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GENETIC CODE

Acorrelation exists between sequences of nucleotides in DNA (or mRNA) and amino acids in the proteins synthesized, and this relationship is called ‘Genetic Code (Fig. 9.1).

Fig.9.1

Fig. 9.1 The genetic code.

Since, DNA is made up of only four types of nucleotides (A, T, C and G) whereas proteins contain 20 types of amino acids, therefore, one-letter (4 × 1 = 4 possible codons) or two-letter (4 × 4 = 16) codes would not be enough to unambiguously encode 20 amino acids.

U

C

A

G

Singlet genetic code

U

C

A

G

First Letter

Second

Letter

U

UU

CU

AU

GU

 

C

UC

CC

AC

GC

A

UA

CA

AA

GA

G

UG

CG

AG

GG

 

2nd base

U

C

A

G

1st base

U

UUU PhenylalanineUUC PhenylalanineUUA Leucine

UUG Leucine

UCU SerineUCC SerineUCA Serine

UCG Serine

UAU TyrosineUAC TyrosineUAA Ochre (Stop)

UAG Amber (Stop)

UGU CysteineUGC CysteineUGA Opal (Stop)

UGG Tryptophan

UCA

G

3rd base

C

CUU LeucineCUC LeucineCUA Leucine

CUG Leucine

CCU ProlineCCC ProlineCCA Proline

CCG Proline

CAU HistidineCAC HistidineCAA Glutamine

CAG Glutamine

CGU ArginineCGC ArginineCGA Arginine

CGG Arginine

UCA

G

A

AUU IsoleucineAUC IsoleucineAUA Isoleucine

AUG Methionine

Start

ACU ThreonineACC ThreonineACA Threonine

ACG Threonine

AAU AsparagineAAC AsparagineAAA Lysine

AAG Lysine

AGU SerineAGC SerineAGA Arginine

AGG Arginine

UCA

G

G

GUU ValineGUC ValineGUA Valine

GUG Valine

GCU AlanineGCC AlanineGCA Alanine

GCG Alanine

GAU Aspartic acidGAC Aspartic acidGAA Glutamic acid

GAG Glutamic acid

GGU GlycineGGC GlycineGGA Glycine

GGG Glycine

UCA

G

Triplet genetic code.

Fig. 9.2 Singlet, doublet and triplet genetic codes.

Therefore, a triplet code, based on three nucleotides can give rise to 4 × 4 × 4 = 64 codons (a consequence of 3 nucleotides on mRNA is called a codon) that can code for 20 amino acids (Fig. 9.2).

The genetic code was discovered in 1960s through significant contributions of M.W. Nirenberg, J.H. Matthei, Hargobind Khorana, etc. For their work, Hargobind Khorana, M.W. Nirenberg and Robert Holley got Nobel Prize in 1968.

Hargobind Khorana (Fig. 9.3) used synthetic RNA homopolymers (e.g. poly U gave poly phenylalanine peptide, poly C gave poly proline peptide and poly A gave poly lysine peptide) and copolymers (e.g., poly UA, AC, etc.) to synthesize proteins. In this way, he could be able to assign a number of amino acids to their specific triplet codons. Thus, with homopolymers he found that:

UUU codon codes for phenylalanine,

CCC codon codes for proline,

AAA codon codes for lysine.

In this experiment, since, Poly G attained secondary structure therefore, it did not give any polypeptide.

M.W. Nirenberg and P. Leder (1964) used synthetic RNAs or codons for binding with radioactively labeled amino acids (one at a time) and passing the mixture (ribosome, codonn, AAn-tRNAn) through a nitrocellulose membrane. After autoradiography (exposure of photographic film by putting it over nitrocellulose membrane in dark), they assigned most of the codons to their amino acids whenever the radioactivity was detected over nitrocellulose membrane due to the formation of complex, ribosome-codonn-AAn-tRNAn and its retention over nitrocellulose membrane due to its larger size (when the labeled amino acid corresponded to its specific codon). Radioactivity could not be detected over nitrocellulose membrane in those situations when the labeled amino acids did not match the added codons and the smaller sized radioactive AAn-tRNAn passed through the nitrocellulose membrane. This experiment was performed for all the 20 types of labeled amino acids (one at a time) and the genetic code dictionary was deciphered (Fig. 9.4 and 9.5).

