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John 1:1-3

1 In the beginning was the Word,


and the Word was with God, and
the Word was God.
2 The same was in the beginning
with God.
3 All things were made by him;
and without him was not any
thing made that was made.
©1998 Timothy G. Standish
The
Language of
Life
Timothy G. Standish, Ph. D.

©1998 Timothy G. Standish


William
Start Dembski’s
Explanatory
Highly
probable? Yes
Filter
Law
No

Intermediate
probability? Yes Chance
No

Specified/
Small probability? Yes Design
No
From Mere Creation: Science, Faith and Intelligent
Design. William A. Dembski, ed. Downers Grove,
Chance IL: InterVarsity Press, 1998, p 99.
©1998 Timothy G. Standish
Outline:
 The genetic code: A brief introduction
 The genetic code helps control the impact of point
mutations
 The genetic code is improbable and does not look
random
 The genetic code is very unlikely to change
 The genetic code is not completely universal
 Summary

©1998 Timothy G. Standish


The Genetic
Code:
A Brief
Introduction

©1998 Timothy G. Standish


Introduction
The Central Dogma
of Molecular Biology

Cell

Transcription DNA

mRNA
Translation Ribosome

Polypeptide
(protein)
©1998 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.

©1998 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.

©1998 Timothy G. Standish


A Nucleotide
OH
Phosphate
NH2
HO P O Base
N N
O
N N
CH2
O
Sugar

OH H
OH
©1998 Timothy G. Standish
Two Families of Bases
Purines Pyrimidines
NH2 O O
Adenine Thymine Uracil
CH3 (DNA) (RNA)
N
N NH NH
N N N O N O
O
Guanine NH2
N Cytosine
NH
N
N N NH2
N O
©1998 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.

©1998 Timothy G. Standish


SUGAR-PHOS
OH
A Codon
NH2
HO P O
N
N Adenine

B A S E S
O
N N
CH2
O

O H
O

Guanine
HO P O
N
PHATE BACKB

O NH
N N NH2
CH2
O

O H
NH2
Arginine
Adenine
HO P O
N
O N
N N
CH2
O
ONE

OH H
©1998 Timothy G. Standish
The Genetic
Code
Helps To
Control The
Impact Of Point
Mutations©1998 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

©1998 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.
©1998 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

©1998 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

©1998 Timothy G. Standish


Comparison of
Languages
 English - God  DNA - CGT
 Chinese -  RNA - CGU
 Hieroglyphics -  Amino Acid -

Arginine

©1998 Timothy G. Standish


Redundancy:
Synonyms and Codon
Degeneracy
 English - Synonyms  Nucleic acids -
for God: Synonyms for
 Lord Arginine:
 CGU
 Father
 CGC
 Deity
 CGA
 the Almighty
 CGG
 Jehovah
 AGA
 AGG
©1998 Timothy G. Standish
The Genetic Code
Neutral Non-polar
Polar SECOND BASE
Basic
Acidic U C A G
F UUU
UUC
Phe
UCU
UCC
UAU
UAC
Tyr
UGU
UGC
Cys
U
C
T
I U UUA Leu UCA
Ser
UAA Stop UGA Stop A H
UUG UCG UAG UGG Trp G
R CUU CCU CAU CGU U
I
His
S C CUC
CUA
Leu CCC
CCA
Pro CAC
CAA
CGC
CGA
Arg C
A
R
Gln †
T CUG CCG CAG CGG G D
AUU ACU AAU AGU U
AUC Ile ACC AAC
Asn† AGC
Ser C
†Have amine B A AUA ACA
Thr
AAA Lys AGA Arg A B
AUGMet/start ACG AAG AGG G
groups
A GUU GCU GAU GGU U
A
Asp
*Listed as
S G GUC
GUA
Val GCC
GCA
Ala GAC
GAA
GGC
GGA
Gly* C
A
S
Glu
non-polar by E GUG GCG GAG GGG G E
some texts
©1998 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

©1998 Timothy G. Standish


Codon Assignment
Is Fortuitous
 Because 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

©1998 Timothy G. Standish


The Genetic
Code
Is Improbable
And Does Not
Look Random
©1998 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
0.0000000000000000000000000

