Transcript Creation/Evolution

John 1:1-3
1
2
3
In the beginning was the Word, and
the Word was with God, and the
Word was God.
The same was in the beginning
with God.
All things were made by him; and
without him was not any thing
made that was made.
©2000 Timothy G. Standish
The Language
of Life
Timothy G. Standish, Ph. D.
©2000 Timothy G. Standish
Start
Highly
probable?
William Dembski’s
Explanatory Filter
Yes
Law
Yes
Chance
Yes
Design
No
Intermediate
probability?
No
Specified/
Small probability?
No
Chance
From Mere Creation: Science, Faith and Intelligent
Design. William A. Dembski, ed. Downers Grove,
IL: InterVarsity Press, 1998, p 99.
©2000 Timothy G. Standish
Introduction
The Central Dogma
of Molecular Biology
Cell
DNA
Transcription
Translation
mRNA
Ribosome
Polypeptide
(protein)
©1998 Timothy G. Standish
Information Only Goes One Way
The central dogma states that once “information”
has passed into protein it cannot get out again.
The transfer of information from nucleic acid
to nucleic acid, or from nucleic acid to protein,
may be possible, but transfer from protein to
protein, or from protein to nucleic acid, is
impossible. Information means here the precise
determination of sequence, either of bases in
the nucleic acid or of amino acid residues in
the protein.
Francis Crick, 1958
©2000 Timothy G. Standish
The Genetic Language
 The
genetic code is a written language
not unlike English or German.
 While English uses 26 letters to spell
out words, genetic languages use only 4
nucleotide “letters”.
 The nucleotide language of DNA is
transcribed into the nucleotide language
of RNA.
©2000 Timothy G. Standish
The Nucleotide Language
 DNA
- ATGCATGCATGC
 RNA - AUGCAUGCAUGC
 It
is not unlike different Bible versions.
 Psalm 139:14
 KJV I will praise thee; for I am fearfully
and wonderfully made: marvelous are thy
works; and that my soul knoweth right well.
 NIV I praise you because I am fearfully and
wonderfully made; your works are
wonderful, I know that full well.
©2000 Timothy G. Standish
Nucleotide Words
 Words
in the nucleotide
language are all 3 letters or
bases long.
 These three base “words” are
called codons
 This means that there can only
be 43 = 64 unique words.
©2000 Timothy G. Standish
A Codon
OH
P
HO
NH2
O
N
O
CH2
N
O
P
O
O
N
O
CH2
P
NH
N
O
Guanine
NH2
N
H
O
HO
N
H
O
HO
Adenine
N
NH2
O
N
O
CH2
O
OH
N
N
Adenine
Arginine
N
H
©1998 Timothy G. Stan
Redundancy in the Code
 Codons
code for only 20 words, or amino
acids.
 In addition to the amino acids, the start and
stop of a protein need to be coded for
 There are thus a total of 22 unique
meanings for the 64 codons, so many
codons are synonyms.
 The fact that many amino acids are coded
for by several codons is called degeneracy
©2000 Timothy G. Standish
Why Not Use Shorter
Codons?
 If
each codon was only 2 bases
long, there would be 42 = 16
possible unique codons
 This would not provide enough
unique meanings to code for the 22
things (20 amino acids plus start
and stop) that have to be coded for.
©2000 Timothy G. Standish
Sentences
 Sentences
in the nucleic-acid language are
called genes.
 Each gene contains a sequence of codons
that describe the primary structure (amino
acid sequence) of a polypeptide (protein).
 At the beginning of each gene is a start
codon
 In the middle is a sequence of codons for
amino acids
 At the end is a stop codon
©2000 Timothy G. Standish
The Protein Language
 The
protein language is very different from
the nucleotide language
 Sentences are called polypeptides or
proteins
 It is analogous to pictographic languages
like Chinese or Egyptian Hieroglyphics.
 Each symbol has a meaning in pictographic
languages and in proteins, each amino acid
has a unique meaning or specific effect.
 Words are not a sequence of nucleotides,
but each AA in the primary structure
©2000 Timothy G. Standish
Comparison of Languages
 English
- God
 Chinese  Hieroglyphics -
 DNA
- CGT
 RNA - CGU
 Amino
Acid Arginine
©2000 Timothy G. Standish
Redundancy:
Synonyms and Codon Degeneracy






