Notes on the Genetic Code

The below mentioned article provides short notes on the genetic code.

The DNA carries the genetic information for the type of protein to be synthesized. The genetic information is transmitted to the ribosomes which is the place of protein synthesis through mRNA which moves from the nucleus to the cytoplasm.

The mRNA is formed from the DNA or part of DNA which contains the information for amino acid sequence of protein to be made. This is known as transcription. With the help of tRNA in the cytoplasm, which is also produced from specific parts of DNA, the mRNA directs the information of protein by determining the exact sequence of amino acids in the protein. This is called Translation.

Now the question is where does the genetic information lie. It lies in the 4 bases occurring in large numbers in the molecule of DNA. That is, the 4 bases of the DNA molecule keep the genetic information for the structure of protein in a coded form. This is known as Genetic code.

But again there is a problem. How can these four bases control the sequence of twenty two amino acids? There are twenty two amino acids and there are polypeptides with all twenty two amino acids in a variety of combinations.

If each base has the capacity to select or attract one specific amino acid, then peptides containing only four amino acids will result. But this is not enough. If, however, a relation is assumed to be combination of two bases for each amino acid, sixteen combinations are possible. But even this is not enough. If the units, each contain three bases, then 64 combinations may be formed which are more than enough for twenty two amino acids. This is known as Triplet code.

Since the RNA carries the message in a coded form to the site of protein synthesis, it is known as messenger RNA. George Gamov first proposed the coding scheme in 1954. The bases on the mRNA were read three at a time, and each group correspond to a particular amino acid. Such a group is called a codon. Gamov, however, concluded that adjacent codons overlap.

If this were true, then:

(i) Only certain amino acids can follow others and

(ii) A change in a single base leads to a change in three adjacent amino acids. But recent evidences show no restriction on amino acid sequence and single amino acid can be changed. For this a non-overlapping code was proposed. That is, adjacent amino acids are coded by adjacent codons which did not overlap.

Although at present, three base codon or triplet code concept was generally accepted by all, the fact that there were sixty four possible triplets and only twenty two amino acids has raised the problem before the investigators. Since there are only twenty two amino acids, twenty two triplets would, therefore, seem sufficient to code the different amino acids. But the question arises as why the rest forty four triplets are there?

The suggestion was made by Crick and others that perhaps two or more triplets stand for each amino acid or that some triplets have nothing to do with amino acid but serves some other purposes. They could indicate the beginning or end of a portion of the genetic message. But whatever may be their purpose, triplets that do not represent an amino acid are some time referred to as nonsense triplets or nonsense code.

Nirenburg and Ochoa (1963) established most of the codon sequence by using radioactively labelled amino acids and the synthetic mRNA. Another method for the recognition of codons was designated by Nirenburg and Leder (1965). They prepared artificial mRNA from the base uracil and guanine in the proportion of two of uracil and one of guanine. From this they obtained three combinations CUU, UGU and UUG.

Again using a system containing tRNA, radioactively labelled amino acids and enzymes, they were able to show that only GUU codes for the amino acid Valine. H.G. Khorana (1966) synthesized the triplets of known sequences of bases and used in the cell free protein synthesis. Polypeptide having predetermined amino acid sequences were fabricated with the help of codons contained in synthetic DNAs by using the same experiment.

Consequently, Khorana’s work opened up the possibility of synthesizing DNAs having gene function. For this remarkable work Khorana, Holley and Nirenburg were awarded Nobel prize in 1968. The results of their work led to the unraveling of the genetic dictionary or genetic code for 20 amino acids as given under-

Ala=Alanine

Asp=Aspartic acid

Glu=Glutamic acid

Iso=Isoleucine

Meth=Methionine

Ser=Serine

Tyr=Tyrosine

Arg=Arginine

Cys=Cysteine

Gly=Glycine

Leu=Leucine

Phe=Phenylalanine

Thr=Threonine

Glu=Glutamine

Val=Valine

Asn=Asparagine

His=Histidine

Lys=Lysine

Pro=Proline

Trypto=Tryptophan

* Non-sense or stop codon