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3 The Genomic Tag Hypothesis: What Molecular Fossils Tell Us about the Evolution of tRNA

Nancy Maizels, Alan M. Weiner


Holley’s realization that tRNA could be folded into a two-dimensional cloverleaf posed more questions than it answered (Dudock et al. 1969). One of the most perplexing was whether the three-dimensional structure of tRNA would turn out to be an “integral fold” in which all parts were essential for the correct structure, or whether tRNA could be decomposed into smaller, structurally independent units. The crystal structure of tRNA immediately revealed that tRNA is composed of two perpendicular coaxial stacks (Quigley and Rich 1976): a stack of the acceptor stem on the di-hydrouridine stem/loop (the “top half”) and a stack of the T ψ C stem/loop on the anticodon stem/loop (the “bottom half”) (see Fig. 1). Remarkably, the covalent connections between the middle of one helical stack and the middle of the other hardly distorted either helical stack: The top and bottom halves of tRNA appeared to be inserted into each other with surgical precision. A great deal of evidence has subsequently shown that the top and bottom halves of tRNA are indeed structurally and functionally independent units. This suggests that the two halves of tRNA could have evolved independently. Here we review the experimental evidence bearing on our hypothesis (Weiner and Maizels 1987) that the top half of tRNA evolved first as a 3′ terminal “genomic tag” that marked single-stranded RNA genomes for replication in what Gilbert was first to call the “RNA World” (Gilbert 1986). The bottom half of tRNA would then have evolved separately as replication in the...

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