English - Synonyms
for God:
Lord
Father
Deity
the Almighty
Jehovah







Nucleic acids Synonyms for
Arginine:
CGU
CGC
CGA
CGG
AGA
AGG
©2000 Timothy G. Standish
The Genetic Code
Neutral Non-polar
Polar
Basic
Acidic
F
I U
R
S C
T
†Have amine
groups
*Listed as
non-polar by
some texts
B A
A
S G
E
SECOND
U
UUU
UUC
UUA
UUG
CUU
CUC
CUA
CUG
Phe
Leu
Leu
C
UCU
UCC
UCA
UCG
CCU
CCC
CCA
CCG
AUU
AUC Ile
AUA
AUGMet/start
ACU
ACC
ACA
ACG
GUU
GUC
GUA
GUG
GCU
GCC
GCA
GCG
Val
BASE
A
Ser
UAU
UAC
UAA
UAG
Tyr
Pro
CAU
CAC
CAA
CAG
His
Thr
AAU
AAC
AAA
AAG
Asn†
Ala
GAU
GAC
GAA
GAG
Asp
Stop
Gln†
Lys
Glu
G
UGU
UGC
UGA
UGG
CGU
CGC
CGA
CGG
AGU
AGC
AGA
AGG
GGU
GGC
GGA
GGG
Cys
Stop
Trp
U
C
A
G
Arg
U
C
A
G
Ser
Arg
Gly*
U
C
A
G
U
C
A
G
T
H
I
R
D
B
A
S
E
©2000 Timothy G. Standish
Different Amino Acid Classes
O Cysteine
O
Alanine
H2N
C
H
H
C
H
C OH
H2N
Generic
H
Non-polar
O
Amine
H2N
O
Aspartic
acid
H2N
C
H
C
Acid OH
H
H
C
HS
Polar
Acid
H
C OH
O Histidine
H
H2 N
C
H
H
C
O
C OH
?R
C
C
H
C OH
H
C
Basic
C
C
H+N
C OH
H
NH
C
©2000 Timothy G. Standish
Non-Polar
Amino Acids
Glycine O
C OH
H2N
C
Valine O
H
H
C OH
H2N
C
H
H
C
H
C
H
C
H2N
C
H
C OH
H
C
H
CH3
Isoleucine O
H2 N
C
H3C
H
C
H3C
H
C
H
H
C OH
C
H
C OH
H
C
H
C OH
H
H
C
H3C
H
PhenylalanineO
C
C
H
CH3
H3 C
H2N
H
H
H2N
Leucine O
C OH
H2 N
Alanine O
MethionineO
H
C
H
S
H3C
Tryptophan O
H2 N
C
H
C OH
H
C
H
Proline O
+
NH H2N
C OH
H2C
C
H2C CH2 H
©2000 Timothy G. Standish
Polar Amino Acids
Serine O
H2N
C
H
C OH
H2N
H
H2N
C
H
H2N
H
C
H
H
C
HS
Asparagine O
C OH
H
C
H
NH2
Glutamine O
HO
H2N
C OH
C
H
H
C
O
C
C OH
H
C
H
H
C
O
H
C
H
H
Cysteine O
C
H
OH
C
C OH
H2N
C OH
H
C
CH3
HO
C
H
H
C
Tyrosine O
Threonine O
H
NH2
©2000 Timothy G. Standish
Acidic Amino Acids
Aspartic O
acid
C OH
H2 N
C
H
H
C
O
C
H
H
OH
Glutamic O
acid
C OH
H2N
C
H
H
C
H
C
O
C
H
OH
©2000 Timothy G. Standish
Basic Amino Acids
Histidine O
H2N
C
H
C
C
C
H+N
C OH
Lysine O
H2N
H
C
H
H
NH
C
+H
3N
H
H
C
H
N
+H
2N
H
C
H
C OH
H
C
H
H
C
C
H
H
C
H
H2N
H
C
H
Arginine O
H
C
H
C OH
H
C
NH2
©2000 Timothy G. Standish
Levels Of Protein Organization
Primary Structure - The sequence of amino acids
in the protein
 Secondary Structure - The formation of a helices
and b pleated sheets due to hydrogen bonding
between the peptide backbone
 Tertiary Structure - Folding of helices and sheets
influenced by R groups
 Quaternary Structure - The association of more
than one polypeptide into a protein complex
influenced by R groups