Fig.9.3

Fig.9.4

Fig.9.5

Fig 9.5 Codon-anticodon binding for amino acids, serine (left) and tryptophan ( right).

Out of these 64 codons on mRNA, 61 codons specify 20 types of amino acids in which two are initiation codons (AVG and GVG) and three are termination codons (UAA, VAG and UGA). Whenever, any of the three termination codons is encountered on mRNA at the A-site of ribosome, synthesis of protein chain terminates, as no tRNA (with an amino acid) can recognize these termination codons and the polypeptide chain separates from the ribosome.

Characterstics of Genetic Code                                                                                    }

 

1.Triplet Code: Each codon is made up of three successive nucleotides in mRNA that specifies an amino acid in the polypeptide.

2.Universal Code: The genetic code is applicable universally, e.g., it is same from lower

organisms, like viruses to higher organisms, like human being.

Exceptian: A different and more primitive genetic code is found in the mitochondria of
some eukaryotes.

3.Comma-less Code: The sequences of codons in mRNAs are always continuous and pauses are not found in between the two adjacent codons. Thus, after one amino acid by a codon, the second amino acid is automatically coded by the next 3 nucleotides (codon) and no letters (nucleotides) are wasted for telling that one amino acid has been coded and now the second should be coded.

Thus, a 30 amino acid long polypeptide is specified by a sequence of 90 nucleotides long mRNA.

4.      Non-overlapping code: The codons in a mRNA are found to be non-overlapping and a base in mRNA is not used for two adjaced codons. (Fig 9.6)

Fig.9.7

Fig. 9.7 Overlapping genes in virus ɸX174.

In the virus ɸX174, that has single-stranded genomic DNA, though the genes are overlapping, but this overlapping occurs at different time and space (Fig. 9.7). Thus, in this virus inspite of overlapping genes, the genetic code is non-overlapping.

5.Unambiguous Code: It means, one codon always represents its specific one amino acid only and has no double meaning, e.g., the codon UUU always codes for the same amino acid, phenylalanine and not for any other amino acid.

Exception: The codon GUG is normally meant for the amino acid valine, but sometimes
it is also used as the initiation codon (at first position or 5′ end in mRNA) coding for the
amino acid methionine (or formyl methionine).

6.Degenerate Code: In a triplet genetic code, out of 64 possible codons, all codons have some meaning. In a cell of an organism, there are 20 types of amino acids and 61 types of codons coding for various amino acids (and 55 types of tRNAs). Thus, one amino acid can have more than one codons (called synonymous codons) that can be recognized by the same tRNA molecule. In these synonymous codons, the first and second nucleotides remain the same, whereas, the third nucleotide can be different. Thus, the pairing of the anticodon in the same tRNA with the synonymous codons is allowed due to wobbling (un stability) in 3′ base of synonymous codons (in mRNA) and 5′ base of anticodon (in tRNA).

For example, the two synonymous codons for phenylalanine differ in the 3′ base, whereas, the
other two 5′ bases remain the same (3rd base degeneracy). Thus, often the 3′ base of the synonymous is not important and this reduced specifity is called 3rd base degeneracy.

Fig.9.8

Fig.9.8 Synonymous codons for phenylalanine.

In a cell of an organism, there are 55 types of tRNAs, 20 types of amino acids and 61 types of codons coding for various amino acids. Thus, one amino acid can have more than one codons called synonymous codons) that can be recognized by the same tRNA molecule. Only Tryptoplan and methionine have only one codons, all other amino acids are specified by 2-6 synonymous codons.

QUESTIONS

1.      What is genetic code? Describe its general properties. 

2. Describe an experiment which helped in deciphering the genetic code.

                                                    or

Discuss an experiment conducted by Hargobind Khorana and workers (et. at.) for codon assignments.

3.    Write short notes on frame-shift mutations and their role in understanding the genetic code.

 or

Give some evidences which support that genetic code does exist in living systems.

4.Write short notes on

I.        Synonym codons

II.       Wobble hypothesis

III.      Initiation and termination codons.