Friday, 18 December 2020

Nature of Genetic Codes

The linear sequence of bases in DNA constitutes alphabet (hereditary lettering of 4 bases - A, T, G, C) which 'codes' for another linear structure, a protein, written in another alphabet of 20 amino acids.

  All properties of protein, including its secondary and tertiary structure, are ultimately determined by chromosomal DNA, and all biological properties are in turn determined by the amino acid sequence of the proteins within an organism, through protein structure and enzyme activity.

  The term 'coding' implies the relationship between DNA and protein. By coding, the hereditary lettering carried in the four alphabet of DNA is ultimately converted into the protein languag composed of twenty letter alphabet of amino acids.

Triplet Nature of the Genetic Code : 

 The genetic message coded in m-RNA molecule is translated into the amino acid sequence of a polypeptide. During this procesa sets of three m-RNA nucleotides are read successively starting from an initiator codon, AUG, which codes for methionine, till a termination codon arrives at the site on the ribosome. 
 Since a termination codon does not code for any amino acid, the polypeptide chain synthesis stops. The termination codons are also known as non-sense codons.

  The whole sequence of m-RNA starting from the initiator codon up to the triplet preceding the termination codon is known as the reading-frame, Since the reading-frame is a continuous sequence of nucleotides , addition or deletion of a single nucleotide results in a change of the triplets from that point downstream. 

  Such an event constitutes a type of mutation known as frame- shift mutation which can be induced artificially by treatment with a mutagenic dye, like acridine. Frame-shift mutations in the coliphage T4 provide a strong evidence in support of the triplet nature of codons. 

Non-Overlapping Nature of the Code : 

 The non-overlapping nature of the genetic code means that the reading frame is read in sets of three consecutive nucleotides and that the same nucleotide is not used for the consecutive triplets. For example, the non-overlapping code reads a frame ABCDABCDA as ABC, DAB and CDA. The code been overlapping involving one nucleotide, it would have been read as ABC, CDA, ABC, CDA. 

  In that case, a single change in the nucleotide sequence would cause change in more than one amino acids because the same changed nucleotide would be used in more than one codon. Experimental determination of amino acid sequences of a normal (wild-type) protel and a mutant protein shows that a single mutational event alway causes a change of only one amino acid. Thus, it is proved that the codons are non-overlapping.

Degenerate Nature of the Code :

 Another important feature of the genetic code is its degeneracy. Hed the genetic code been absolute, then each amino acid would have been coded by a single codon. In that case, the chance of mutation would have been much greater than the rate of mutation observed in practice. 
Since most amino acids have more than one codon, (i.e. degenerate),a mutant codon may be substituted by another without 

  Thus, even if a mutation occurs, the organism may still produce nermal protein. Degeneracey therefore, should be considered as a positive attribute for the stability of the genetic make-up of an organism. It is a strength of the genetic code and not a weakness.

  A notable feature of degeneracy is that, in most codons, the third nucleotide at the 3-end of the triplet appears to be of less importance than the first two. 
For example, α-alanine has four codons, GCA, GCC, GCU and GCG, or threonine, has also four codons, ACA, ACC, ACG and ACU. The first two nucleotides are fixed, while the third position can be filled by any one of the four nucleotides. During protein synthesis, the m-RNA codons form base- pairs with the t-RNA anticodons.

  The degeneracy of the m-RNA codons assumes a special significance in this perspective. Crick proposed the wobble hypothesis to explain the relationship between codons and anticodons. According to this hypothesis, the third base of the degenerate codons can form non-standard base pairing with a base in the anticodon. Standard base-pairing relationship is between A and U, and G and C. But anticodons often contain some unusual bases, like inosine, pseudo-uracil etc. 

Universality of the Genetic  Code :

 Analysis of the sequence of nucleotide s of m-RNA and of amino acids of proteins of different organisms has adduced evidence in favour of universality of the genetic code which means that the same codons stand for the same amino acids in all organisms irrespective of their taxonomic position. Although this is largely true, some exceptions have been discovered which prove that the genetic code is not absolutely universal. 

  The most notable exceptions are the mitochondrial codons Mitechondria have their own DNA which is transcribed and translated to produce proteins the mitochondrial genetic codes which are different from the universal codons are presented in Table. 
Table : Differences in genetic codes of mitochondria and organisms 

  Apart from those mentioned in Table, in the mitochondria of maize (Zea mays) the codon CGG codes for tryptophan, while this codon stands for arginine in the universal code. Also, it should be noted that tryptophan is coded by UGA in the mitochondria of mammals, Drosophila and yeast. 
Thus, mitochondrial codons are not uniform in all organisms. Maize mitochondria use the codons AGA and AGG for arginine, like the yeast mitochondria.

   In more recent times, deviations of the universal code have also been discovered in some organisms. For example, in Mycoplasma capricoleum, tryptophan is coded by the codon UGA, as in mitochondria, whereas in the universal genetic code, it is one of the termination codons. In the eukaryotic protozoan Tetrahymena UAA codes for glutamine and not for termination. Probably, more such discrepancies would be revealed in future, challenging the concept of universality of the genetic code.


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