©2000 Timothy G. Standish
Levels Of Protein Organization
Primary Structure
DNA
5’...ATG GCA GCA AAG AAT AGA ACC ATT AAG GTT...3’
3’...TAC CGT CGT TTC TTA TCA TGG TAA TTC CAA...5’
Transcription
RNA
5’...AUG GCA GCA AAG AAU AGA ACC AUU AAG GUU...3’
Translation
Protein
Met-Ala-Ala-Lys-Asn-Arg-Thr-Ile-Arg-Val...
A one-to-one correspondence exists between the DNA
sequence of a gene and the primary structure of proteins
©2000 Timothy G. Standish
Glyceraldehyde-3-Phosphate
Dehydrogenase Primary Structure

The Mycoplasma genitalium G-3P dehydrogenase
protein sequence:

MAAKNRTIKV AINGFGRIGR LVFRSLLSKA NVEVVAINDL
TQPEVLAHLL KYDSAHGELK RKITVKQNIL QIDRKKVYVF
SEKDPQNLPW DEHDIDVVIE STGRFVSEEG ASLHLKAGAK
RVIISAPAKE KTIRTVVYNV NHKTISSDDK IISAASCTTN
CLAPLVHVLE KNFGIVYGTM LTVHAYTADQ RLQDAPHNDL
RRARAAAVNI VPTTTGAAKA IGLVVPEANG KLNGMSLRVP
VLTGSIVELS VVLEKSPSVE QVNQAMKRFA SASFKYCEDP
IVSSDVVSSE YGSIFDSKLT NIVEVDGMKL YKVYAWYDNE
SSYVHQLVRV VSYCAKL
Protein Secondary Structure
 The
peptide backbone of protein has
areas of positive charge and negative
charge
 These areas can interact with one
another to form hydrogen bonds
 The result of these hydrogen bonds are
two types of structures:
a helices
b pleated sheets
©2000 Timothy G. Standish
H
N
Protein Secondary Structure:
H
C
a
Helix
C
N
O
C
C
O
H
C
N
H
N
C
O
H
C
N
C
O
C
O
C
O
C
C
O
H
C
N
H
H
H
N
H
O
N
C
N
O
C
OH
C
H
C
H
+
-
C
H
H C
H
H HO
H
©2000 Timothy G. Standish
H
N
Protein Secondary Structure:
H
C
a
Helix
C
N
O
C
C
O
H
C
N
H
N
C
O
H
C
N
C
O
C
O
C
O
C
C
O
H
C
N
H
H
H
N
H
O
N
C
N
O
C
OH
C
H
C
H
+
-
C
H
H C
H
H HO
H
©2000 Timothy G. Standish
Protein Secondary Structure:
a Helix
R groups stick out
from the a helix
influencing higher
levels of protein
organization
R
R
R
R
R
R
R
R
R
R
R
R
R
R
©2000 Timothy G. Standish
M
S
L
R
Q
S
I
Yeast Cytochrome C
Oxidase Subunit IV Leader
L
First 12 residues are sufficient for
transport to the mitochondria
R
F
F
K
T
A
P
P


