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Wobble Hypothesis of Genetic Code

In this wobble hypothesis of genetic code post we have briefly explained about wobble base pairing hypothesis, degeneracy of the universal genetic code, and significance.

Francis Crick introduced the Wobble Hypothesis in 1966, explaining that the structure of the anticodon of tRNA causes the degeneracy of the genetic code. 

Only the first two bases of the codon have a precise pairing with the nucleotides of the anticodon of tRNA, according to this hypothesis, but the pairing between the third and fourth bases of the codon and anticodon may wobble base pairing (wobble means to sway or move unsteadily). 

This mechanism enables a single tRNA to recognise several codons. As a result, despite the fact that there are 61 codons for amino acids, there are only roughly 40 codons for tRNA, which is due to wobbling.

Wobble Hypothesis of Genetic Code

The anticodon is a three-base sequence on tRNA that is complementary to the mRNA codon. Each tRNA binds to a specific amino acid, but some tRNA molecules’ anticodons can bind to two or three different codons. The less restrictive 5′ base on the anticodon loop, also known as the wobble base pairing base, binds to the 3′ base on the mRNA, causing the anticodon to be flexible. 

For the decoding of the mRNA codon into an amino acid, only the first two nucleotides are strict and spatially constrained. Codons GCU, GCC, GCA, and GCG, for example, code for the amino acid alanine. This degenerate capacity requires the base’s wobbling movement in the 5′ anticodon position. Wobble base pairing hypothesis states that, base pairing restrictions are weakened at the third position, allowing a base to couple with many complimentary bases. 

The hypothesis explains why the base inosine appears in position 1 of anticodons of various tRNAs, why many mRNA codon words translate to a single amino acid, why there are far fewer tRNAs than mRNA codon types, and why the genetic code’s redundant nature translates into a precise set of 20 amino acids.

The Wobble Hypothesis

A non-Watson Crick base pairing between two nucleotides in an RNA molecule is known as a wobble base pairing. Guanine-uracil, inocine-uracil, inosine-adenine, and inosine-cytosine are the four primary wobble base pairing. 

Wobble base pairing are essential for the efficient translation of the genetic code and are found in the secondary structure of RNA. Inosine is a nucleoside that is generated when adenine is hydrolytically deaminated. 

It is structurally similar to guanine, but it lacks the 2-amino group. Inosine may form base pairs with uracil, cytosine, and adenine because it lacks the 2-amino group, making it a particularly wobbly base.

Degeneracy of the Universal Genetic Code

There will be some overlap when there are 64 codon choices for 20 amino acids (plus stop codons). There is redundancy in the genetic code, but no ambiguity. GGG, GGA, GGC, and GGU, for example, all encode the amino acid glycine, but none of them encode another amino acid. 

The third location of degenerate codons is frequently different. It is thought that the genetic code is universal. That is, both the simplest bacterial organism and humans use the same code. 

This universality is a huge plus for humanity. When a human gene is implanted in bacteria, it appears to the bacterium as a fragment of DNA. The As, Cs, Gs, and Ts of humans are identical to the As, Cs, Gs, and Ts of bacteria. As a result, the bacterial proteins will transcribe and translate this DNA, resulting in the production of a human protein.

Wobble Base Pairing and it’s Significance

1. The small number of tRNAs in human bodies, along with wobble base pairing, allows for extensive specificity. Many biological functions are accelerated as a result of this, as evidenced by the E.coli. Wobbling base pair’s thermodynamic stability is comparable to that of a Watson-Crick base pair.

2. Wobble base pairing are important in RNA secondary structure and are required for correct genetic code translation. It aids in tRNA dissociation from mRNA as well as protein synthesis.

3. The presence of wobble base pairing decreases the potential for code misreading to cause damage; for example, if the Leu codon CUU was misread as CUC, CUA, or CUG during mRNA transcription, the codon would still be translated as Leu during protein synthesis.

Further Readings

Reference

https://en.wikipedia.org/wiki/wobble base pairing

https://teaching.ncl.ac.uk/bms/wiki/index.php/wobble base pairing

https://link.springer.com/referenceworkentry/10.1007%2F978-3-642-11274-4_1692