SECTION 25.6
Genetic Code
573
TABLE 25-3
Genetic Code o f Human Mitochondria
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
Trp
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
Ille |
Thr
Asn
Ser
U
lie
Thr
Asn
Ser
C
Met)“ Thr
Lys
Stop*
A
Met
Thr
Lys
Stop*
G
G
Val
Ala
Asp
Gly
U
Val
Ala
Asp
Gly
C
Val
Ala
Glu
Gly
A
Val
Ala
Glu
Gly
G
*These entries are found in mitochondria but not in the univeral code.
Boxed codons are used as start codons. The mitochondrial codes of
other organisms exhibit further differences.
cell and a circular DNA molecule containing 16,569 base
pairs. This DNA molecule encodes some mitochondrial
enzymes (Chapter 14) and is the template for synthesis
of all mitochondrial tRNA and rRNA molecules. Human
mitochondrial DNA sequences contain the genes for 12S
and 16S ribosomal RNA, 22 different tRNA molecules,
three subunits of the enzyme cytochrome oxidase (whose
amino acid sequence is known), cytochrome b, and several
other enzymes. The human mitochondrial code is shown
in Table 25-3; entries shown with an asterisk differ from
the universal code (cf. Table 25-2). The differences are
striking in that most are in the initiation and termination
codons. That is, in mammalian mitochondria,
1. UGA codes for tryptophan and not for termination.
2. AGA and AGG are termination codons rather than
codons for arginine.
3. AUA and AUU are initiation codons, as is AUG. Both
AUA and AUG also code for methionine. AUU also
codes for isoleucine, as in the universal code.
4. AUA codes for methionine (and initiation, as shown
in item 3) instead of isoleucine.
Maize mitochondria use CGG for tryptophan rather than
for arginine, and CGU, CGC, and CGA for arginine. Yeast
mitochondria use CUX, where X is any base, for threonine
rather than for leucine. Both maize and yeast use AGA and
AGG for arginine. Evidently, various mitochondrial codes
can differ from each other as well as from the universal
code.
The
number
of mammalian
mitochondrial
tRNA
molecules is 22, which is less than the minimum number
(32) needed to translate the universal code. This is possible
because in each of the fourfold redundant sets—e.g., the
four alanine codons GCU, GCC, GCA, and GCG—only
one tRNA molecule (rather than two, as explained above)
is used. In each set of four tRNA molecules, the base in
the wobble position of the anticodon is U or a modified U
(not I). It is not yet known whether this U is base-paired in
the codon-anticodon interaction or manages to pair weakly
with each of the four possible bases. For those codon sets
that are doubly redundant—e.g., the two histidine codons
CAU and CAC—the wobble base always forms, a G-U
pair, as in the universal code. The structure of the human
mitrochondrial tRNA molecule is also different from that
of the standard tRNA molecule (except for mitochondrial
tRNALeuUUX). (X = any nucleotide.) The most notable
differences are the following:
1. The universal sequence CU//CXA is lacking in
mitochondrial tRNA.
2. The “constant” 7-bp sequence of the Ti/fC loop varies
from three to nine bases.
3. The invariant bases U8, A14, G15, G18, G19, and
U48 of the standard tRNA molecule are not invariant
in mitochondrial tRNA.
In standard tRNA molecules, each of these bases parti-
cipates in bonds that produce the
folded L-shaped
molecule. Thus, the mitochondrial tRNA molecule seems
to
be
stabilized
by
fewer
interactions.
The
three-
dimensional configurations of these molecules are not
known with certainty; possibly they differ from the stan-
dard L-shape, and mitochondrial tRNA engages in a dif-
ferent type of interaction with the ribosome than standard
tRNA molecules do.
Most DNA molecules contain long noncoding segments
(spacers)
between genes. In mitochondrial DNA, there
are either a few bases or none. In each case, there is a
start codon (AUG, AUA, or AUU) at the 5' end of the
mRNA molecule or within a few bases of it. This arrange-
ment differs from the usual arrangement for eukaryotes
in that ordinarily eukaryotic mRNA molecules commence
with a short leader sequence thought to be responsible for
binding to the ribosome. Such a leader is not present in
the mitochondrial mRNA molecules, which suggests that
