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THE GENETIC CODE
● Prepared by → Mughal Gumar
Farooq
● M.Sc. Semester 1
● Department of zoology, JU
ABSTRACT
> CENTRAL DOGMA
> INTRODUCTION
> DECIPHERING OF GENETIC CODE
> CODON
> ANTICODON
> PROPERTIES OF GENETIC CODE
> WOBBLE HYPOTHESIS
> MUTATION
CENTRAL DOGMA
● The “central Dogma” is a process by which the information stored in DNA is
transferred to mRNA molecules during transcription and to proteins during
translation.
● First proposed by Francis crick in 1958
● It explain the flow of genetic information from
DNA → RNA → Protein
● the process by which DNA instructions are converted into the functional
product is called gene expression.
● Gene expression has two key stages transcription and translation.
● Transcription is the first step in gene expression – transfers the genetic
information stored in DNA(genes) into messenger RNA molecules that carry
the information to the ribosomes.
CENTRAL DOGMA
• the pathway of protein synthesis is
called translation because the
language of nucleotide sequence on
mRNA is translated into the language of
amino acid sequence
• the process of Translation requires a
GENETIC CODE through which the
information contained in nucleic acid
sequence is expressive to produce a
specific sequence of amino acid
● The genetic code is non-overlapping sequence ,with each
amino acid, plus polypeptide initiation and termination
specified by RNA codon composed of three nucleotide.
● Genetic code is composed of nucleotide triplets.
● The term was given by George Garrow
● George Garrow postulate that three nucleotide or three letter code
must be applied to encode the 20 standard amino acid used by living
cell to build protein
● The genetic code was discovered by Marshall Nirenberg and his
colleagues in 1961.
● Nirenberg and his colleague Johann H Matthaei showed that a triplet
of uracils (U) coded for the amino acid phenylalanine (F).
● Nirenberg, Robert W. Holley, and Har Gobind Khorana won the Nobel
prize in 1968 for deciphering the genetic code.
GENETIC CODE
INTRODUCTION TO GENETIC CODE
● RNA is composed of four nucleotide, adenine (A) , guanine (G) , cytosine (
C) and uricils (U)
● Three adjacent nucleotide constitute a unit known as Codon, which code for
an amino acid
● The collection of codon is called Genetic code.
● There are 64 possible codon , 3 of which do not code for amino acid but
indicate the termination of polypeptide chains.
● The remaining 61 codon specify 20 amino acid that make up protein.
● Each codon should have 3 nucleotide to impart specificity to each of the
amino acid for specific Codon
1 nucleotide → (4 x1) 4 combination. (Singlet)
2 nucleotide → (4x4) 16 combination. (Douplet)
3 nucleotide → (4x4x4) 64 combination.(Triplet)
DECIPHERING THE GENETIC CODE
• The decade of 1960s-the era of cracking of the genetic code - was on the
most exciting time in the history of biology.
•The Triplet Hypothesis.
• George Gamow→Genetic code is Triplet.
•Experiments with Synthetic mRNA.
• Nirenberg and Heinrich Matthaei. → cell free content
•The Poly-U Experiment
• (UUUUUUUUU) →phenylalanine
•The Poly-UC Experiment
• Gobind Khorana (UCUCUCUCU) →serine and leucine.
• By 1966 M. Nirenberg, R. Holly, H. Gobind khorana, Severo Ochoa , Philip
leader and their colleague worked out the meaning of all 64 triplet codons
for all 20 amino acids.
GENETIC CODE CHART
CODON
● Genetic code is a Dictionary consist of “ Genetic word “ called codon.
● A codon is a three-nucleotide or triplet sequence found on mRNA that
codes for a certain amino acid during translation
● Cell decode mRNA by reading their nucleotide in a group of 3 , called
codon
FEATURES
→ Most codon specify an amino acid.
→ Written in 5 to 3` direction
→ Three “stop” codon UAA , UAG , UGA marks the end of protein
→ One “start” codon AUG marks the beginning of protein and also encode
the amino acid methionine
TYPES OF CODON
1) Sense codon → Codon that code for amino acid
2) Signal codon → codon that code for signal during protein synthesis,
TYPES OF SIGNAL CODON
1) INITIATION CODON
• AUG is used to initiate polypeptide chains, in rare instances, GUG is used
as an initiation codon.
• In prokaryotes, an AUG codon must follow an appropriate nucleotide
sequence, the Shine-delgarno sequence (AGGAGGU), in the 5’ nontranslated
segment of the mRNA molecule in order to serve as translation initiation
codon
•AUG code for methionine
in eukaryotes and archaea
and N-formyl methionine
in bacteria, mitochondria
and plastid.
