What is Genetic Code | What is Codon

Genetic code is a group or sequence of nucleotides (nitrogenous bases) in the DNA molecule. Genetic code in DNA provides instructions to produce mRNA or we can say that mRNA is formed from genetic code (sequence of nucleotides or DNA). The term 'genetic code' is given by George Gamow.

The triple nitrogenous base sequence on mRNA (which is produced from DNA through transcription) is called a codon. Whereas, genetic code refers to sequences of triplet nitrogenous bases or the entire sequence of nitrogenous bases in a DNA segment. So, genetic code is the language of DNA.

Codon will always be in triplet form as it is coding for a single amino acid. So, it is a triplet that is known as a codon. It is a set of instructions that directs the translation of DNA into amino acids, the monomers of proteins. As a codon is a group of three nucleotides, the four nucleotides can produce 64 different combinations or codons. Out of these, 61 codons code for amino acids and they are known as sense codon, whereas, the remaining 3 codons (UAA, UAG, UGA) represent stop signal for the end of protein synthesis. They are known as nonsense code or codon as they do not code for protein synthesis.

Besides this, one codon code for the synthesis of only one specific amino acids, so, it cannot code for any other amino acid. However, there are some amino acids that are coded by more than one codon.

The codon is read in mRNA in a continuous fashion, no gap between two codons. Also, the codes are non-overlapping, for example, in AUGUUU, there can be AUG, UUU, etc., but not UGU after AUG. So, the three nucleotides of AUG cannot become part of other codes or codons.

The codon AUG performs dual functions; it acts as a starting codon or initiator and also codes for the synthesis of amino acid Methionine. However, only if it is present at the start of a transcription unit, it acts as a starting codon, but, if it is present in between it will code for Methionine.

Some exceptions of Genetic Code:

• Although UAA and UGA codons act as stop or termination codons, they code for the synthesis of amino acid, glutamine in paramecium and some ciliates.
• Although, the codons AGG and AGA code for arginine, they act as stop codons in human mitochondria.
• Although UGA is a stop codon, in mitochondria it codes for tryptophan. Similarly, AUA code for methionine instead of isoleucine in the human mitochondrion.

How the genetic code discovered I Who discovered genetic code

It was the George Gamow who for the first time in the 1950s realized that the genetic code was composed of groups or triplets of three nucleotides. He concluded that a group of three consecutive nucleotides of a gene might code for one amino acid in a polypeptide or protein.

He tried to find out how 20 amino acids in the human body are synthesised by four nitrogenous bases. He made the different combination of nitrogenous bases to understand how many nitrogenous bases could be working as a group to code for a single amino acid.

For example, he said that if one nitrogenous base is synthesizing one amino acid then it can give us only four amino acids but we have 20 amino acids. Similarly, he found that there would be a total number of 16 groups or combination of nitrogenous bases if groups of two nucleotides or nitrogenous bases are made out of four available bases. He found that even a doublet code (a group of two nucleotides) for an amino acid would not work as only 16 ordered groups of doublet code or groups of nucleotides could be formed that is too few to code for the synthesis of 20 amino acids.

Next, he chose made group or combination of three nitrogen bases and found that a code made of a group of three nucleotides seemed appropriate as it would make 64 unique groups of three nucleotides or triplets (4x4x4) that would be sufficient to code for the synthesis of 20 amino acids. So, Gamow concluded that genetic code or nitrogenous bases that form codon exits in the form of a triplet (a group of 3 nitrogenous bases). And, each triplet forms an amino acid.

Gamow's triplet hypothesis was widely accepted. However, it was not clear that which triplet of nucleotide code for which amino acid.

Later, the progress in the understanding of genetic code began in 1961 with the work of the American biochemist Marshall Nirenberg. He along with his team was able to identify specific nucleotide triplets that correspond to specific amino acids. They were able to reach this conclusion through the two following experimental innovations.

• A method to make artificial mRNA with specific know sequences.
• A process to translate mRNA into polypeptides outside of a cell into a cell-free system made of cytoplasm from burst E. coli cells with all materials required for translation.

For example, Nirenberg made an mRNA molecule containing only Uracil nucleotide (poly-U). Then he added this mRNA to the cell-free system. He found that all the polypeptides made by this mRNA are made of only one amino acid, which was phenylalanine. There was only one triplet in this mRNA, which was UUU, so he concluded that UUU might have coded for phenylalanine. Similarly, he also proved that poly-C mRNA was decoded into polypeptides made of amino acid proline that suggested that the triplet CCC may code for proline.

