Genetic code

 


Genetic Code:

Genetic information coded in DNA is passed from the nucleus to the cytoplasm through m_ RNA during protein synthesis. Proteins  have 20 amino acids which are arranged in different number and sequences to form different proteins. The information for the sequence of amino acids present in the proteins is encoded or hidden in the sequence of nucleotides present in the m_ RNA. This is present in the form of nucleotides coding for one amino acid i.e. triple  code. This is  called genetic code. If a nucleotide is capable of coding for an amino acid ( singlet code) there will be only 4 codons. If 2 bases code for an amino acid there will be only 16 codons available which are not sufficient for the coding of 20 amino acids.So it was hypothesised that 3 nucleotides coded for one amino acids, so 4³( 4×4×4)  64. codon will be available for 20 amino acids.  This was further support by many findings.


The various observations which helped in deciphering the triplet genetic code are as follows:

1): Crick et al observed that deletion or addition of one or two base pairs in DNA  of T4 bacteriophage disturbed normal DNA functioning. But, when three base pairs were added or deleted the disturbance was minimal. 


2): Nirenberg and Mathaei argued that a single code ( i.e. one amino acid coded by one nitrogen base) can specify only 4 acids (4¹) , double code only 16 acids ( 4²) while a triple code can specify upto 64 amino acids ( 4³) . As there are 20 amino acids,  triplet code should be operative. 


3): Nirenberg prepared polymerase of the four nucleotides ___ UUUU....( Polyuridylic acid), CCCC.... (Polycytidylic acid), AAAA....( Polyadenylic acid) and GGGG.....( Polyguanylic acid). He observed that poly__ U resulted in the formation of polyphenylanaline, Poly__ C resulted in formation of polyproline while poly_ A helped to form polylysine. However, poly_ G did not function. Later on, GGG was found to code for amino acid glycine. A polynucleotide chain of DNA formed of a single type of nucleotide is known as homopolymer chain.


4): Khorana synthesised copolymers of nucleotides like UGUGUGUG ... and observed that they stimulated the formation of polypeptides having alternately similar amino acid ( e.g., UGU) and other three the second amino acid ( e.g., GUG).


               GUG     UGU    GUG   UGU    GUG
               Val____ Cys___Val___Cys___Val 

It must be remembered that the code languages of DNA and mRNA are complementary. Thus the two codons for phenylalanine are UUU and UUC in case of mRNA while they are AAA and AAG for DNA.


11 characteristics  of Genetic code 

1): Triplet Code: Three adjacent nitrogenous bases form a coden which specifies the  placement of one  amino acid in a polypeptide. 


2): Start signal and Stop Signal:Polypeptide synthesis is signalled by two initiation codons __ AUG or GUG. The initiation codon is AUG in majority of cases and it codes for the amino acid_ methionine. Polypeptide chain termination is signalled by three termination codons__ UAA ( ochre), UAG ( amber) and UGA( opal). The names like ochre and amber are taken from the bacterial strains in which they were identified. They do not specify any amino acid and are also called nonsense  codons. The initiation and termination codons are also called punctuation codons.


3): Universal Code : The genetic code is universal,  i.e., a codon species the same amino acid from a virus to a tree or human being.


4): Nonambiguous Codons: One codon specifies only one amino acid and not any other.




5): Related Codons:  Amino acids with similar properties have related codons, e.g., aromatic amino acids tryptophan ( UGG), phenylalanine ( UUC,UUU), tryrosin ( UAC,UAU). The tendency for similar amino acids to be represented by related codons minimizes the effects of mutations. It increases the probability that a single random base change will result in no amino acid substitution or in one involving an amino acid of similar character.



6): Commaless: The genetic code  is continuous and does not show any pauses after the triplets. If a nucleotide is deleted or added, the whole genetic code will be read differently. Thus a polypeptide having 50 amino acids will be specified by a linear sequence of 150 nucleotides. If a nucleotide is added or deleted in the middle of this sequence,  the first 25 amino acids will be same but next 25 amino acids will be quite different from the ones present in the original polypeptide. This concept is explained under Frame_ shift  mutation.


7): Polarity : Genetic code is always read in a fixed direction i.e. 5' __ 3'.


8): Non_ overlapping  Code: A nitrogen base is a constituent of only one codon and never two or more.

