1. 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.

2. The Genetic Code: The Language of Life
Timothy G. Standish, Ph. D.

3. 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

4. The Universal Language
"[The universe] is written in the language of mathematics, and its characters are triangles, circles, and other geometrical figures, without which it is humanly impossible to understand a single word of it ”
Galileo Galilei, The Controversy on the Comets of 1618

5. 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

6. The Nucleotide Language
DNA - ATGCATGCATGC
RNA - AUGCAUGCAUGC
It is not unlike different Bible versions.
Psalms 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.

7. 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.

8. A Codon Guanine Arginine Adenine B A S E S SUGAR-PHOSPHATE BACKBONE O
CH2
NH2 N NH OH
Guanine
Adenine
Arginine
©1998 Timothy G. Standish

9. The Genetic Code Helps To Control The Impact Of Point Mutations

10. 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
Because all codons are used many act as synonyms, having different sequences, but the same meaning
The fact that many amino acids are coded for by several codons is called degeneracy

11. 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, acting like a capital letter is the start codon
In the middle is a sequence of codons for amino acids
The period at the end is a stop codon

12. 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

13. Comparison of Languages
English - God
Chinese -
Hieroglyphics -
DNA - CGT
RNA - CGU
Amino Acid -
Arginine

14. 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

15. The Genetic Code U C A G U C A G S E C O N D B A S E F I R S T B A E T
Stop Codon Names
- Ochre
- Amber
-Not named
UAA
UAG
UGA
Neutral Non-polar
Polar
Basic
Acidic
S E C O N D B A S E U C A G F I R S T B A E U
UUU
UUC
UUA
UUG
UCU
UCC
UCA
UCG
UAU
UAC
UAA
UAG
UGU
UGC
UGA
UGG U C A G T H I R D B A S E
Phe
Tyr
Cys
Ser
Stop
Leu
Stop
Trp C
CUU
CUC
CUA
CUG
CCU
CCC
CCA
CCG
CAU
CAC
CAA
CAG
CGU
CGC
CGA
CGG U C A G
His
Leu
Pro
Arg
Gln† A
AUU
AUC
AUA
AUG
ACU
ACC
ACA
ACG
AAU
AAC
AAA
AAG
AGU
AGC
AGA
AGG U C A G
Asn†
Ser
Ile
Thr
Lys
Arg
†Have amine
groups
Met/
start G
GUU
GUC
GUA
GUG
GCU
GCC
GCA
GCG
GAU
GAC
GAA
GAG
GGU
GGC
GGA
GGG U C A G
Asp
Val
Ala
Gly*
*Listed as
non-polar by
some texts
Glu

16. 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

17. 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

18. The Genetic Code Is Improbable And Does Not Look Random

19. 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: or

20. 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 amion acids and “stop” must be assigned one codon, only = 43 codons could be truely randomly assigned
Net probability is the likelyhood of initial assignment times probability of random assignment of remaining codons

21. Initial Codon Assignment
Theory would indicate initial codon assignment must have been random
Lewin in Genes VI pp 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

22. Codon Assignment Does not look random
The genetic code does not like uneven numbers.

23. 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

24. Codon Assignment Is Not Strongly Correlated to Use
Met
Trp
Cys
His
Tyr
Phe
Thr
Arg
Ser
Leu
Pro
Ile
Gln
Asp
Lys
Glu
Asn
Val
Gly
Ala
Number of Codons 10 8 6 4 2 % In
Proteins

25. The Genetic Code Is Not Completely Universal

26. 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
serine
Stop
Common Meaning
Candida
A yeast
Euplotes octacarinatus
A ciliate
Paramecium
Organism
Tetrahymena thermophila
leucine
cysteine
glutamine
Modified Meaning
CUG
UGA
UAA UAG
Codon/s
Mycoplasma capricolum
A bacteria
tryptophan
Neutral Non-polar, Polar

