"A speculation on the origin of protein synthesis"

Date:: 1976

Reference:: PP/CRI/I/1/30

Credit: "A speculation on the origin of protein synthesis". Source: Wellcome Collection.

7/10

$If we are prepared to relax the rule that there must always be five good base pairs in both the FH and the hf configurations then we can use for the anticodon loops the family 3' \JGNYR(U)U which corresponds to the set of codons at the cost of occasional U = C and U = U pairs (which may be possible but rather weak (Crick, 1966)) in the position marked with a bracket. In the present code this adds the amino acids tyrosine, cysteine, histidine and arginine. A less likely alternative is the family 3' C U)GYNRUU which corresponds to the codon set . The additional amino acids for these codons are at present isoleucine, threonine, valine and alanine. Both of these codon sets, separately, are comma-free. The second set is less attractive in that the possible weaker base pairing occurs not only in the hf configuration but also in the FH con figuration. This latter is the configuration needed to hold the growing polypeptide chain to the mRNA and one might expect it to be the most stable of all. Note however that these codons might have included GC^ which now codes for alanine, another likely candidate for a primitive amino acid and that, since three G = C base pairs would give extra stability, the use of the codon GCC, combined with the four mentioned previously, is not unattractive. Whatever the details, the point is that new anticodons can be introduced by relaxation of the original rules. 7. A Difficulty There is one possible difficulty with the type of scheme outlined above which should not be overlooked. The comma-free conditions largely prevents a tRNA going on in the wrong phase; that is, displaced by 1, 2, 4, 5, ... bases, but a tRNA can quite happily bind with 5 base-pairs displaced by 3 bases from the proper position. If it persisted there indefinitely, and if the nascent polypeptide chains could not be trans ferred to the amino acid of this tRNA then further synthesis would be blocked. This difficulty is not so great if there is a weak nonspecific affinity, as we have assumed, between two adjacent tRNAs, but not between two tRNAs spaced one or more bases apart on the mRNA. Indeed it would be better if a single tRNA in the hf configuration did not bind too strongly so that it could float away from the mRNA after a moderately short time. If this were so polypeptide synthesis would only be delayed rather than stopped completely should it have gone on in the wrong place. The additional binding of the entering tRNA, with its amino acid, when in the correct position next to the previous tRNA (having the nascent chain attached) would help stabilise this important complex. In the latter stages of the evolution of the code a primitive ribosome might make it unnecessary for a tRNA to interact with more than three base pairs and all comma-free constraints would then be removed. At the same time modification of the anticodon loop might remove unwanted pairing outside the anticodon triplet itself, as is found in many tRNAs today. Once the comma-free restraints were removed$

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"A speculation on the origin of protein synthesis"

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