•GUG codes for the amino
acid valine
TERMINATION CODON
• Three codon—-UAA, UAG, UGA are termination codon that specify
polypeptide chain termination .
• Often referred to as Ochra, Amber and Opal codon.
• These codon are recognised by Protein release factor, rather than tRNAs.
•Prokaryots contain two release
factors Rf-1 and Rf-2.
•Rf-1 terminates polypeptide in
response to codon UAA and
UAG whereas RF-2 causes
termination at UAA and UGA
codons.
• Eukaryotes contain a single
release factor that recognizes
all three termination codons.
ANTICODON
● The ANTICODON is a specific sequence of
three nucleotides in a transfer RNA (tRNA)
molecule that is complementary to a
corresponding codon in messenger RNA
(mRNA).
● The codon-anticodon interaction is a key
step in the process of translation during
protein synthesis.
FEATURES
• Written in 3-5` direction.
• it help in bringing a particular amino acid at
its proper position during translation
• always present in RNA and never in DNA.
1) Triplet nature
2) Degenarcy
3) Non-overlapping
4) Universal
5) Commaless
6) Non-ambiguous
7) Polarity
CHARACTERISTICS OF GENETIC CODE
1) THE CODE IS TRIPLET
→ Singlet and doublet codes and not adequate to code for 20
amino acid; therefore, it was pointed out that Triplet code is
the maximum required
→ The Triplet code has 64 codon which is sufficient to code for
20 amino acid and also for start and stop Signal in the
synthesis of polypeptide chain
→ In a Triplet code three RNA bases code for one amino acid
2) THE CODE IS DEGENERATE/ REDUNDANT
→the occurrence of more than one
codon per amino acid is called
degeneracy.
• One amino acid (isoleucine) by 3 codon.
• Five amino acid by 4 codon each.
• Two amino acid by 6 codon each.
•Nine amino acid are coded by 2 codon
each
→ This multiple system of coding is known
as Degenerate or redundant code
system.
Exception →Only two amino acid viz,
Tryptophan and methionine are coded by
one amino acid each.
DEGENERATE AND ORDERED CODE
The degeneracy in the genetic code is not at random instead it is highly
ordered.Degeneracy is primarily of two types
> Partial Degeneracy
Ocuur when the first two nucleotides are identical but the third nucleotide
of the degenerated codon differ. eg UUU and UUC code for Phenylalanine.
> Complete Degeneracy.
Occur when any of the 4 bases can take third position in codon and still
code for the same amino acid. Eg. UCU, UCC, UCA, UCG all code for serine.
Scientists have speculated that the order in the genetic code has evolved
as a way of minimizing mutational lethality.
Many base substitutions at the third position of codons do not change the
amino acid specified by the codon. Moreover, amino acids with similar
chemical properties (such as leucine, isoleucine, and valine) have codons
that differ from each other by only one base.
3) THE CODE IS NON-OVERLAPPING
→A non-overlapping code means that the same latter is not used for two
different codon
→ In other words , no single base can take part in the formation of more than
one codon
→ The adjacent code doesn't overlap.
e.g There are bases , CATGAT
→ Non-overlapping code : 2 i.e CAT and GAT
→ Overlapping code :4 i.e CAT, GAT , ATG, TAT
4) THE CODE IS UNIVERSAL
→ The genetic code is nearly Universal.
→University of Codon means that the
same sequence of 3 bases encode the
same amino acids in all life forms from
simple microorganism to complex,
multicelled organism such as human
being.
→ the codon have same meaning in all
living organisms
→ However, some exception have been
found.
● 5) THE CODE IS COMMALESS
→ There is no signal to indicate the end of one codon and the
beginning of the next.
→ In other words , the Codon is continuous and there are no
demarcation lines between Codon
6) THE CODE IS NON-AMBIGUOUS
→ Non-ambiguous code means that there is no ambiguity about a particular
codon
→ A particular codon will always code for the same amino acid.
→ While the same codon will no code for two or more different amino acid.
→ In case of ambiguous code , one codon should code fro more than one
amino acid. In the genetic code there is no ambiguity.
7) THE CODE HAS POLARITY
→ The code is always read in the fixed direction i.e in the
5 →3’ direction
→ If the code is read in opposite direction (i.e 3→5) ,it would
specify 2 different proteins, since the code will have reserved base
sequence.
WOBBLE HYPOTHESIS
→WOBBLE means to SWAY or MOVE UNSTEADILY.