Later, Har Gobind Khorana, a biochemist, synthesized artificial mRNA with more complex sequences. For example, he generated a poly-UC ( UCUCUCUC….) mRNA and added it into a cell-free system. Now as per the triplet code rule, this poly-UC will give two combinations of triplet codon which are CUC and UCU.

This mRNA made polypeptides with an alternating arrangement of serine and leucine amino acids. CUC formed leucine and UCU formed serine. This experiment, like other experiments, also confirmed that the genetic code is a triplet. Accordingly, as of now, codon UCU codes for serine and codon CUC codes for leucine. Later by 1965, Nirenberg, Khorana and their team members successfully deciphered the whole genetic code and came up with a genetic code table with all the 64 possible combinations of bases or 64 codons.

Types of codons:

1. Sense codons

The codons that code for the amino acid synthesis are called sense codons. There are 61 sense codons as there are 61 codons that code for 20 amino acids.

2. Signal Codons

They code for signals such as start and stop signals during protein synthesis. There are four signal codons that include AUG, UAA, UAG and UGA. They can be of following two types:

i) Start codons: As the name suggests, this codon starts the translation process. It is the first codon of a messenger RNA that marks the site at which translation starts. It is also known as the initiation codon as it initiates the synthesis of the polypeptide chain. For example, AUG is a start codon, however, it also codes for the methionine amino acid.

ii) Stop codons: It is located within the mRNA. It is required to stop the translation or synthesis of the polypeptide chain. They give the signal for the termination of the polypeptide chain, so they are also called termination codon. For example, UAA, UAG and UGA are stop codons. Formerly, they are known as non-sense codons as they don't code for any amino acids.

The signals given by stop codons are not read by transfer RNA (tRNA). They are read by proteins, which are known as release factors. In prokaryotic organisms or prokaryotic cells, the release factors are RF1, RF2 and RF3. RF1 recognizes the stop signals of UAA and UAG, whereas, RF2 catches the signals of UAA and UGA. However, the RF3 activates RF1 and RF2. Whereas, in eukaryotes, there is only one release factor (eRF1) that recognizes all of the three stop codons.

Properties of Genetic Code:

• Triplet: The genetic code is a triplet. There are a total of 64 triplets or genetic code or codons that are sufficient to code for 20 amino acids and also act as a stop and start codon to initiate and terminate the formation of the polypeptide chain, respectively.
• Universal: It is nearly universal. A specific codon code for specific amino acids and similarly specific codons work as start and stop codons in all animals, plants and organisms. For example, a codon such as UUU whether in bacteria or in humans will make Phenylalanine (phe). However, it is found that in mitochondria and in some protozoans it does not code for Phenylalanine. So, due to some exception, it is called nearly universal.
• Commaless: The code is commaless. The codons are continuous which means there is no demarcation line between two consecutive codons.
• Code is redundant: It means the genetic code is degenerate as there are more codons than required as a result three are amino acids that can be coded by multiple codons.
• Non-Overlapping: It is non-overlapping which means six bases (2 triplets) will code for two amino acids. One letter is read-only once or one nucleotide is used only once. If it were overlapping, six bases will code for more than two amino acids. For example two bases CATGAT will give two non-overlapping codes; CAT and GAT. However, if it were overlapping it would give more than two codes such as CAT, GAT, ATG and TAT.
• Non -ambiguous: Although it is redundant code, we can say that it is non-ambiguous as each codon code for only one specific amino acid under normal conditions.
• Polarity: Each codon has a polarity which means a fixed direction for the reading of the message. If a codon is read in the opposite direction it will code for a different amino acid. For example, UUG will code for leucine, whereas GUU (reading from right to left) will code for Valine. The message in mRNA is read in the 5'-3' direction, so, we can say that the polarity of the genetic code is from 5' end to 3' end.

Functions of genetic code:

• Genetic code decides the sequence in which amino acids are added to a polypeptide chain to synthesize protein.
• It is the genetic code that enables nucleotide sequences in DNA and RNA to be translated into the amino acids they code for.
• Cells decode mRNA that is formed during transcription from DNA by reading their groups of three nucleotides (codons).