 2.4  10 or 0000000000000000000000000
21 0000000000000000000000000
00000000024
©1998 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 codons
43
 1  1  1  60
   1.0  10
2164 21
©1998 Timothy G. Standish
Initial Codon
 Assignment
Theory would indicate initial codon assignment must have been
random
 Lewin in Genes VI, p 214, 215 suggests the following scenario:
1 A small number of codons randomly get meanings representing a few
amino acids or possibly one codon representing a “group” of amino
acids
2 More precise codon meaning evolves perhaps with only the first two
bases having meaning with discrimination at the third position
evolving later
3 The code becomes “frozen” when the system becomes so complex
that changes in codon meaning would disrupt existing vital proteins

©1998 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 6
Number of Codons

The genetic code does not like uneven numbers.


©1998 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

©1998 Timothy G. Standish


Codon Assignment
Is Not Strongly Correlated With
10
Use
Leu

8 Ala
Glu Gly Ser
%
Lys Val
In 6 Ile Thr
Asp
Proteins Gln Pro Arg
Asn
4 Phe
Tyr

2 Met His
Cys
Trp

1 2 3 4 5 6
Number of Codons
©1998 Timothy G. Standish
The Genetic
Code
Is Very Unlikely

To Change
©1998 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

©1998 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 3-
dimensional shape with A helices
 Associate a given amino acid with the
codon on the mRNA that codes for it

©1998 Timothy G. Standish


Translation - Initiation

fMet

Large P A
subunit E
UAC
5’GAG...CU-AUG--UUC--CUU--AGU--GGU--AGA--GCU--GUA--UGA-AT GCA...TAAAAAA 3’
Small mRNA
subunit

©1998 Timothy G. Standish


Translation - Elongation
Polypeptide
Met Arg
Phe
Leu Ser
Gly
Aminoacyl tRNA

Ribosome P A UCU
E
CCA
5’GAG...CU-AUG--UUC--CUU--AGU--GGU--AGA--GCU--GUA--UGA-AT GCA...TAAAAAA 3’
mRNA

©1998 Timothy G. Standish


Translation - Elongation
Polypeptide
Met
Phe
Leu Ser
Gly Arg

Aminoacyl tRNA

Ribosome P A
E
CCA UCU
5’GAG...CU-AUG--UUC--CUU--AGU--GGU--AGA--GCU--GUA--UGA-AT GCA...TAAAAAA 3’
mRNA

©1998 Timothy G. Standish


Protein Synthesis
AMINE H O ACID
Alanine Serine
H N C OH H O H O
C
H N C OH H N C OH
ANYTHING R H
H C H C
Amino Acid C H C H
H H HO H

H2O H O H O
H N C N C OH
H C H C
C H C H
H H HO H ©1998 Timothy G. Standish
Translation - Elongation
Polypeptide
Met
Phe
Leu Ser
Gly
Arg

Ribosome P A
E
CCA UCU
5’GAG...CU-AUG--UUC--CUU--AGU--GGU--AGA--GCU--GUA--UGA-AT GCA...TAAAAAA 3’
mRNA

©1998 Timothy G. Standish


Translation - Elongation
Polypeptide
Met
Phe Ala
Leu Ser
Gly
Arg Aminoacyl tRNA

Ribosome P A CGA
E
CCA
UCU
5’GAG...CU-AUG--UUC--CUU--AGU--GGU--AGA--GCU--GUA--UGA-AT GCA...TAAAAAA 3’
mRNA

©1998 Timothy G. Standish


Translation - Elongation
Polypeptide
Met
Phe
Leu Ser
Gly
Arg Ala

C CA
Ribosome P A
E
UCU CGA
5’GAG...CU-AUG--UUC--CUU--AGU--GGU--AGA--GCU--GUA--UGA-AT GCA...TAAAAAA 3’
mRNA

©1998 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

©1998 Timothy G. Standish


Making
Aminoac
Amino-
Gly acyl-tRNA
Synthetase
A

P
P
ATP Amino-
yl-tRNA
P Gly acyl-tRNA
Synthetase
P A
P
P Pyrophosphate
Amino-
Gly acyl-tRNA
Synthetase

Amino- P A
Gly
acyl-tRNA AMP
Synthetase

CCA

Aminoacyl- Note that the amino acid is not paired with the
tRNA tRNA on the basis of the anticodon. The correct
tRNA for a given amino acid is recognized on
CCA the basis of other parts of the molecule.
©1998 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

©1998 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)

©1998 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

©1998 Timothy G. Standish


The Genetic
Code
Is Not
Completely
Universal
©1998 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.