T
C
R
MLSLRQSIRFFKPATRTLCSSRYLL
R
L
S
S
Neutral Non-polar
Polar
Basic
Acidic

This leader sequence probably forms an a helix
This would localize specific classes of amino
acids in specific parts of the helix
There are about 3.6 amino acids per turn of the
helix with a rise of 0.54 nm per turn
Y
L
©2000 Timothy G. Standish
Protein Secondary Structure:
b Pleated Sheet
C
O
C
H
C N
C
O
N
H
O
C
N
H
C
C
C
O
H
N
C
O
C
H
C N
C
O
N
H
O
C
N
H
C
C
C
O
H
N
C
O
C
H
C N
C
O
N
H
O
C
N
H
C
C
C
O
H
N
C
O
C
H
C N
C
O
N
H
O
C
N
H
C
C
O
H
N
C
©2000 Timothy G. Standish
Protein Secondary Structure:
b Pleated Sheet
C
O
C
N
H
O
C
N
H
C
C
O
N
H
O
C
C
H
C N
C
C
O
C
C
O
C
H
C N
N
H
O
C
N
H
C
C
O
N
H
O
C
H
N
H
C N
O
C
C
C
O
C
C
O
C
H
C N
N
H
O
C
N
H
C
C
O
N
H
O
C
H
N
H
C N
O
C
C
C
O
C
C
O
C
H
C N
C
O
N
H
O
C
H
N
H
C N
O
C
N
H
O
C
N
H
C
C
O
H
N
C
H
C N
C
O
©2000 Timothy G. Standish
Levels Of Protein Organization
Tertiary Structure
Tertiary structure results from the folding of a
helices and b pleated sheets
 Factors influencing tertiary structure include:
 Hydrophobic/hydrophilic interactions
 Hydrogen bonding
 Disulfide linkages
 Folding by chaperone proteins

©2000 Timothy G. Standish
G-3-P Dehydrogenase
Tertiary Structure
Picture source: SWISS-PROT
©2000 Timothy G. Standish
Levels Of Protein Organization
Quaternary Structure
 Quaternary structure results from the interaction
of independent polypeptide chains
 Factors influencing quaternary structure include:
 Hydrophobic/hydrophilic interactions
 Hydrogen bonding
 The shape and charge distribution on associating
polypeptides
©2000 Timothy G. Standish
G-3-P Dehydrogenase
from Bacillus stearothermophilus
Skarzynski, T., Moody, P. C. E., Wonacott, A. J. 1987. Structure of HoloGlyceraldehyde-3-Phosphate Dehydrogenase from Bacillus Stearothermophilus
Picture source: SWISS-PROT
at 1.8 Angstroms Resolution. J.Mol.Biol. 193:171
©2000 Timothy G. Standish
The Globin Gene Family
Globin genes code for the
a
b
protein portion of hemoglobin
 In adults, hemoglobin is made
Fe
up of an iron containing heme
molecule surrounded by 4
globin proteins: 2 a globins
b
a
and 2 b globins
 During development, different globin genes are
expressed which alter the oxygen affinity of
embryonic and fetal hemoglobin

