Q29. According to the “wobble hypothesis” inosine at the third position of the
anticodon cannot form hydrogen bonds with ________
(A) Adenine
(B) Cytidine
(C) Guanine
(D) Uracil
Inosine in the wobble hypothesis cannot form hydrogen bonds with guanine at the third position of the codon. This is because inosine (I), a deaminated form of adenosine found at the first position (5′ end, or “third” in 3′-5′ anticodon numbering) of many tRNAs, pairs specifically with adenine (A), cytidine (C), and uracil (U) via wobble base pairing, but not guanine (G).
The correct answer is (C) Guanine.
Wobble Hypothesis Overview
The wobble hypothesis, proposed by Francis Crick in 1966, explains the degeneracy of the genetic code by allowing flexible base pairing at the third position of the codon (3′ end) and the first position of the anticodon. Standard Watson-Crick pairing (A-U, G-C) applies to the first two codon positions, but the third position permits non-standard “wobble” pairs, reducing the need for 61 tRNAs to about 40.
Option Analysis
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(A) Adenine: Inosine forms two hydrogen bonds with adenine (I-A pair), a key wobble interaction essential for decoding codons ending in A.
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(B) Cytidine: Inosine pairs with cytidine (I-C pair) via two hydrogen bonds, allowing one tRNA to read codons ending in C.
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(C) Guanine: Inosine does not form stable hydrogen bonds with guanine due to steric and bonding incompatibilities; G requires pairing with C or U, not I.
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(D) Uracil: Inosine pairs effectively with uracil (I-U pair), another classic wobble combination observed in tRNA decoding.
The wobble hypothesis revolutionized our understanding of translation by revealing how inosine at the third position of the anticodon enables flexible codon recognition, but crucially cannot form hydrogen bonds with guanine. This mechanism, vital for CSIR NET Life Sciences aspirants, addresses genetic code degeneracy where one tRNA decodes multiple synonymous codons.
Core Principles of Wobble Hypothesis
Francis Crick’s 1966 wobble hypothesis posits that the third position of the codon (3′ end) pairs loosely with the first position of the anticodon (5′ end, often called the “wobble” or third position in anticodon context). Inosine (I), derived from adenosine deamination, exemplifies this by forming wobble pairs with A, C, or U—but never G—via 1-2 hydrogen bonds, unlike rigid Watson-Crick rules.
Why Inosine Avoids Guanine Pairing
Inosine lacks the full purine structure to stabilize bonds with guanine, which prefers C (three H-bonds) or U (wobble). Structural studies confirm I-G mismatches disrupt ribosomal decoding geometry. This selectivity ensures accurate translation, as I-tRNAs read codons like AUU, AUC, AUA (isoleucine) without G-ending ambiguity.
Biological Significance
Wobble pairing minimizes tRNA needs, enhances efficiency, and buffers mutations at the third codon position. For competitive exams, remember: Inosine anticodon third position hydrogen bonds exclude guanine, distinguishing it from A, C, U pairings.
