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Institute
of
Molecular Biotechnology
Swetlana Nikolajewa and Thomas Wilhelm
Institute of Molecular Biotechnology Jena, Germany,
http://www.imb-jena.de/tsb
Jena
We present a new classification scheme of the genetic code, based on a binary representation of purines (A, G = 1) and pyrimidines (U, C = 0). On the basis of this
logical organization we detect codon regularities (strong, mixed and weak codons) and patterns of amino acid properties and show symmetry characteristics of the genetic
code. We present the “codon - reverse codon” pattern and use it to remove the only ambiguity which had remained in our recently proposed new classification scheme of
the genetic code. The purine-pyrimidine scheme has now found its final form.
We show that the “codon - reverse codon” pattern is correlated to aspects of the tRNA anticodon distribution in all organisms. It is well known that there is no tRNA with
an anticodon for any of the STOP codons; we found that there is also no tRNA containing reverse STOP anticodons.
The four combinations of the first column (CC*, GC*, CG*, and GG*) always
imply 6 hydrogen bonds in complementary base-paring with the corresponding
anticodon of the tRNA. Accordingly, they are called strong codons.
The classification scheme of the genetic
code is based on a binary representation of
purines (G,A)
- 1,
pyrimidines (C,U) - 0.
The first two bases guarantee 5 H-bonds: mixed codons.
The eight rows (23 = 8) and four columns are
sufficient to place the 20 amino acids, as
well as the termination codons.
Code
The common table of the standard genetic code
Second Letter
First
Letter
U
C
UUU
A
UCU
Phe
G
UAU
Ser
Third
Letter
UGU
Tyr
UCC
UAC
UGC
UUA
UCA
UAA
UGA
Stop
A
UGG
Trp
G
UUG
UCG
CUU
CCU
Leu
C
C
CGU
His
CCC
CAC
CGC
C
CUA
CCA
CAA
CGA
A
Leu
Pro
CCG
AUU
ACU
Ile
AUC
AUA
ACA
AUG
Met
GUU
ACG
GUC
GCC
4 hydrogen bonds
Pro CC
Ser UC
(C/U)
Leu
(C/U)
CU
(C/U)
Phe UU
(C/U)
Pro CC (A/G)
Ser
UC
(A/G)
Leu CU
(A/G)
Leu UU
100
Ala GC
(C/U)
Thr AC
(C/U)
Val GU
(C/U)
Ile AU
101
Ala GC
(A/G)
Thr
AC
(A/G)
Val GU
(A/G)
Ile / Met AU
010
Arg CG
(C/U)
Cys
UG
(C/U)
His
CA
(C/U)
Tyr UA
011
Arg
CG
(A/G)
Gln CA
(A/G)
Stop UA (A/G)
110
Gly
GG
(C/U)
Asp GA
(C/U)
Asn AA
(A/G)
(C/U)
(A/G)
(C/U)
A
G
GGU
Asp
GAC
5 hydrogen bonds
Arg
AGG
GAU
Ala
C
AGA
Lys
AAG
GCU
Val
U
Ser
AGC
AAA
Thr
5 hydrogen bonds
U
Gly
GGC
C
Stop / Trp UG (A/G)
G
GUA
GCA
Val
GUG
GAA
Ala
GCG
GGA
Glu
GAG
Interestingly, in 5 different mitochondrial
codes (including yeast) AU(A/G) always
encodes for Met and UG(A/G) encodes Trp.
Thus, 32 positions code for 32 entries and
each row contains exactly four different
amino acids. In this spirit the
mitochondrial code is the most regular
one.
G
AGU
Asn
AAC
6 hydrogen bonds
Each row contains exactly 4 different
amino acids (including the stop codon).
Exceptions in the standard code are the
second row with two leucines and the
fourth row with the AU* start codon.
Arg
CGG
AAU
Thr
ACC
Ile
Gln
CAG
Weak codons
U
Arg
CUC
CUG
A
CAU
Pro
Mixed codons
001
Stop
UAG
Mixed codons
U
UUC
Ser
Strong codons
Cys
U
Leu
000
Weak codons have
just 4 H-bonds .