©2000 Timothy G. Standish
Haemoglobin
Luisi, B., Shibayama, N. 1989. Structure of Haemoglobin in the Deoxy Quaternary State
with Ligand Bound at the Alpha Haems. J.Mol.Biol. 206:723
Picture source: SWISS-PROT
©2000 Timothy G. Standish
Ribosomes
The Protein Factories
 Ribosomes
are the organelles in which
the mRNA nucleotide language is
translated into the protein language
 The two ribosome subunits are made
up of ribosomal RNA (rRNA) and
proteins
 Ribosomes in eukaryotes follow the
same basic plan as those in prokaryotes
although they are slightly larger
©2000 Timothy G. Standish
Ribosome Structure
Peptidyl-tRNA
binding site
Aminoacyl-tRNA
binding site
P
Exit site
A
E
5’
Large
subunit
GAG...C-AGGAGG-NNNNNNNNNN-AUG---NNN---NNN---NNN---NNN--mRNA
3’
Small subunit
©2000 Timothy G. Standish
Ribosome Structure
Yellow:
30S
subunit,
blue: 50S
subunit
E. coli ribosome at 25 A resolution from Frank et al. 1995. Biochem. Cell Biol. 73:757-767.
(see also Frank et al. 1995. Nature 376:441-444.)
©2000 Timothy G. Standish
E. Coli Ribosome In 4 D
©2000 Timothy G. Standish
How Codons Work:
tRNA the Translators
 tRNA
- Transfer RNA
 Relatively small RNA molecules that
fold in a complex way to produce a 3dimensional shape with a specific
amino acid on one end and an
anticodon on another part
 Associate a given amino acid with the
codon on the mRNA that codes for it
©2000 Timothy G. Standish
Met-tRNA
Methionine
D Loop
16 Pu
17
9
A
17:1
13 12 Py 10
1
2
3
4
5
6
U* 7
A
C
C
73
72
Acceptor stem
71
70
69
TyGC Loop
68
67
Py 59A*
66
65 64 63 62 C
49 50 51 52 G T C
y
Py
G*
22 23 Pu 25
G
26
2020:120:2A
27
1
28
29
30
Anticodon loop
31
Py*
Anticodon
Pu
47:16
47:15
43 44
42 45
41 46
47
40
47:1
39
38
Variable loop
Pu*
U
34
U 35
C
A 36
©2000 Timothy G. Standish
Initiation
 The
small ribosome subunit binds to the 5’
untranslated region of mRNA
 The small ribosomal subunit slides along the
mRNA 5’ to 3’ until it finds a start codon
(AUG)
 The initiator tRNA with methionine binds to
the start codon
 The large ribosomal subunit binds with the
initiator tRNA in the P site
©2000 Timothy G. Standish
Translation - Initiation
fMet
Large
subunit
E
P
A
UAC
5’GAG...CU-AUG--UUC--CUU--AGU--GGU--AGA--GCU--GUA--UGA-AT GCA...TAAAAAA
3’
Small mRNA
subunit
©2000 Timothy G. Standish
Translation - Elongation
Polypeptide
Arg
Met
Phe
Leu
Ser
Aminoacyl tRNA
Gly
Ribosome
E
P
A
CCA
5’GAG...CU-AUG--UUC--CUU--AGU--GGU--AGA--GCU--GUA--UGA-AT GCA...TAAAAAA
3’
mRNA
©2000 Timothy G. Standish
Translation - Elongation
Polypeptide
Met
Phe
Leu
Ser
Gly
Arg
Aminoacyl tRNA
Ribosome
E
P
A
CCA UCU
5’GAG...CU-AUG--UUC--CUU--AGU--GGU--AGA--GCU--GUA--UGA-AT GCA...TAAAAAA
3’
mRNA
©2000 Timothy G. Standish
Protein Synthesis
AMINE H
H
O
N
ACID
C
C
ANYTHING
R
H
Amino Acid
Alanine
OH
H
H
Serine
H
O
N
C
OH
H
C
H
H
H
H2O
H
H
C
H
C
H
O
C
N
OH
C
HO
N
H
O
C
C
C
H
H C
H
H HO
H
OH
C
H
H
N
H
H
C
O
©2000 Timothy G. Standish
Translation - Elongation
Polypeptide
Met
Phe
Leu
Ser
Gly
Arg
Ribosome
E
P
A
CCA UCU
5’GAG...CU-AUG--UUC--CUU--AGU--GGU--AGA--GCU--GUA--UGA-AT GCA...TAAAAAA
3’
mRNA
©2000 Timothy G. Standish
Translation - Elongation
Polypeptide
Met
Phe
Leu
Ala
Ser
Gly
Aminoacyl tRNA
Arg
Ribosome
E
P
A
CCA
UCU
5’GAG...CU-AUG--UUC--CUU--AGU--GGU--AGA--GCU--GUA--UGA-AT GCA...TAAAAAA
3’
mRNA
©2000 Timothy G. Standish
Translation - Elongation
Polypeptide
Met
Phe
Leu
Ser
Gly
Arg
Ribosome
E
Ala
P
A
UCU CGA
5’GAG...CU-AUG--UUC--CUU--AGU--GGU--AGA--GCU--GUA--UGA-AT GCA...TAAAAAA
3’
mRNA
©2000 Timothy G. Standish
Aminoacyl-tRNA Synthetase
 Aminoacyl-tRNA
Synthetase enzymes
attach the correct amino acids to the
correct tRNA
 This is an energy-consuming process
 Aminoacyl-tRNA Synthetases
recognize tRNAs on the basis of their
looped structure, not by direct
recognition of the anticodon
©2000 Timothy G. Standish
Gly
P
P
Aminoacyl-tRNA
Synthetase
P
ATP
Gly
P
P
P
Aminoacyl-tRNA
Synthetase
Making
AminoacyltRNA
Pyrophosphate
Gly
P
Aminoacyl-tRNA
Synthetase
©2000 Timothy G. Standish
Gly
P
P
Making
AminoacyltRNA
Aminoacyl-tRNA
Synthetase
P
ATP
Gly
P
P
P
Aminoacyl-tRNA
Synthetase
Pyrophosphate
Gly
Aminoacyl-tRNA
Synthetase
Gly
Aminoacyl-tRNA
Synthetase
P
AMP
CCA
AminoacyltRNA
CCA
Note that the amino acid is not paired with the
tRNA on the basis of the anticodon. The correct
tRNA for a given amino acid is recognized on
the basis of other parts of
the molecule.
©2000 Timothy G. Standish
Requirements for Translation