27. Variation in Mitochondrial Codon Assignment
UGA/G=Stop
Universal
Code
Cytoplasm/
Nucleus
Plants
Yeast/
Molds
Platyhelmiths
Echinoderms
Molluscs
Insects
Vertebrates
UGA=Trp
AGA/G=Ser
AUA=Met
CUN=Thr
AUA=Ile
AAA=Asn
Nematodes
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 must have changed to Trp then back to stop
Differences in mtDNA lower the number of tRNAs needed

28. 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 former stop codons in genes vital for life, and whose activity will be destroyed, with still functional stop codons
Production of new tRNAs with anticodons that recognize the codon as an amino acid and not stop anymore
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)

29. 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

30. Wobble Base Pairing

31. 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:
How the two molecules “twist” when annealing - They are not free to form a perfect A helix
The environment of the Ribosome A site
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

32. Transfer RNA (tRNA) Anticodon
Acceptor Arm - A specific amino acid is attached to the 3’ end U* 9 26 22 23 Pu 16 12 Py 10 25
20:1 G*
17:1 A
20:2 17 13 20 G 50 51 65 64 63 62 52 C 59 y A* T 49 39 41 42 31 29 28
Pu* 43 1 27 U 35 38 36
Py* 34 40 30
47:1
47:15 46
47:16 45 44 47 73 70 71 72 66 67 68 69 3 2 7 6 5 4
TyC arm - y stands for pseudouridine
D Arm - Contains dihydrouridine
Extra Arm - May vary in size
Anticodon

33. Transfer RNA (tRNA) Dihydro-uridine O NH N Pseudo-uridine O HN NH C9 26 22 23 Pu 16 12 Py 10 25
20:1 G*
17:1 A
20:2 17 13 20 G 50 51 65 64 63 62 52 C 59 y A* T 49 39 41 42 31 29 28
Pu* 43 1 27 U 35 38 36
Py* 34 40 30
47:1
47:15 46
47:16 45 44 47 73 70 71 72 66 67 68 69 3 2 7 6 5 4
TyC arm - y stands for pseudouridine
D Arm - Contains dihydrouridine
Pseudo-uridine O HN NH C
Anticodon

34. Base Pairing Guanine And CytosineH O N
Guanine - N O H
Cytosine + + - - +

35. Base Pairing Adenine And UracilH - +
Adenine N O H + -
Uracil

36. Base Pairing Adenine And CytosineH
Cytosine - + N H - +
Adenine

37. Base Pairing Guanine And UracilH O N
Guanine + - N O H + -
Uracil

38. Wobble Base Pairing Guanine And UracilH
Uracil + - H O N
Guanine + -

39. Base Pairing Adenine And 2-Thiouracil+
Adenine N S O H + -
2 Thio-
uracil

40. Wobble Base Pairing Guanine And 2-Thiouracil+ - S N O H
2 Thio-
uracil +
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

41. Wobble Base Pairing Inosine And CytosineH
Inosine + - N O H
Cytosine - +

42. Wobble Base Pairing Inosine And UracilH
Uracil + - O N H
Inosine - +

43. Wobble Base Pairing Inosine And AdenineH
Inosine + - N H - +
Adenine

44. The Wacky Rules of Wobble Base Pairing
First anticodon base:
Third codon base: U
2-S-U C A G I
A or G A G U
C or U
C U or G

45. Modified RNA Bases: UridineH O C N
Uridine H O C N
Dihydrouridine (D) H O C N
Pseudouridine () H S C N
4-thiouridine (S4U) O H O C N
Ribothymidine (T)

46. 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 (ie methionine)

47. 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

48. The
End

49. Modified RNA Bases: UridineH O C N
Dihydrouridine H O C N
Uridine H O C N
Ribothymidine H O C N
Pseudouridine

50. Other Modified RNA Bases: Cytidine

51. Other Modified RNA Bases: AdenosineC N
Adenosine