©1998 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 Common Meaning Modified Meaning
Tetrahymena thermophila UAA UAG Stop glutamine
A ciliate
Paramecium UAA UAG Stop glutamine
A ciliate
Euplotes octacarinatus UGA Stop cysteine
A ciliate
Mycoplasma capricolum UGA Stop tryptophan
A bacteria
Candida CUG serine leucine
A yeast
Neutral Non-polar, Polar ©1998 Timothy G. Standish
Variation in
Mitochondrial Codon
Assignment

Platyhelmiths

Echinoderms

Vertebrates
Cytoplasm/

Nematodes

Molluscs
Nucleus

Insects
Molds
Yeast/
Plants

AUA=Met AAA=Asn AUA=Ile UGA/G=Stop


CUN=Thr AAA=Asn
 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
Universal
Code  Differences in mtDNA lower the number of tRNAs needed
©1998 Timothy G. Standish
Summary:
Are Codons The Language of
 The genetic code appears to God?
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

©1998 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.

©1998 Timothy G. Standish


Question 1
 How many bases are in a codon?
A 1
B 2
C 3
D 4
E 5

©1998 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

©1998 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

©1998 Timothy G. Standish


Translation
Polypeptide
Met Arg
Phe
Leu Ser
Gly Aminoacyl tRNA

Ribosome P A UCU

CCA
5’GAGCU-AUG--UUC--CUU--AGU--GGU--AGA--GCU--GUA--UGA-ATAAAAAA 3’
mRNA

©1998 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 3- dimensional
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

©1998 Timothy G. Standish


Met-tRNA
Methionine
A
C
C
73
1 72
2 71
3 70
4 69
5 68
6 67
U* 7 66 Py 59 A*
65 64 63 62 C
1716 A
Pu
9 Pu
17:1
13 12 10
Py 49 50 51 52 G T C
G* Py

G 22 23 Pu 25 47:16

2020:120:2A 26 47:15
27
1 4344
28 42 45
29 41 46
30 40 47
47:1
31 39
Py* 38
U Pu*
34
U 35
A 36
C
Anticodon ©1998 Timothy G. Standish
Problem 1
 Transcribe and translate the following DNA
sequence:
3’
AATAGTACCGCAAATTTATCGCTT5’
5’
UUAUCAUGGCGUUUAAAUAGCGAA3’
5’
UUAUC,AUG,GCG,UUU,AAA,UAG,CGAA3’
Met--Ala--Phe--Lys--Stop

©1998 Timothy G. Standish


The Genetic Code
Neutral Non-polar
Polar SECOND BASE
Basic
Acidic U C A G
F UUU
UUC
Phe
UCU
UCC
UAU
UAC
Tyr
UGU
UGC
Cys
U
C
T
I U UUA Leu UCA
Ser
UAA Stop UGA Stop A H
UUG UCG UAG UGG Trp G
R CUU CCU CAU CGU U
I
His
S C CUC
CUA
Leu CCC
CCA
Pro CAC
CAA
CGC
CGA
Arg C
A
R
Gln †
T CUG CCG CAG CGG G D
AUU ACU AAU AGU U
AUC Ile ACC AAC
Asn† AGC
Ser C
†Have amine B A AUA ACA
Thr
AAA Lys AGA Arg A B
AUGMet/start ACG AAG AGG G
groups
A GUU GCU GAU GGU U
A
Asp
*Listed as
S G GUC
GUA
Val GCC
GCA
Ala GAC
GAA
GGC
GGA
Gly* C
A
S
Glu
non-polar by E GUG GCG GAG GGG G E
some texts
©1998 Timothy G. Standish

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