→ HISTORY: hypothesis proposed by Francis Crick in 1966 to explain the
observed Degeneracy in the third position of a codon.
→According to The Wobble Hypothesis, only the first two bases of the codon
have a precise pairing with the bases of the anticodon of tRNA, while the pairing
between the third bases of codon and anticodon may Wobble.
Statement
Wobble hypothesis states that the genetic codes are degenerate. It explains that
the third base pairing varies with respect to the base at the third position like U
may pair with A or G.
→The phenomenon permits a single tRNA to recognize more than one codon
Therefore, although there are 61 codons for amino acids, the number of tRNA is
far less (around 40) which is due to wobbling.
SIGNIFICANCE OF WOOBLE HYPOTHESIS
→Wobble base pairs are fundamental in RNA secondary structure and
are critical for the proper translation of the genetic code.
→Wobbling allows faster dissociation of tRNA from mRNA and also
protein synthesis
→The existence of wobble minimizes the damage that can be caused
by a misreading of the code; for example, if the Leu codon CUU were
misread CUC or CUA or CUG during transcription of mRNA, the codon
would still be translated as Leu during protein synthesis.
BIOLOGICAL SIGNIFICANCE OF DEGENERACY OF
GENETIC CODE
● If the code were not degenerate, 20 code would specify 20 amino acid and
44 would lead to chain termination
● he probability of mutating chain termination would therefore be much
higher with a non degenerate codon
MUTATIONS AND GENETIC CODE
● Mutations results in change of nucleotide sequence in DNA and RNA
● Effect of mutation is on translation through alteration in Codon
● Some mutations are harmful.
● Some of them are
● > Point mutations → Silent, misense and nonsense
● > Frame Shift mutations.
MUTATIONS AND GENETIC CODE
● POINT MUTATION →The replacement of one base pair by another
results in point mutations
● SILENT MUTATION →There are no detectable effects in silent
mutation.
MIS SENSE MUTATION → The changed base may code for a different amino acid
MUTATIONS AND GENETIC CODE
NONSENSE MUTATION→ The codon with altered base may become termination (
or nonsense) codon
MUTATIONS AND GENETIC CODE
● FRAME SHIFT MUTATION → these occur with one or more
base pair is inserted in or deleted from DNA
Genetic Code. A comprehensive overview..pdf

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Genetic Code. A comprehensive overview..pdf

  • 1. THE GENETIC CODE ● Prepared by → Mughal Gumar Farooq ● M.Sc. Semester 1 ● Department of zoology, JU
  • 2. ABSTRACT > CENTRAL DOGMA > INTRODUCTION > DECIPHERING OF GENETIC CODE > CODON > ANTICODON > PROPERTIES OF GENETIC CODE > WOBBLE HYPOTHESIS > MUTATION
  • 3. CENTRAL DOGMA ● The “central Dogma” is a process by which the information stored in DNA is transferred to mRNA molecules during transcription and to proteins during translation. ● First proposed by Francis crick in 1958 ● It explain the flow of genetic information from DNA → RNA → Protein ● the process by which DNA instructions are converted into the functional product is called gene expression. ● Gene expression has two key stages transcription and translation. ● Transcription is the first step in gene expression – transfers the genetic information stored in DNA(genes) into messenger RNA molecules that carry the information to the ribosomes.
  • 4. CENTRAL DOGMA • the pathway of protein synthesis is called translation because the language of nucleotide sequence on mRNA is translated into the language of amino acid sequence • the process of Translation requires a GENETIC CODE through which the information contained in nucleic acid sequence is expressive to produce a specific sequence of amino acid
  • 5. ● The genetic code is non-overlapping sequence ,with each amino acid, plus polypeptide initiation and termination specified by RNA codon composed of three nucleotide. ● Genetic code is composed of nucleotide triplets. ● The term was given by George Garrow ● George Garrow postulate that three nucleotide or three letter code must be applied to encode the 20 standard amino acid used by living cell to build protein ● The genetic code was discovered by Marshall Nirenberg and his colleagues in 1961. ● Nirenberg and his colleague Johann H Matthaei showed that a triplet of uracils (U) coded for the amino acid phenylalanine (F). ● Nirenberg, Robert W. Holley, and Har Gobind Khorana won the Nobel prize in 1968 for deciphering the genetic code. GENETIC CODE
  • 6. INTRODUCTION TO GENETIC CODE ● RNA is composed of four nucleotide, adenine (A) , guanine (G) , cytosine ( C) and uricils (U) ● Three adjacent nucleotide constitute a unit known as Codon, which code for an amino acid ● The collection of codon is called Genetic code. ● There are 64 possible codon , 3 of which do not code for amino acid but indicate the termination of polypeptide chains. ● The remaining 61 codon specify 20 amino acid that make up protein. ● Each codon should have 3 nucleotide to impart specificity to each of the amino acid for specific Codon 1 nucleotide → (4 x1) 4 combination. (Singlet) 2 nucleotide → (4x4) 16 combination. (Douplet) 3 nucleotide → (4x4x4) 64 combination.(Triplet)
  • 7.