Ribosomes - rRNA and Proteins
mRNA - Nucleotides
tRNA
– The RNA world theory might explain these three
components
Aminoacyl-tRNA Synthetase,
– A protein, thus a product of translation and cannot be
explained away by the RNA world theory
L Amino Acids
ATP - For energy
This appears to be an irreducibly complex system
©2000 Timothy G. Standish
The Genetic Code
Is Very Unlikely
To Change
©2000 Timothy G. Standish
Changing Initial Codon
Assignment

Once codons have been assigned to an amino
acid, changing their meaning would require:
– Changing the tRNA anticodon or, much harder,
changing the aminoacyl-tRNA synthetase
– Changing all codons to be reassigned in at least the
vital positions in those proteins needed for survival
This seems unlikely
 The situation is complicated in cases where
genes seem to have been swapped between the
nucleus and mitochondria

©2000 Timothy G. Standish
Reassignment of Stop Codons


Changes in stop codon meaning must have occurred after
meanings were “frozen” in other organisms; alternatively
organisms that exhibit them must have evolved from
organisms that never shared the universal genetic code
All changes in stop codons must include three changes:
– Replacement of stop codons that do not code for stop anymore
with those that still do
– Production of new tRNAs with anticodons that recognize the
codon as not stop anymore
– Modification of the release factor (eRF) to restrict its binding
specificity further so that it no longer binds the stop codon with
new meaning

All changes “appear to have occurred independently in
specific lines of evolution” (Lewin, Genes VI)
©2000 Timothy G. Standish
The Genetic Code
Buffers Against the
Impact of Point
Mutations
©2000 Timothy G. Standish
The Sickle Cell Anemia Mutation
Normal b-globin DNA
C
Mutant b-globin DNA
T
T
C
G A
A
G U A
mRNA
mRNA
Normal b-globin
Mutant b-globin
Glu
H2 N
C
C
A T
Val
O
OH
H
CH2
H2C
C OH
O Acid
H2 N
C
C
O
OH
H
CH
CH3
H3C
Neutral
Non-polar
©1998 Timothy G. Standish
Sickle Cell Anemia:
A Pleiotropic Trait
Mutation of base 2 in b globin codon 6 from A to T
causing a change in meaning from Glutamate to Valine
Mutant b globin is produced
Breakdown of
red blood cells
Anemia
Clogging of small
blood vessels
Tower skull
Weakness
Heart failure
Impaired
mental function
Accumulation of sickled
cells in the spleen
Red blood cells sickle
Brain
damage
Paralysis
Pain and
Fever
Damage to
other organs
Rheumatism
Kidney
failure
Spleen
damage
Infections
especially
pneumonia
©2000 Timothy G. Standish
Codon Assignment Helps Prevent
Deleterious Point Mutations
Effect of mutations is minimized in the genetic
code:
 Mutation of the third base in a codon changes the
codon meaning only 1/3 of the time
 In AAs with only two codons, the mutation always
has to be purine to pyrimidine or vice versa to
change the AA coded for.
 This is much harder than purine to purine or
pyrimidine to pyrimidine mutation

©2000 Timothy G. Standish
 Because
Codon Assignment
Is Fortuitous
of wobble base pairing, this
arrangement means less than 61 tRNAs have
to be made
 53% of purine to purine or pyrimidine to
pyrimidine mutations in the second position
result in codons with either the same
meaning (i.e., UAA to UGA both = stop) or
coding for chemically related amino acids
©2000 Timothy G. Standish
The Genetic Code
Is Improbable And
Does Not Look
Random
©2000 Timothy G. Standish
Possible Codon Assignments

