracked!

• A Cell-free system was devisedin which
  UUUUUUUUUUUU was translated (FFFFFFF)
  CCCCCCCCCCCC was translated(PPPPPPP)and so
  on
• Almost disappointing

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The standard genetic code
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The Universal Genetic Code?

• Found in all organisms
• Change in the genetic code would affect all
  coding proteins ? lethal.
• The frozen accident (Crick, 1968)

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But there isnt only 1 code, but 16!
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• ? The code can evolve.
• ? Codon assignments are non-random

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(No Transcript)
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Adaptation
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• Reduces the effect of translation error
• Reduces the effect of point mutation
• but these are chemical considerations

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Code optimality

• Compare the code(s) with random alternatives

Standard genetic code
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BUT

• This works when the criteria is- polarity- PAM
  distance
• But it doesnt work with- size
• there is a lot of debate on the validness of
  these methods (e.g. DeGulio 2000)
• HOW IS CHANGE POSSIBLE?

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Codon Capture

• The codon capture theory (Osawa-Jukes
  1988)Following GC content pressure on the
  genome, tRNAs disappear and reappear with a
  different recognition.

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Codon-Capture Model

• Supposed model in Mycoplasma capricolum

1. TGG (Trp), TGA (Stop)
2. TGG (Trp), TGA ? disappears, replaced for
instance by TAA (Stop)
3. release factor (TGA) disappears (no selective
pressure)
AT pressure
4. TGA reappears, unrecognized
5. tRNA (TGG) for Trp duplicates, and mutates to
recognize TGA. Now TGA codes for Trp
AT pressure reduced
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Evidence in favour

• In Mycoplasma capricolum, tRNA (TGG) and tRNA
  (TGA) are on the same operon.
• In related bacteria the codon TGG has entirely
  disappeared(replaced entirely by TGA)

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The ambiguous intermediate

• Codons did not disappear tRNAs which are
  ambiguous, led to fixation of one tRNA codon in
  one species an to another in another species
• Supporting evidence E.Coli UAG translates to
  stop, Trp or selenocysteine.
• Replacements of all codons by another a.a. are
  not necessarily lethal!Experiment partial
  replacement of Ile by Cys in E.Coli resulted in
  only low loss in fitness! (Doring and Marliere,
  1998)

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Genome streamlining hypothesis

• Pressure to minimize the genome of mitochondria
  (or other) obligatory parasites leads to
  reassignment of codons.
• Transfer of genes to nuclear genomes ? less
  constraint on the mitochondria genome.

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History a slowly growing code

• Initial, limited set of amino acids.
• Newly introduced amino acids according to similar
  biosynthetic path.
• New amino acids did not make drastic change in
  the protein.
• TheoryFirst base similar biosynthetic
  pathwaySecond base similar aa properties

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tRNA, aa-tRNA-Synthetase phylogenies

• aa-tRNA-Synthetases phylogeny supports the
  biosynthetic theory
• Phylogenies of tRNA and aa-tRNA-Synthetases are
  non-congruent
• So maybe all this happened within the Last
  Common Ancestor of all organisms

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Summary-change in genetic code

• Primordial code expansion of code from few to 20
  a.a.s
• tRNA and aa-tRNA-Synthetases are invented ? this
  enables codon swapping and code optimization
• Ambiguity enables change
• Most of these changes in relatively simple
  organisms.