  • 8.
  • 9. DECIPHERING THE GENETIC CODE • The decade of 1960s-the era of cracking of the genetic code - was on the most exciting time in the history of biology. •The Triplet Hypothesis. • George Gamow→Genetic code is Triplet. •Experiments with Synthetic mRNA. • Nirenberg and Heinrich Matthaei. → cell free content •The Poly-U Experiment • (UUUUUUUUU) →phenylalanine •The Poly-UC Experiment • Gobind Khorana (UCUCUCUCU) →serine and leucine. • By 1966 M. Nirenberg, R. Holly, H. Gobind khorana, Severo Ochoa , Philip leader and their colleague worked out the meaning of all 64 triplet codons for all 20 amino acids.
  • 11. CODON ● Genetic code is a Dictionary consist of “ Genetic word “ called codon. ● A codon is a three-nucleotide or triplet sequence found on mRNA that codes for a certain amino acid during translation ● Cell decode mRNA by reading their nucleotide in a group of 3 , called codon FEATURES → Most codon specify an amino acid. → Written in 5 to 3` direction → Three “stop” codon UAA , UAG , UGA marks the end of protein → One “start” codon AUG marks the beginning of protein and also encode the amino acid methionine TYPES OF CODON 1) Sense codon → Codon that code for amino acid 2) Signal codon → codon that code for signal during protein synthesis,
  • 12. TYPES OF SIGNAL CODON 1) INITIATION CODON • AUG is used to initiate polypeptide chains, in rare instances, GUG is used as an initiation codon. • In prokaryotes, an AUG codon must follow an appropriate nucleotide sequence, the Shine-delgarno sequence (AGGAGGU), in the 5’ nontranslated segment of the mRNA molecule in order to serve as translation initiation codon •AUG code for methionine in eukaryotes and archaea and N-formyl methionine in bacteria, mitochondria and plastid. •GUG codes for the amino acid valine
  • 13. TERMINATION CODON • Three codon—-UAA, UAG, UGA are termination codon that specify polypeptide chain termination . • Often referred to as Ochra, Amber and Opal codon. • These codon are recognised by Protein release factor, rather than tRNAs. •Prokaryots contain two release factors Rf-1 and Rf-2. •Rf-1 terminates polypeptide in response to codon UAA and UAG whereas RF-2 causes termination at UAA and UGA codons. • Eukaryotes contain a single release factor that recognizes all three termination codons.
  • 14. ANTICODON ● The ANTICODON is a specific sequence of three nucleotides in a transfer RNA (tRNA) molecule that is complementary to a corresponding codon in messenger RNA (mRNA). ● The codon-anticodon interaction is a key step in the process of translation during protein synthesis. FEATURES • Written in 3-5` direction. • it help in bringing a particular amino acid at its proper position during translation • always present in RNA and never in DNA.
  • 15. 1) Triplet nature 2) Degenarcy 3) Non-overlapping 4) Universal 5) Commaless 6) Non-ambiguous 7) Polarity CHARACTERISTICS OF GENETIC CODE
  • 16. 1) THE CODE IS TRIPLET → Singlet and doublet codes and not adequate to code for 20 amino acid; therefore, it was pointed out that Triplet code is the maximum required → The Triplet code has 64 codon which is sufficient to code for 20 amino acid and also for start and stop Signal in the synthesis of polypeptide chain → In a Triplet code three RNA bases code for one amino acid
  • 17. 2) THE CODE IS DEGENERATE/ REDUNDANT →the occurrence of more than one codon per amino acid is called degeneracy. • One amino acid (isoleucine) by 3 codon. • Five amino acid by 4 codon each. • Two amino acid by 6 codon each. •Nine amino acid are coded by 2 codon each → This multiple system of coding is known as Degenerate or redundant code system. Exception →Only two amino acid viz, Tryptophan and methionine are coded by one amino acid each.
