Genetic code and its characteristics

The pathway of protein synthesis is called Translation because the language of the nucleotide sequence on mRNA is translated into the language of an amino acid sequence. The process of Translation requires a Genetic code, through which the information contained in the nucleic acid sequence is expressed to produce a specific sequence of amino acids.

• The letters A, G, T, and C correspond to the nucleotides found in DNA. They are organized into codons.
• The collection of codons is called Genetic code.
• For 20 amino acids, there should be 20 codons.
• Each codon should have 3 nucleotides to impart specificity  to each of the amino acids for a specific codon
• 1 Nucleotide-   4 combinations
• 2 Nucleotides- 16 combinations
• 3 Nucleotides- 64 combinations ( Most suited for 20 amino acids).

Genetic code

• Genetic code is a dictionary that corresponds with the sequence of nucleotides and a sequence of Amino Acids.
• Words in dictionary are in the form of codons
• Each codon is a triplet of nucleotides
• 64 codons in total and three out of these are Non-Sense codons (Figure-1)
• 61 codons for 20 amino acids.

Figure-1- Genetic code is a dictionary that corresponds with the sequence of nucleotides and sequence of Amino Acids.

Genetic Code-Characteristics (Table-1)

1) Specificity

•  Genetic code is specific (Unambiguous)
• A specific codon always codes for the same amino acid.
•  e.g. UUU codes for Phenyl Alanine, it cannot code for any other amino acid.

2) Universal

• In all living organisms, Genetic code is the same.
• The exception to universality is found in mitochondrial codons-
• where AUA codes for Methionine and UGA for tryptophan, instead of termination codon respectively of cytoplasmic protein-synthesizing machinery.
• AGA and AGG code for Arginine in the cytoplasm but in mitochondria, they are termination codons.

3) Redundant

• Genetic code is Redundant, also called Degenerate.
• Although each codon corresponds to a  single amino acid a single amino acid can have multiple codons.
• Except for Tryptophan and Methionine, each amino acid has multiple codons.

4) Non-Overlapping and Non-Punctuated

• All codons are independent sets of 3 bases.
• There is no overlapping,
• A codon is read from a fixed starting point as a continuous sequence of bases, taken three at a time.
• The starting point is extremely important and this is called the Reading frame.

5) Non Sense Codons

• There are 3 codons out of 64 in genetic code that do not encode for any Amino Acid.
• These are called termination codons or stop codons or nonsense codons.
• The stop codons are UAA, UAG, and UGA.
• They encode no amino acid.
• The ribosome pauses and falls off the mRNA.

6) Initiator codon

• AUG is the initiator codon in the majority of proteins
•  In a few cases, GUG may be the initiator codon
• Methionine is the only amino acid specified by just one codon, AUG.

Table-1- Characteristics of Genetic code (Summary)

S.No.	Feature	Details
1.	Specific/ Unambiguous	Given a specific codon, only a single amino acid is indicated.
2.	Universal	In all living organism, Genetic code is the same (Except mitochondrial codons)
3.	Redundant/ Degenerate	Multiple codons can decode the same amino acid
4.	Non-Overlapping	The reading of the genetic code during the process of protein synthesis does not involve any overlap of codons
5.	Non-Punctuated	Once the reading is commenced at a specific codon, there is no punctuation between codons, and the message is read in a continuing sequence of nucleotide triplets until a translation stop codon is reached.

Wobbling phenomenon

• The rules of base pairing are relaxed at the third position, so that a base can pair with more than one complimentary base (Table-2)
• Some tRNA anticodons have Inosine at the third position.
• Inosine can pair with U, C, or A.  This means that we don’t need 61 different tRNA molecules, only half as many are required (Table-2)
•  First two bases in Codon in m RNA(5’-3’) base pair traditionally with the 2 nd and 3^rd base of the Anticodon in t RNA(5’-3’)
• Nontraditional base pairing is observed between the third base of the codon and 1st base of the anticodon.
• The reduced specificity between the third base of the codon and the complementary nucleotide in anticodon is responsible for  wobbling (Table-2)
• Proline has 4 codons(5’-3’CCU, CCC, CCA, CCG)
• The first three codons can be recognized by a single t RNA having  Inosine in the first place. (IGG- 5’-3’)

Table-2- Showing traditional and nontraditional base pairing between codon and anticodon.

t RNA (first base) Anticodon	m RNA (Third base) Codon	Base pairing
C	G	Traditional
A	U	Traditional
U	A	Traditional
U	G	Nontraditional
G	C	Traditional
G	U	Nontraditional
I	U	Nontraditional
I	C	Nontraditional
I	A	Nontraditional

Clinical Significance- Mutations can be well explained using the genetic code.

A) Point Mutations

1) Silent- Single nucleotide change-A to G (figure-2) same amino acid is incorporated. Mutation  goes unnoticed.

Figure-2- Silent mutation – same amino acid is incorporated due to degeneracy of the genetic  code

2) Missense-Single nucleotide changes A to C – different amino acid incorporated (figure-3). Loss of functional capacity of protein.

Figure-3- Single nucleotide change leads to the incorporation of different amino acids with the resultant synthesis of faulty protein.

3) Nonsense-Single nucleotide change from C to T, stop codon is generated (In m RNA   represented by UAG) (figure-4) , there is the premature termination of the chain, may be incompatible with life.

Figure-4- Single nucleotide change causing premature termination of the growing polypeptide chain.