9): Degeneracy of Code:Since there are 64 triplet codons and only 20 amino acids,  some amino acids must be coded by more than one codon. Only  tryptophan ( UGG) and methionine ( AUG) are coded by single codons. All other amino acids are coded by 2_ 6 codons. The latter are called degenerate codons. These codons, which have the same meaning,  are also called synonyms or sister codons. In  degenerate codons the first two nitrogen bases are similar while the third one is different. As the third nitrogen base has no effect on coding, the same is called wobble position.  Degeneracy of genetic codons seems to be of some advantage to the organisms as it reduces chances of mutations. One codon changing to its sister will have no effect on the organisms ( called silent mutation). 


Reasons for Degeneracy:

(i) The bases in the first position of anticoden on tRNA is commonly an unusual or abnormal base like inosine, pseudouridine or dihyrouridine.( In fact tRNA is unique nucleic acids in its  content of unusual bases) .These abnormal bases at first position of anticodon are able to base_ pair with more than one base in the third position of the codon, e.g. Inosine ( I) can pair with A, C and U 
Modifications elsewhere in the vicinity of the anticodon also influence its pairing.



(ii) Amino acyl t _ RNA synthetase enzyme may commit some mistake in the attachment of proper amino acid.


(iii) The number of trRNAs  is not necessarily as high as  the  number of codons. This means that one tRNA species can recognize  several synonymous codons meant for the same amino acid ( such codons are called synonyms). According to wobble hypothesis,  a minimum of 31 tRANs ( excluding the initiator) are required to recognize all 61 codons. Conversely, a given codon may be recognized by more that one tRNA species. Usually each amino acid is represented by more than one tRNA. Multiple  tRNAs representing the same amino acid are called isoaccepting tRNAs; because they are all recognised by the same synthetase.


10): Colinearity: Both polypeptide and DNA or mRNA show a linear arrangement of their components. The sequence of triplet nucleotide bases in DNA  or mRNA corresponds to the sequence of amino acids in the polypeptide synthesized under the guidance of the former . Change in codon sequence will produce a similar change in amino acid sequence of polypeptide. It means that the first codon of DNA or mRNA codes for the first amino acid and sixth codon codes for the sixth amino acid of the polypeptide chain and so on.If any one codon, say tenth codon is modified in mRAN, then tenth amino acid will be replaced in the polypeptide chain.




11):  Cistron__ polypeptide Parity:  A cistom ( = gene) specifies the formation of a  particular polypeptide. Thus there should be as many cistrons ( = genes) as the types of polypeptides found in the organism. 



Central Dogma:

It is the flow of information from DNA to mRNA and then decoding the information present in mRNA in the formation of polypeptide chain.


         transcription                   translation
DNA➡️➡️➡️➡️➡️➡️mRNA     ➡️➡️➡️➡️➡️                                                                                                                                    polypeptide(protein)

The four _ letter language of DNA is transcribed into 4 letter language of mRNA which is then translated in 20 letter language of protein . During transcription there is little change in genetic code except that it is complementary to genetic code of DNA and T is replaced  by U. During translation the genetic code is decoded to produce polypeptide. 


The concept of ' central  dogma'was given by Crick in 1958. It suggests unidirectional or one_ way flow of information from DNA to RNA and then to protein. Commoner propounded circular  flow of information ( from DNA➡️RNA➡️Protein ➡️RNA➡️DNA. Temind observed that retroviruses operate a central dogma reverse( = inverse flow of information) or teminism inside host cells. Genetic RNA of these viruses synthesizes DNA through  reverse transcription. This DNA transfer information  to mRNA which takes part in translation of the coded information. 

The salient features of genetic code are ad  follows:

(i) The codon is triple .61 codons code for amino acids  and 3 codons do not code for any amino acids, hence they functionas stop codons.


(ii) One codon codes for only one amino acid,  hence , it is unambiguous and specific. 


(iii) Some amino acids are coded by more than one codon, hence the code is degenerate. 



 (iv) The codon is read in mRNA in a contiguous  fashion. There are no punctuations.



 (v)The code is nearly  universal: For example, from bacteria to human UUU would code for Phenylalanine ( phe). Some exceptions to this rule have been found in mitochondrial codons, and in some protozoans. 


