2. Time scale for the origin of life
The origin of the genetic code is the end of the RNA World
What preceded RNA?
Another polymer?
Metabolism only?
Dating of
rocks and
meteorites
Last ocean-
vaporizing impact.
Lunar craters
Isotopic evidence
for life
Microfossil evidence
Stromatolites.
Phylogenetic methods
(divergence after LUCA)
3. History
Genetic codons Discovered by Marshall
Nirenberg, Heinrich Matthaei, Philip Leder and
Har Govind Khorana in 1968.
Nirenberg and Khorana got the Nobel prize.
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4. Definition
Genetic code is a triplet of nucleotides that
codes a specific amino acid.
Ex. AUG-met
UUU-Phe
The amino acids encoded
by all 64 possible codons
were determined.
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5. The Genetic Code
DNA is a genetic martial.
the genetic code required determining how 4
nucleotides (A, T, G, C) could encode more
than 20 amino acids.
Francis Crick and Sydney Brenner determined
that the DNA is read in sets of 3 nucleotides
for each amino acid.
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6. Evidence for the Triplet Code
• How Many RNA Bases Specify One amino acid code;
20 amino acids code?
• If a codon consisted of only one mRNA base?
• Two base, for example, provides only 16 unique code
words (42). Not enough..!
• A triplet code yields 64 words (43) and therefore is
sufficient for the 20 amino acids.
• A four-letter code (44), which would specify 256
words.
Theory
7. THE GENETIC CODE
Each codon consists of three bases (triplet).
There are 64 codons.
They are all written in the 5' to 3' direction.
61 codons code for amino acids. The other
three (UAA, UGA, UAG) are stop codons (or
nonsense codons) that terminate translation.
There is one start codon (initiation codon),
AUG, coding for methionine. Protein
synthesis begins with methionine (Met) in
eukaryotes, and formylmethionine (fmet) in
prokaryotes.
The code is unambiguous.
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8. More than one codon can specify a single amino acid.
All amino acids, except Met and tryptophan (Trp), have
more than one codon.
For those amino acids having more than one codon, the
first two bases in the codon are usually the same. The
base in the third position often varies.
The code is almost universal (same in all organisms).
Some minor exceptions to this occur in mitochondria and
some organisms.
The code is commaless (contiguous).
There are no spacers or "commas" between codons on an
mRNA.
Neighboring codons on a message are non-overlapping.
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9. The Genetic Code
reading frame: the series of nucleotides read in sets of 3
(codon)
only 1 reading frame is correct for encoding the correct
sequence of amino acids
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UUC GAG
UUU
AUG
UCG AAU
U UCU CGA UGU UUG AGA
UU
AU
CUC GAU GUU UGA GAA U
Reading frame 1
Reading frame 2
Reading frame 3
11. Types of codons
stop codons: 3 codons (UAA, UGA, UAG) in the genetic
code used to terminate translation
start codon: the codon (AUG) used to signify the start of
translation
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12. Characteristics of the Genetic Code
Unambiguous
Each codon specifies a particular amino acid, the codon ACG
codes for the amino acid threonine, and only threonine.
Non overlapping
This means that successive triplets are read in order. Each
nucleotide is part of only one triplet codon.
Commaless which mean there is no punctuation
between two codons
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14. The Wobble Hypothesis
The first two bases of the codon make normal
(canonical) H-bond pairs with the 2nd and 3rd bases
of the anticodon
At the remaining position, less stringent rules apply
and non-canonical pairing may occur
The rules: first base U can recognize A or G, first
base G can recognize U or C, and first base I can
recognize U, C or A (I comes from deamination of A)
Advantage of wobble: dissociation of tRNA from
mRNA is faster and protein synthesis too
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15. Wobble hypothesis
• Crick postulated the wobble hypothesis.
• He predicted that the initial two ribonucleotides of
triplet codes are often more critical than the third
member in attracting the correct tRNA.
• He hypothesized that hydrogen bonding at the third
position of the codon-anticodon interaction would be
less spatially constrained.
• In addition, it may also need not to adhere strictly to
the base-pairing rules.
16. Wobble hypothesis
• 61 different tRNAs could theoretically exist, one for
each codon that specifies an amino acid, however only
49 different genes encode tRNAs.
• This is because the same type of tRNA can detect
synonymous codons that differ only in whether the
wobble (third) position is U or C.
• The same type of tRNA, for example, binds to both UUU
and UUC codons, which specify the amino acid
phenylalanine.
• Synonymous codons ending in A or G use different
tRNAs
18. Conclusion:
It is a triplet code.
– Each three-nucleotide codon in the mRNA specifies one amino acid
• It is comma free.
– mRNA is read three bases at a time without skipping any bases.
• It is non-overlapping/non-ambiguous.
• It is almost universal.
– In nearly all organisms, most codons have the same amino acid
meaning.
– Of 20 amino acids, 18 are encoded by 2 or more codons.
• The code has start and stop signals.
– AUG is the usual start signal and defines the open reading frame.
• Stop signals are codons with no corresponding tRNA
– the nonsense or chain-terminating codons.
– generally three stop codons: UAG, UAA, and UGA.
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19. In the film Jurassic Park, which is about cloned dinosaurs, a
cartoon character named Mr. DNA talks about the billions of
genetic codes in DNA.
Why is this statement incorrect?
A code of 3 nucleotides could code for a maximum of 43
= 64 amino acids.
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