A
The codon-anticodon symmetry: the red
horizontal line marks the symmetry axis.
For instance, codon CCC (Pro, first
column, first row) has the anticodon GGG
(Gly, first column, last row).
Gly
GGG
G
111
Gly
GG
Ser AG
(A/G)
Arg
(C/U)
AG
In 8 different mitochondrial codes UG(A/G)
encodes Trp.
(A/G)
Glu GA
(A/G)
Lys AA
(C/U)
(A/G)
The arrows represent “codon - reverse codons” pairs.
The point symmetry corresponds to
Halitsky’s family – nonfamily symmetry
operation (“E-M bifurcation”, Halitsky
2003). For instance, the family codon GUA
(Val) is mapped into the nonfamily codon
UGC (Cys). Thus, this point symmetry is
behind the family – nonfamily symmetry in
our scheme (shaded vs. unshaded
regions).
“Codon - Reverse Codon” Pattern
The arrows in the above table indicate “codon - reverse codons” pairs: the reverse codon of a codon XYZ is defined as ZYX, where X, Y, Z can be any base. For
instance, the reverse codon of GGA (Gly) is AGG (Arg). There exist 15 different amino acids in the rows 000, 101, 010 and 111 where the codon is reverse to
itself, e.g. Lys (AAA), Tyr (UAU).
Stop
1. The table can be divided into four blocks (codon - reverse codon groups) of the same size, for instance the upper
left block with Pro (P), Ser (S), Ala (A) and Thr (T). Each block shows the same arrow pattern. All strongly
evolutionary conserved groups of amino acids (Thompson et al., 1994) are subsets of exactly one codon - reverse
codon group, e.g. the MILV amino acids belong to the upper right block in the table. The other conserved strong
groups belonging to one block are STA, NEQK, NHQK, NDEQ, QHRK, MILF, HY. The only exception is FYW.
2. We studied all known tRNA genes of 104 different organisms (Sprinzl et al., 1999). It is known that the STOP
codons do not have any tRNA. We found that there are also no tRNA genes containing anticodons reverse to the
STOP anticodons (ACT, ATC and ATT in Table 2). The only exception is H. sapiens, possessing one tRNAAsn gene
with the anticodon ATT, but humans also have three different possible suppressor tRNA genes (Lowe and Eddy,
1997).
AUC
UAG
STOP
Asp
CUA
GAU
Asp
Table 2. The amino acid codon- reverse codon pairs and
the number of tRNA genes for the corresponding anticodons.
Codons
AA
Reverse Codons
Anticodons
# tRNAs
AA
Anticodons
# tRNAs
Stop
UGA
TCA
0
Ser
AGU
ACT
0
Stop
UAG
CTA
0
Asp
GAU
ATC
0
Stop
UAA
TTA
0
Asn
AAU
ATT
1
Tyr
UAC
GTA
189
His
CAU
ATG
0
Trp
UGG
CCA
144
Gly
GGU
ACC
0
Leu
UUA
TAA
127
Ile
AUU
AAT
1
Leu
UUG
CAA
134
Val
GUU
AAC
18
Phe
UUC
GAA
154
Leu
CUU
AAG
28
Ser
UCA
TGA
151
Thr
ACU
AGT
19
Ser
UCC
GGA
116
Pro
CCU
AGG
16
3. There are some anticodons, where the reverse anticodon has no tRNA, e.g. all 104
studied organisms have at least one tRNA for Tyr with anticodon GTA (some organisms, for
instance H.sapiens, have different tRNAs with the same anticodon, altogether there are 189
different tRNAs with the anticodon GTA in the 104 species), but no organism has a tRNA for
His with anticodon ATG. Table 2 lists different codon - reverse codon pairs. In the whole
superkingdom bacteria the number of tRNA genes for the reverse part of table 2 is always
zero, the few exceptions are only in eukaryotes and archaea. Another unique property of all
bacteria is that there is no tRNA with anticodons for the self reverse codons UUU (Phe),
UCU (Ser), UGU (Cys) and UAU (Tyr). Generally, table 2 shows that anticodons with an A at
the third position are strongly preferred, whereas A** anticodons are significantly
suppressed.
REFERENCES
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