The probability of getting the assignment of codons to
amino acids we have can be calculated as follows:
– There are 21 meanings for codons:



20 amino acids
1 stop
1 start, which doesn’t count because it also is assigned to methionine
– 64 Codons

If we say that each codon has an equal probability of being
assigned to an amino acid, then the probability of getting
any particular set of 64 assignments is:
64
 1 
85
or

2.4

10
21
0.0000000000000000000000000
0000000000000000000000000
0000000000000000000000000
00000000024
©2000 Timothy G. Standish
Problems With Codon
Assignment




Under Miller-Urey type conditions, more than the 20 amino
acids would have been available
To estimate probability, we assume only 20, but this
changes the odds
As all 20 amino acids and “stop” must be assigned one
codon, only 64 - 21 = 43 codons could be truely randomly
assigned
Net probability is the likelyhood of initial assignment times
probability of random assignment of remaining codons
43
 1  1  1 
60
 1.0  10


216421
©2000 Timothy G. Standish
Initial Codon Assignment


1
2
3
Theory would indicate initial codon assignment must
have been random
Lewin in Genes VI, p 214, 215 suggests the following
scenario:
A small number of codons randomly get meanings
representing a few amino acids or possibly one codon
representing a “group” of amino acids
More precise codon meaning evolves perhaps with only
the first two bases having meaning with discrimination at
the third position evolving later
The code becomes “frozen” when the system becomes so
complex that changes in codon meaning would disrupt
existing vital proteins
©2000 Timothy G. Standish
Codon Assignment
Does not look random
9
8
7
6
Amino 5
Acids 4
3
2
1
0
1
2
3
4
5
Number of Codons
6
The genetic code does not like uneven numbers.
©2000 Timothy G. Standish
Initial Codon Assignment
 If
natural selection worked on codons,
the most commonly used amino acids
might be expected to have the most
codons
 If there was some sort of random
assignment, the same thing might be
expected
 This is not the case
©2000 Timothy G. Standish
Codon Assignment
Is Not Strongly Correlated With Use
10
Leu
8
Glu
%
In 6
Proteins
Lys
Asp
Gln
Asn
Phe
4
Ile
Ala
Gly
Ser
Val
Thr
Pro
Arg
Tyr
2
Met
His
Cys
Trp
1
2
3
4
Number of Codons
5
6
©2000 Timothy G. Standish
The Genetic Code
Is Not Completely
Universal
©2000 Timothy G. Standish
Further Attention
“While the evidence for an
adaptive code is clear, the
process by which the code
achieved this optimization
requires further attention.”
Freeland et al.
©2000 Timothy G. Standish



Variation In Codon Meaning
Lack of variation in codon meanings across almost all phyla is
taken as an indicator that initial assignment must have occurred
early during evolution and all organisms must have descended
from just one individual with the current codon assignments
Exceptions to the universal code are known in a few single-celled
eukaryotes and mitochondria and at least one prokaryote
Most exceptions are modifications of the stop codons UAA, UAG
and UGA
Organism
Codon/s
Tetrahymena thermophila UAA UAG
A ciliate
Paramecium
UAA UAG
A ciliate
Common Meaning Modified Meaning
Stop
glutamine
Stop
glutamine
Euplotes octacarinatus
UGA
Stop
cysteine
Mycoplasma capricolum
UGA
Stop
tryptophan
Candida
CUG
serine
leucine
A ciliate
A bacteria
A yeast
Neutral Non-polar, Polar
©2000 Timothy G. Standish
AUA=Met
CUN=Thr
AAA=Asn
AUA=Ile
AAA=Asn
AUA=Met
Vertebrates
Insects
UGA/G=Stop

NOTE - This would mean AUA
changed from Ile to Met, then
changed back to Ile in the
Echinoderms
AAA must have changed from Lys to
Asn twice
UGA=Trp
 UGA must have changed to Trp then back to stop
 Differences in mtDNA lower the number of tRNAs needed
AGA/G=Ser
Universal
Code
Molluscs
Echinoderms
Nematodes
Platyhelmiths
Yeast/
Molds
Plants
Cytoplasm/
Nucleus
Variation in Mitochondrial
Codon Assignment

©2000 Timothy G. Standish
Summary:
Are Codons The Language of God?





