Wobble hypothesis
The wobble base pair (Engl. Wobble wobble to German wobble bases hypothesis ) is an explanation for the observation that the genetic code is a degenerate code and not more than 41 different tRNAs exist in a cell. The hypothesis was formulated by Francis Crick in 1966 .
Problem
With the four bases adenine (A), cytosine (C), guanine (G) and uracil (U), 64 different triplets can be formed. Three of these triplets are interpreted as a stop signal during translation , the remaining 61 encode amino acids . However, since there are only 21 amino acids (including selenocysteine ), an amino acid can be encoded by different codon triplets (see: Genetic Code ). For example, six different triplets code for the amino acid serine .
Since the different codons for the same amino acid usually actually occur in the genome (see also: Codon Usage ), different tRNAs should actually be present for all 61 triplets, all of which have different anticodons , but sometimes have the same amino acid. However, it has been found that, depending on the organism, only up to 41 different tRNAs exist in a cell. Consequently, some of these 41 tRNAs must be able to bind to different triplets.
Solution through the wobble hypothesis
The triplets that code for the same amino acid often only differ in their third base. For example, the triplets 5'-UCC-3 'and 5'-UCU-3' both encode serine . The tRNA with the anticodon 3'-AGG-5 'can now bind to both triplets, which in one of the two cases leads to the unusual base pairing G-U. In order for these pairings to be possible, the bases have to "wiggle out" of their position on the ribosome during translation. These pairings are therefore called wobble pairings .
Only the last base is affected by the wobble pairing, that is, the one in the 3 'direction on the mRNA or complementarily in the 5' direction on the tRNA. The first and second base always form the usual Watson-Crick pairings (A – U and G – C):
tRNA tRNA 3’–AGG–5’ 3’–AGG–5’ ||| oder ||| 5’–UCC–3’ 5’–UCU–3’ mRNA mRNA
A special example is the base hypoxanthine (I, named after the associated nucleoside inosine ), which usually does not appear in mRNA or DNA. To do this, it can be built into tRNAs at the wobble position and enable binding to adenine, uracil and cytosine. The tRNA with the anticodon 3'-UAI-5 'can therefore bind to the mRNA triplets 5'-AUA-3', 5'-AUU-3 'and 5'-AUC-3', all of which code for isoleucine .
The following base pairings are possible according to the wobble hypothesis:
3. Base of the mRNA codon | corresponding base of the tRNA anticodon |
---|---|
G | C. |
U | A. |
A, also G | U, Ψ |
C, also U | G |
U, C, or A | I. |
A tRNA can thus be bound to different codon triplets. Different tRNAs are not required for all 61 amino acid-coding mRNA codons. In fact, there are usually only 30 to 41 different tRNA molecules in the various organisms (31 in humans, 22 in mitochondria ). The significance of the wobble base can lie in a compromise between speed and safety in protein synthesis .
The following table shows some examples of tRNAs that can bind to different mRNA codons according to the wobble hypothesis:
amino acid | Codon of the mRNA | Anticodon of the tRNA | |
---|---|---|---|
Alanine | tRNA ala | 5'-GCx-3 ' with x = A, U, or C |
3'– CGI – 5 ' |
Cysteine | tRNA cys | 5'– UGx – 3 ' with x = U or C |
3'– AGA – 5 ' |
Methionine (in E. coli ) | tRNA met | 5'– AUG – 3 ' | 3'-UA C + -5 ' |
Phenylalanine | tRNA phe | 5'-UUx-3 ' with X = U or C |
3'-AA G m -5 ' |
Serine | tRNA ser | 5'-UCx-3 ' with x = A, U or C |
3'-AG I -5 ' |
Tyrosine | tRNA tyr | 5'– UAx – 3 ' with x = U or C |
3'– A Ψ G – 5 ' |
Valine | tRNA val | 5'-GUx-3 ' with x = A, U or C |
3'-CA X -5 ' |
Individual evidence
- ↑ Crick, FHC (1966): Codon-anticodon pairing: the wobble hypothesis. In: J. Mol. Biol. 19 (2): 548-555. PMID 5969078 PDF .
- ^ Nobelprize.org: Wobble in the Genetic Code
- ↑ Pseudouridine can in principle pair with all other bases (ACTU). Elzbieta Kierzek et al .: The contribution of pseudouridine to stabilities and structure of RNAs , in: PubMed Nucleic acids research 42, December 2013, DOI: 10.1093 / nar / gkt1330 .
- ↑ Florian Horn et al .: Human Biochemistry , 3rd edition, Thieme Verlag, Stuttgart 2005, ISBN 3-13-130883-4 , p. 287.