Table of Contents -
Wobble Hypothesis
Wobble Hypothesis was proposed by Francis Crick in 1966.
Wobble Hypothesis states that, only the first two bases of the codon of mRNA have a precise pairing with the bases of an anticodon of tRNA, while the pairing between the 3rd base of codon of mRNA and anticodon of tRNA may wobble or show wobble base pairing.
Due to wobble base pairing, a single tRNA can recognize more than 1 codon. This can be proved from the below fact :-
There are total 61 codons for 20 standard amino acids but number of tRNAs are only about 40. This means that, 1 tRNA can recognize more than 1 codon and this is possible only because of wobble base pairing.
Rules for Normal or Canonical Hydrogen bonding
1) IN DNA, there are 4 bases which are found namely Adenine, Guanine, Cytosine, Thymine. These bases are abbreviated as A,G,C,T respectively. Adenine and Guanine are purines, while Cytosine and Thymine are pyrimidines.
2) For Normal or Canonical Hydrogen bonding, below rule is followed :-
Purines bind complementarily to Pyrimidines or vice versa. For example, Adenine (Purine) bind complementarily to Thymine (Pyrimidine) and vice versa ; Guanine (Purine) bind complementarily to Cytosine (Pyrimidine) and vice versa.
[ But Purines will not bind complementarily to Purines ; Pyrimidines will not bind complementarily to Pyrimidines. For example, Adenine (Purine) will not bind complementarily to Guanine (Purine) ; Cytosine (Pyrimidine) will not bind complementarily to Thymine (Pyrimidine) ]
3) Adenine (Purine) bind to Thymine (Pyrimidine) by forming 2 hydrogen bonds whereas Guanine (Purine) bind to Cytosine (Pyrimidine) by forming 3 hydrogen bonds.
4) IN RNA, there are 4 bases which are found namely Adenine, Guanine, Cytosine, Uracil. These bases are abbreviated as A,G,C,U respectively. Adenine and Guanine are purines, while Cytosine and Uracil are pyrimidines.
5) For Normal or Canonical Hydrogen bonding, below rule is followed :-
Purines bind complementarily to Pyrimidines or vice versa. For example, Adenine (Purine) bind complementarily to Uracil (Pyrimidine) and vice versa ; Guanine (Purine) bind complementarily to Cytosine (Pyrimidine) and vice versa.
[ But Purines will not bind complementarily to Purines ; Pyrimidines will not bind complementarily to Pyrimidines. For example, Adenine (Purine) will not bind complementarily to Guanine (Purine) ; Cytosine (Pyrimidine) will not bind complementarily to Uracil (Pyrimidine) ]
6) Adenine (Purine) bind to Uracil (Pyrimidine) by forming 2 hydrogen bonds whereas Guanine (Purine) bind to Cytosine (Pyrimidine) by forming 3 hydrogen bonds.
[ But for RNA, important point to remember is that, Adenine (Purine) binds weakly with Uracil (Pyrimidine) with 2 Hydrogen bonds ]
Rules for Wobble Base Pairing or Non-Canonical Hydrogen Bonding
- A of mRNA can bind with U,I anticodon of tRNA
- C of mRNA can bind with G,I anticodon of tRNA
- G of mRNA can bind with C,U anticodon of tRNA
- U of mRNA can bind with A,G,I anticodon of tRNA
[tRNA has additional Purine nucleoside namely Inosine (I) which is formed upon deamination of adenosine by adenosine deaminase enzyme. Inosine is formed when hypoxanthine is attached to a ribose ring (also known as ribofuranose) via a Beta-N9-glycosidic bond]
Wobble Phenomenon
1st and 2nd base of codon (From 5′ end) base pair precisely with 3rd and 2nd base of anticodon (From 3′ end) respectively but base pairing between 3rd position of codon and 1st base of Anticodon is not precise i.e it can wobble.
Important thing to note is that, if the orientation of mRNA is 5′ –> 3′ , the tRNA’s orientation should be 3′ –> 5′ in order to bind complementarily as shown in below diagram.
[If above things seem confusing, see the diagram below. I am sure you will be able to understand it completely]
1 tRNA can bind to more than 1 codon due to wobble base pairing
Significance of Wobble Hypothesis
1) Fewer tRNAs are required to decode codons during translation or protein synthesis. Moreover, a single tRNA can recognize more than 1 codon which results in increased efficiency of protein synthesis.
2) Wobble base pairing results in faster dissociation of tRNA from mRNA which indirectly also helps in faster protein synthesis process.
3) Wobble phenomenon can help in protecting from point mutations or minimizing the damage associated with misreading of codons by anticodons of tRNA during protein synthesis.
Wobble base pairing also explains degeneracy of genetic code. We have studied that, 1 amino acid can be coded by more than 1 codon. For example, Glycine amino acid can be coded by GGG, GGA, GGC. If “GGG” codon is misread as GGA or GGC by tRNA during protein synthesis, still it will code for Glycine. This is how, wobble phenomenon protects from misreading the codon by tRNA or protects from point mutations [“Considering that mutation or misreading occurs at 3rd position of codon. If mutation or misreading occurs at 1st or 2nd position of codon, then wobble hypothesis cannot protect from damage associated with it”]
4) Since wobble phenomenon minimizes the damage associated with misreading of the codon by tRNA or protection from point mutations, wobble hypothesis can also likely provide evolutionary advantage due to more efficient and accurate protein synthesis while maintaining genomic integrity or stability.