The genetic code appears to be non-random in nature and
designed with considerable safeguards against harmful
point mutations
An evolutionary model suggests at least at some level of
randomness in assignment of amino acids to codons
No mechanism exists for genetic code evolution
Thus variation in the genetic code suggests a polyphyletic
origin for life
Taken together, this evidence indicates the hand of a
Designer in the genetic code and does not support the
theory that life originated due to random processes or that
all organisms share a common ancestor
©2000 Timothy G. Standish
Psalms 33:8, 9
8
Let all the earth fear the Lord:
Let all the inhabitants of the
world stand in awe of him.
9
For he spake, and it was done;
he commanded and it stood
fast.
©2000 Timothy G. Standish
Eukaryotic Gene Expression
Cytoplasm
Packaging
Degradation
DNA
Transcription
Transportation
Modification
RNA
RNA
Processing
mRNA G
G
AAAAAA
Nucleus
Export
Degradation etc.
AAAAAA
Translation
©2000 Timothy G. Standish
Protein Production and
Transport
Ribosomes
Cytoplasm
Rough
Nucleus
Endoplasmic
Reticulum
Smooth
Gogi
Complex
©2000 Timothy G. Standish
Protein Production
Mitochondria and Chloroplasts
Cytoplasm
Nucleus
G
AAAAAA
Export
Mitochondrion
Chloroplast
©2000 Timothy G. Standish
Protein Production
Mitochondria and Chloroplasts
Cytoplasm
Nucleus
Mitochondrion
Chloroplast
©2000 Timothy G. Standish
Question 1
 How
A
B
C
D
E
many bases are in a codon?
1
2
3
4
5
©2000 Timothy G. Standish
Question 2
True or False
 A) Mutating just one base in a codon may have a
profound effect on the protein being coded for and
consequently the organism
 B) Mutating the third base in a codon frequently
has no effect on the protein being coded for
 C) Changing an amino acid in a protein will have
less effect on a protein if the amino acid belongs
to the same class as the original amino acid it is
replacing
©2000 Timothy G. Standish
Question 3
Which of the following components of the
translation process cannot be explained away
by the RNA World theory?
 A) mRNA
 B) Ribosomes
 C) Aminoacyl-tRNA transferase
 D) tRNA

©2000 Timothy G. Standish
Problem 1
 Transcribe
and translate the following DNA
sequence:
DNA3’ATAGTACCGCAAATTTATCGCTT5’
RNA 5’UAUCAUGGCGUUUAAAUAGCGAA3’
mRNA
Cap-5’UAUC,AUG,GCG,UUU,AAA,UAG,CGAA3’Poly A tail
Protein
Met--Ala--Phe--Lys--Stop
©2000 Timothy G. Standish
The Genetic Code
Neutral Non-polar
Polar
Basic
Acidic
F
I U
R
S C
T
†Have amine
groups
*Listed as
non-polar by
some texts
B A
A
S G
E
SECOND
U
UUU
UUC
UUA
UUG
CUU
CUC
CUA
CUG
Phe
Leu
Leu
C
UCU
UCC
UCA
UCG
CCU
CCC
CCA
CCG
AUU
AUC Ile
AUA
AUGMet/start
ACU
ACC
ACA
ACG
GUU
GUC
GUA
GUG
GCU
GCC
GCA
GCG
Val
BASE
A
Ser
UAU
UAC
UAA
UAG
Tyr
Pro
CAU
CAC
CAA
CAG
His
Thr
AAU
AAC
AAA
AAG
Asn†
Ala
GAU
GAC
GAA
GAG
Asp
Stop
Gln†
Lys
Glu
G
UGU
UGC
UGA
UGG
CGU
CGC
CGA
CGG
AGU
AGC
AGA
AGG
GGU
GGC
GGA
GGG
Cys
Stop
Trp
U
C
A
G
Arg
U
C
A
G
Ser
Arg
Gly*
U
C
A
G
U
C
A
G
T
H
I
R
D
B
A
S
E
©2000 Timothy G. Standish