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chapter 25
RNA and Protein Synthesis
T A B L E 2 5 -2
“Universal” Genetic Code*
First
Position
(5' end)
Second Position
Third
Position
(3' end)
U
C
A
G
U
Phe
Ser
Tyr
Cys
U
Phe
Ser
Tyr
Cys
c
Leu
Ser
Stop
Stop
A
Leu
Ser
Stop
Trp
G
c
Leu
Pro
His
Arg
U
Leu
Pro
His
Arg
C
Leu
Pro
Gin
Arg
A
Leu
Pro
Gin
Arg
G
A
lie
Thr
Asn
Ser
U
lie
Thr
Asn
Ser
c
He
Thr
Lys
Arg
A
[Mëtl
Thr
Lys
Arg
G
G
Val
Ala
Asp
Gly
U
Val
Ala
Asp
Gly
C
Val
Ala
Glu
Gly
A
pVaf]
Ala
Glu
Gly
G
*The boxed codons are used for initiation. GUG is very rare.
of the codon at the left. The following features of the code
should be noted:
1. Sixty-one codons correspond to 20 different amino
acids.
2. The codon AUG has two functions. It corresponds to
the amino acid methionine when AUG occurs within
a coding sequence in the mRNA, i.e., within a
polypeptide chain. It also serves as a signal to initiate
polypeptide synthesis—with methionine for
eukaryotic cells but with N-formylmethionine for
prokaryotic cells. How the protein-synthesizing
system distinguishes an initiating AUG from an
internal AUG is discussed below. The codon GUG
also has both functions, but it is only rarely used in
initiation. Once initiation has occurred at an AUG
codon, the reading frame is established and the
subsequent codons are translated in order.
3. Three codons—UAA, UAG, and UGA—do not
represent any amino acid but serve as signals to
terminate the growing polypeptide chain.
4. Except for methionine (AUG) and tryptophan (UGG),
most amino acids are represented by more than one
codon. The assignment of codons is not random; with
the exception of serine, leucine, and arginine, all
synonyms (codons corresponding to the same amino
acid) are in the same box and differ by only the third
base. For example, GGU, GGC, GGA, and GGG all
code for glycine.
The fidelity of translation is determined by two features
of the system:
1. Attachment of the correct amino acid to a particular
tRNA molecule by the corresponding aminoacyl
synthetase, and
2. Correct codon-anticodon pairing. The former results
from the specificity of interaction of the enzyme, the
amino acid, and the tRNA molecule. The latter is
assured by base pairing.
A striking aspect of the code is that, with few excep-
tions, the third base in a codon appears to be unimportant,
i.e., XYA, XYB, XYC, and XYD are usually synonymous.
This finding has been explained by the base pairing prop-
erties of the anticodon-codon interaction. In DNA, no base
pairs other than GC and AT are possible because the reg-
ular helical structure of double-stranded DNA imposes
steric constraints. However, since the anticodon is located
within a single-stranded RNA loop, the codon-anticodon
interaction does not require formation of a structure with
the usual dimensions of a double helix. Model building in-
dicates that the steric requirements are less stringent at the
third position of the codon, a feature called
wobble.
The
wobble hypothesis allows for inosine (I), a nucleoside in
which the base is hypoxanthine and which is often found
in anticodons, to base-pair with A, U, or C. In addition,
the wobble hypothesis allows for U to base-pair with G.
This explains how a tRNA molecule carrying a particular
amino acid can respond to several different codons. For
example, two major species of yeast tRNAAla are known;
one responds to the codons GCU, GCC, and GCA and has
the anticodon IGC. Recall that the convention for nam-
ing the codon and the anticodon always has the 5' end at
the left. Thus, the codon 5'-GCU-3' is matched by the an-
ticodon S'-IGC^'. The other tRNAAla has the anticodon
CGC and responds only to GCG.
The function of three stop codons derives from the fact
that no tRNA exists that has an anticodon that can pair
with the stop codons.
Genetic Code of Mitochondria
The genetic code of mitochondria is not the same as the
“universal” code, which has implications for the evolu-
tion of mitochondria. Human mitochondria contain a set
of tRNA molecules that are not found elsewhere in the
