Transcript Creation/Evolution - Geoscience Research Institute

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
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 DNA nucleotide language is transcribed
into the RNA nucleotide language
The nucleotide language must be translated
into the amino acid language to make
proteins
©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
This means that there can only be 43 = 64
unique words
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
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
The Genetic Code
Helps To Control
The Impact Of
Point Mutations
©2000 Timothy G. Standish
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
Sentences
Genes can be thought of as sentences in the
nucleic acid language
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
Polypeptides are the sentences
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
Codon Assignment
Is Fortuitous
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
Codon Assignment
Is Fortuitous
Because of wobble base pairing, 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 truly
randomly assigned
Net probability is the likelihood of initial assignment
times probability of random assignment of remaining
43
codons
 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 to 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
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
Universal
Code
AAA=Asn
AUA=Ile
AAA=Asn
Vertebrates
Insects
Molluscs
Echinoderms
Nematodes
Platyhelmiths
Yeast/
Molds
Plants
Cytoplasm/
Nucleus
Variation in Mitochondrial
Codon Assignment
UGA/G=Stop
NOTE - This would mean
AUA changed from Ile to
Met, then changed back to
AUA=Met
Ile in the Echinoderms
AGA/G=Ser
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
©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:
1 Replacement of former stop codons in genes vital for life, and
whose activity will be destroyed, with still-functional stop codons
2 Production of new tRNAs with anticodons that recognize the
codon as an amino acid and not stop anymore
3 Modification of the release factor (eRF) to restrict its binding
specificity so that it no longer binds the former stop codon
All changes “appear to have occurred independently in
specific lines of evolution” (Lewin, Genes VI)
©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
Wobble Base
Pairing
©2000 Timothy G. Standish
The Rules of Codon
Anticodon Base Pairing
Three things affect the way in which base pairing
occurs between codons on mRNA and anticodons
on tRNA:
1 How the two molecules “twist” when annealing They are not free to form a perfect A helix
2 The environment of the Ribosome A site
3 Chemical modification of bases
These three factors change the usual base pairing
seen in DNA and RNA, particularly at the first base
of anticodons/third base of codons
©2000 Timothy G. Standish
Transfer RNA (tRNA)
Acceptor Arm - A
specific amino acid is
attached to the 3’ end
16 Pu
17
9
A
17:1
13 12 Py 10
1
2
3
4
5
6
U* 7
A
C
C
73
72
71
70
69
68
67
Py 59A*
66
65 64 63 62 C
D Arm - Contains
dihydrouridine
Py*
Pu
49 50 51 52 G T C
y
Py
G*
22 23 Pu 25
G
26
2020:120:2A
27
1
28
29
30
31
TyC arm - y stands
for pseudouridine
47:16
47:15
43 44
42 45
41 46
47
40
47:1
39
38
Pu*
U
34 35 36
Anticodon
Extra Arm - May
vary in size
©2000 Timothy G. Standish
Transfer RNA (tRNA)
H
H
H
H
O
Dihydrouridine
NH
N
O
16 Pu
17
9
A
17:1
13 12 Py 10
1
2
3
4
5
6
U* 7
A
C
C
73
72
71
70
69
68
67
Py 59A*
66
65 64 63 62 C
D Arm - Contains
dihydrouridine
Py*
Pu
49 50 51 52 G T C
y
Py
G*
22 23 Pu 25
G
26
2020:120:2A
27
1
28
29
30
31
TyC arm - y stands
for pseudouridine
47:16
47:15
43 44
42 45
41 46
47
40
47:1
39
38
Pu*
U
34 35 36
Anticodon
OPseudouridine
HN
NH
N
O
©2000 Timothy G. Standish
Base Pairing
Guanine And Cytosine
-
+
+
+
-
Base Pairing
Adenine And Uracil
+ -
Adenine
-
+
Uracil
Base Pairing
Adenine And Cytosine
+
-
-
Base Pairing
Guanine And Uracil
-
+
+
+
Uracil
Wobble Base Pairing
Guanine And Uracil
Uracil
- +
+
+
-
Base Pairing
Adenine And 2-Thiouracil
+ -
Adenine
-
+
2 Thiouracil
Wobble Base Pairing
Guanine And 2-Thiouracil
- +
2 Thiouracil
+
+
2-Thiouracil forms only one
hydrogen bond with guanine
which is not enough to form a
stable pair in the environment of
the ribosome A site
Wobble Base Pairing
Inosine And Cytosine
-
+
+
-
Wobble Base Pairing
Inosine And Uracil
Uracil
- +
+
-
Wobble Base Pairing
Inosine And Adenine
+
+
Adenine
-
The Wacky Rules of
Wobble Base Pairing
First anticodon
base:
Third codon
base:
U ------------- A or G
2-S-U ------ A
C ------------- G
A ------------- U
G ------------- C or U
I ------------- C U or G
©2000 Timothy G. Standish
Wobbling and tRNA Numbers
The net effect of wobble base pairing is to
reduce the number of tRNAs that must be
produced by a cell
In reality cells do not make 61 different
tRNAs, one for each codon
Many tRNAs have anticodons that anneal to
several different codons
Codons are known for which there are more
than one tRNA, although each tRNA carries
the same amino acid (i.e., methionine)
©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
©2000 Timothy G. Standish