(vi) AUG has dual functions. It codes for Methionine ( met), and it also act as initiator codon.

If following is the sequence of nucleotides in mRNA , predict the sequence of amino acid coded by it ( take help of the checkerboard) :


_AUG UUU UUC UUC UUU UUU UUC_

Now try the opposite. 

Following is the sequence of amino acids coden by an mRNA. Predict the nucleotide sequence in the RNA: 


Met _ Phe_ Phe_ Phe_ Phe_ Phe_ Phe 



Functions

1): It is the genetic material and carries hereditary characters from parents to the young ones. This is achieved through its unique property of replication. 

2): It enables the cell to maintain, grow and divide by directing the synthesis of structural proteins.

3): It control metabolism  in the cell by directing the formation  of necessary  enzymatic proteins. 

4): It produce RNAs by transcription  for use in protein synthesis. 

5): It creates  variety  in population  by causing recombination through crossing  over.

6): It contributes to the evolution of the organism by undergoing gene mutation ( changes in the base pairs).

7): It beings about differentiation of cell during development. Only certain genes remain functional in particular  cells. This enables the cells having similar genes to assume different  structure and function.

8): It controls the postnatal development through adulthood to death by its " internal clock" .

 Genetic Code:

The particular sequence of bases  in each polynucleotide chain is known as the primary  sequence of DNA. This primary  sequence  form the genetic code, i.e. the information  required by the cell to synthesize all the specific proteins it needs.The primary sequence  of DNA shows unlimited variation, and this is the basis of huge variety  seen in the living  systems. 





  A DNA molecule include many genes, each with a specific sequence of nucleotides. A sequence AGGTAACCT codes for one protein and the sequence CGCCTTAAC codes for a different protein ( real genes are very long, may have hundreds to thousands of nucleotides).

 Sense and Missense DNA chains:The genetic information exists in the base sequence of one of the two chains of DNA molecule. This chain is often called sense chain.Its complementary chain is termed missense chain, or antisense chain. The missense chain is important in the replication of DNA molecule in cell division, but does not take part directly in transcription. It is copied from the sense chain.

 ● Noncoding DNA:Greater part of DNA in eukaryotic cells does not code for RNAs. This "extra",or  noncoding DNA seems to have no function. It has two special forms: 

(i) Repetitikus DNA:  The noncoding  DNA has many base repeated several times. The repeated sequences are collectively called repetitius DNA.

(ii) Jumping Genes:  Some repetitive DNA sequences are not found at fixed sites in the DNA of different individuals of the same species. Such " mobile" DNA segments are often referred to as " jumping genes". They cause mutations and, thus, have a role in evolution.  However, they usually have no role in the life of the individual. 

    The existence of nonfunctional DNA indicates that the eukaryotes use only a small fraction of their total DNA.

  Bacteria have little nonfunctional DNA. 

 ● Satellite DNA: Part of DNA having long stretches of repetitive base pairs is called satellite DNA. A satellite DNA having a few ( 1__ 6) base pair repeats is termed microsatellite, and that with more ( 10__60) base pair repeats is known as  minisatellite. The minisatellites are highly variable and are specific for each individual. These help in DNA matching for identification of persons. Minisatellites were first discovered by Jaffreys et al in 1985.

● Palindromes DNA:It is a part of DNA in which the base sequence of one strand is opposite to that of the other strand when read opposite directions.  DNA regions that transcribe rRNA are often palindromic. However,  the true Significanc of palindromic DNA is not clear.

  3' __C __G__G__A__A__T__T__C__C__G__5'

  5' __G__C__C__T__T__A__A__G__G__C__3'

     Human body cells normally have 46 chromosomes with a total of 1.6 billion base pairs. The DNA of 46 chromosomes of a single cell has a total length of about 2 meters. The chromosomes of a dividing cell are ten thousand times shorter this. The proteins cause the packing of DNA molecules so tightly. 




● In Vitro Synthesis  of DNA:In 1961, Kornberg and his coworkers synthesised DNA from a mixture of all the four types of deoxyribonucleoside triphosphates, DNA polymerase enzyme, metal ions and a single strand of viral DNA. The latter was separated from  its complementary strand by denaturation. It  acted as a template.




















































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