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According to the wobble rules, which base of the codon can be mismatched with an anticodon base on the tRNA?

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Final answer:

The third base of the codon can 'wobble' and pair with a tRNA anticodon base that does not necessarily match perfectly according to standard base pairing rules, allowing flexibility in the recognition of codons by tRNAs.

Step-by-step explanation:

According to the wobble hypothesis, which was introduced by Francis Crick in 1966, the base of the codon that can be mismatched with an anticodon base on the tRNA is the third base. The first two bases of the codon pair strictly according to the standard base pairing rules, while the third base can 'wobble' or base pair more flexibly. This wobbling allows for codons that differ in their third nucleotide to be recognized by the same tRNA. For example, inosine (I) in the first position of the anticodon can base pair with U, C, and A in the third position of the codon.

Further, certain modifications to the first base of the anticodon can change its pairing properties. An example of this is a tRNA with the anticodon containing inosinate (I), which can base pair with three different nucleotides: U, C, and A. This flexibility in the wobble position allows a single tRNA to recognize codons of the same amino acid that differ at the third nucleotide position. This phenomenon is essential in the economy of the cell's use of tRNA species and contributes to the robustness of the protein translation process.

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