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Genetic Code features, degeneracy, and Wobble hypothesis

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"genetic code" AND wobble

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Genetic code: main features

The genetic code is the set of rules by which an mRNA nucleotide sequence is translated into an amino-acid sequence during protein synthesis.
  • Triplet code: Each codon contains 3 mRNA bases. With four bases (A, U, G, C), this gives (4^3 = 64) possible codons.
  • 61 sense codons specify the 20 standard amino acids.
  • 3 stop codons: UAA, UAG, UGA terminate translation and do not encode an amino acid.
  • Start codon: Usually AUG, which codes for methionine. In bacteria it initiates with formyl-methionine.
  • Unambiguous/specific: A given codon specifies only one amino acid. For example, UGG always specifies tryptophan.
  • Degenerate/redundant: Several different codons may encode the same amino acid.
  • Nonoverlapping: A base is part of only one codon in a given reading frame. For example, AGCUGG is read as AGC | UGG, not overlapping groups.
  • Commaless/continuous: Codons are read successively without separators or punctuation.
  • Nearly universal: The code is shared by almost all organisms, with limited exceptions, notably some mitochondrial codons. For example, mitochondrial UGA can encode tryptophan rather than stop. Biochemistry, 8th ed Lippincott Illustrated Reviews, pp. 1234-36.
  • Colinear: The order of codons in mRNA corresponds to the order of amino acids in the protein.

Degeneracy of the genetic code

Degeneracy means that one amino acid can be specified by more than one codon, while each individual codon still has only one meaning.
Examples:
Amino acidCodons
MethionineAUG only
TryptophanUGG only
PhenylalanineUUU, UUC
GlycineGGU, GGC, GGA, GGG
ArginineCGU, CGC, CGA, CGG, AGA, AGG
Most synonymous codons differ at their third base. For example:
  • UCU, UCC, UCA, UCG, AGU, AGC all code for serine.
  • A mutation UCA → UCU still gives serine, so it is often a synonymous (silent) mutation.
Degeneracy can reduce the chance that a single-base substitution changes the amino acid sequence, though synonymous mutations can still sometimes affect splicing, mRNA stability, translation rate, or protein folding.

Wobble hypothesis

Francis Crick proposed the wobble hypothesis to explain why cells need fewer tRNA species than the 61 amino-acid-specifying codons.

Where wobble occurs

mRNA codon and tRNA anticodon bind in an antiparallel manner:
mRNA codon:      5′ - N1  N2  N3 - 3′
tRNA anticodon:  3′ - N1′ N2′ N3′ - 5′
  • The first two bases of the codon pair strictly by Watson-Crick rules:
    • A-U
    • G-C
  • The third base of the codon, at its 3′ end, pairs with the first base at the 5′ end of the anticodon.
  • This final pairing is less strict and may use non-standard pairing. This flexibility is called wobble.
Biochemistry, 8th ed Lippincott Illustrated Reviews, pp. 1251-53.

Common wobble pairing rules

5′ base of tRNA anticodon3′ base(s) recognized in mRNA codon
CG
AU
UA or G
GC or U
Inosine (I)U, C, or A
Thus, one tRNA can recognize several codons that differ mainly in the third base.

Example

A tRNA with anticodon 3′-CCU-5′ can pair with both glycine codons:
mRNA: 5′-GGC-3′
tRNA: 3′-CCU-5′

mRNA: 5′-GGU-3′
tRNA: 3′-CCU-5′
At the wobble position, G in the anticodon can pair with either C or U in the codon.

Relationship between degeneracy and wobble

  • Degeneracy is a property of the code: multiple codons can specify one amino acid.
  • Wobble is a decoding mechanism: flexible pairing at the third codon position enables one tRNA to read multiple synonymous codons.
  • Therefore, wobble explains how cells translate a degenerate code without needing 61 distinct tRNA types.
Memory aid:
“First two bases are firm; third base can wobble.”
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