  • 18. DEGENERATE AND ORDERED CODE The degeneracy in the genetic code is not at random instead it is highly ordered.Degeneracy is primarily of two types > Partial Degeneracy Ocuur when the first two nucleotides are identical but the third nucleotide of the degenerated codon differ. eg UUU and UUC code for Phenylalanine. > Complete Degeneracy. Occur when any of the 4 bases can take third position in codon and still code for the same amino acid. Eg. UCU, UCC, UCA, UCG all code for serine. Scientists have speculated that the order in the genetic code has evolved as a way of minimizing mutational lethality. Many base substitutions at the third position of codons do not change the amino acid specified by the codon. Moreover, amino acids with similar chemical properties (such as leucine, isoleucine, and valine) have codons that differ from each other by only one base.
  • 19. 3) THE CODE IS NON-OVERLAPPING →A non-overlapping code means that the same latter is not used for two different codon → In other words , no single base can take part in the formation of more than one codon → The adjacent code doesn't overlap. e.g There are bases , CATGAT → Non-overlapping code : 2 i.e CAT and GAT → Overlapping code :4 i.e CAT, GAT , ATG, TAT
  • 20. 4) THE CODE IS UNIVERSAL → The genetic code is nearly Universal. →University of Codon means that the same sequence of 3 bases encode the same amino acids in all life forms from simple microorganism to complex, multicelled organism such as human being. → the codon have same meaning in all living organisms → However, some exception have been found.
  • 21. ● 5) THE CODE IS COMMALESS → There is no signal to indicate the end of one codon and the beginning of the next. → In other words , the Codon is continuous and there are no demarcation lines between Codon
  • 22. 6) THE CODE IS NON-AMBIGUOUS → Non-ambiguous code means that there is no ambiguity about a particular codon → A particular codon will always code for the same amino acid. → While the same codon will no code for two or more different amino acid. → In case of ambiguous code , one codon should code fro more than one amino acid. In the genetic code there is no ambiguity.
  • 23. 7) THE CODE HAS POLARITY → The code is always read in the fixed direction i.e in the 5 →3’ direction → If the code is read in opposite direction (i.e 3→5) ,it would specify 2 different proteins, since the code will have reserved base sequence.
  • 24. WOBBLE HYPOTHESIS →WOBBLE means to SWAY or MOVE UNSTEADILY. → HISTORY: hypothesis proposed by Francis Crick in 1966 to explain the observed Degeneracy in the third position of a codon. →According to The Wobble Hypothesis, only the first two bases of the codon have a precise pairing with the bases of the anticodon of tRNA, while the pairing between the third bases of codon and anticodon may Wobble. Statement Wobble hypothesis states that the genetic codes are degenerate. It explains that the third base pairing varies with respect to the base at the third position like U may pair with A or G. →The phenomenon permits a single tRNA to recognize more than one codon Therefore, although there are 61 codons for amino acids, the number of tRNA is far less (around 40) which is due to wobbling.
  • 25.
  • 26. SIGNIFICANCE OF WOOBLE HYPOTHESIS →Wobble base pairs are fundamental in RNA secondary structure and are critical for the proper translation of the genetic code. →Wobbling allows faster dissociation of tRNA from mRNA and also protein synthesis →The existence of wobble minimizes the damage that can be caused by a misreading of the code; for example, if the Leu codon CUU were misread CUC or CUA or CUG during transcription of mRNA, the codon would still be translated as Leu during protein synthesis.
  • 27.
  • 28. BIOLOGICAL SIGNIFICANCE OF DEGENERACY OF GENETIC CODE ● If the code were not degenerate, 20 code would specify 20 amino acid and 44 would lead to chain termination ● he probability of mutating chain termination would therefore be much higher with a non degenerate codon MUTATIONS AND GENETIC CODE ● Mutations results in change of nucleotide sequence in DNA and RNA ● Effect of mutation is on translation through alteration in Codon ● Some mutations are harmful. ● Some of them are ● > Point mutations → Silent, misense and nonsense ● > Frame Shift mutations.
  • 29. MUTATIONS AND GENETIC CODE ● POINT MUTATION →The replacement of one base pair by another results in point mutations ● SILENT MUTATION →There are no detectable effects in silent mutation.
  • 30. MIS SENSE MUTATION → The changed base may code for a different amino acid MUTATIONS AND GENETIC CODE NONSENSE MUTATION→ The codon with altered base may become termination ( or nonsense) codon
  • 31. MUTATIONS AND GENETIC CODE ● FRAME SHIFT MUTATION → these occur with one or more base pair is inserted in or deleted from DNA