A cell has a tRNA with inosine (I) at its wobble position. This single tRNA can decode codons ending in U, C, or A. A student concludes that inosine must therefore pair with all four standard nucleotides anywhere in the codon. What is wrong with this reasoning?
ANothing — inosine does pair with all four nucleotides at any codon position
BInosine can only pair with pyrimidines, so it cannot recognize codons ending in A
CThe relaxed pairing is specific to the third codon position (wobble position); the first two positions require standard Watson-Crick pairing, constraining which amino acid is specified
DInosine pairs with U, C, and A only when the codon is in the ribosomal A site
The critical distinction is that wobble pairing is position-specific. The first two positions of the codon are read with standard Watson-Crick geometry, which means they strictly determine which amino acid is encoded. Only the third position (the wobble position) tolerates non-standard pairings. A single tRNA with inosine at its wobble-position anticodon nucleotide can decode three codons — but those codons all specify the same amino acid, because the first two positions are identically paired. The flexibility is used to reduce the number of tRNA species needed, not to change amino acid identity.
Question 2 Multiple Choice
A mutation changes the third nucleotide of an alanine codon from GCC to GCU. The cell has a tRNA with inosine at its wobble position that normally reads GCC. What is the most likely result?
AThe mutation causes a different amino acid to be incorporated because the tRNA no longer recognizes the codon
BTranslation stalls at this codon because no tRNA matches GCU
CThe same alanine tRNA (with inosine) reads GCU as well, and the same amino acid is incorporated — the mutation is silent
DA second tRNA with a different anticodon must be recruited, doubling the translation time at this site
This is a direct consequence of wobble base pairing. Inosine at the wobble position pairs with U, C, or A, so a tRNA that reads GCC (C at the third position) also reads GCU (U at the third position) and GCA (A at the third position). The first two positions — GC — still specify alanine. The third-position change is therefore silent: the same tRNA decodes the mutant codon and incorporates the same amino acid. This is why synonymous mutations at the wobble position accumulate faster in evolution and why degeneracy is concentrated at position three.
Question 3 True / False
A single tRNA species with inosine at its anticodon wobble position can decode three different codons that all specify the same amino acid.
TTrue
FFalse
Answer: True
Inosine (I), a modified base common at the wobble position of tRNA anticodons, can form base pairs with U, C, or A in the third codon position. This means one tRNA can decode three synonymous codons — for example, a tRNA reading GCU, GCC, and GCA (all encoding alanine). This is the core mechanism by which the cell needs only ~45 tRNA species to decode 61 sense codons. Without this flexibility, each of the 61 codons would require its own cognate tRNA.
Question 4 True / False
Wobble base pairing allows flexibility at most three positions of the codon-anticodon interaction, which is why the genetic code is degenerate.
TTrue
FFalse
Answer: False
Wobble base pairing is specifically restricted to the third codon position. The first two positions require standard Watson-Crick base pairing (A-U, G-C), which is why changes at positions one or two almost always alter the amino acid specified. Degeneracy is concentrated at the third position precisely because wobble pairing there allows one tRNA to recognize multiple codons. If wobble occurred at all three positions, the specificity needed to translate the correct amino acid would be lost entirely.
Question 5 Short Answer
Explain why the degeneracy of the genetic code is concentrated at the third codon position and how this relates to the number of tRNA species a cell needs.
Think about your answer, then reveal below.
Model answer: The third position of the codon (the wobble position) is geometrically more flexible than the first two — it tolerates non-Watson-Crick base pairs, especially when the tRNA anticodon has modified bases like inosine. This means a single tRNA can recognize multiple codons that differ only at their third base. Because most amino acids that are encoded by multiple codons differ only at position three, the wobble mechanism allows one tRNA to cover all or most of those synonymous codons. The result is that cells need only about 45 tRNA species rather than 61 — one for each sense codon.
Looking at the codon table makes this vivid: glycine is encoded by GGU, GGC, GGA, and GGG — four codons that differ only at position three. A tRNA with inosine at its wobble position handles three of them (GGU, GGC, GGA), and a second tRNA handles GGG. Without wobble pairing, all four would require dedicated tRNAs. This efficiency multiplied across all amino acids explains why biological systems can manage translation with a much smaller set of tRNAs than the codon count would suggest.