Evolution of the Genetic
Code
Adi Stern
30/3/05
1
Outline
1.
2.
3.
4.
Introduction – the translation
mechanism
Cracking the code
Genetic code(s)
The 3 theories of evolution
2
Introduction - translation
3
tRNA

Matches amino acids
to codons in mRNA
4
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

5
tRNA

61 codons → < 61 different tRNAs:
human: 48 different tRNAs (anticodons)
bacteria: 31 different tRNAs (anticodons)
BACTERIA
EUKARYOTES
Wobble (codon
base 3)
(anticodon base 1)
Wobble (codon
base 3)
(anticodon base 1)
U
C
A
G
A,G or I
G or I
U or I
C or U
U
C
A
G
G or I
G or I
U
C
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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)
8
The Diamond code (Gamow,1954)
Problems:
(1) overlapping code, restricts aa neighbours.
9
(2) translation in ctyoplasm
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
ABA ABB ACA BCC

aa1
aa2
?
“The most genius theory proved wrong…”
aa3
aa4
Does not exist!
10
Cracked!
A Cell-free system was devised
in 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)

13
But … there isn’t only 1 code, but 16!
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 The code can evolve.
  Codon assignments are non-random

15
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Adaptation
17
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
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Standard genetic code
BUT …


This works when the criteria is:
- polarity
- PAM distance
But it doesn’t 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)
AT pressure
reduced
2.
TGG (Trp),
AT pressure TGA → disappears,
replaced for instance
by TAA (Stop)
4.
TGA reappears,
unrecognized
3.
release factor (TGA)
disappears (no
selective pressure)
5.
tRNA (TGG) for Trp
duplicates, and mutates to
recognize TGA. Now TGA
codes for Trp
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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.
 Theory:
First base – similar biosynthetic pathway
Second 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-tRNASynthetases 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.

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