The neutral theory of molecular evolution.
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Biomedical subjects
Publications and source records attributed to T H Jukes.
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Codon CUG is used for serine instead of for leucine, its usual assignment, in several yeasts of the genus Candida. We propose a series of steps for the reassignment, including disappearance of leucine CUG and its anticodon CAG, formation of a new serine tRNA, with anticodon CAG, from a duplication of the gene for serine tRNA (IGA), and then production of CUG codons by mutation at sites that are mostly "nonessential."
J.C. Shepherd notes that codons of the type RNY (R = purine, N = any nucleotide base, Y = pyrimidine) predominate over RNR in the genes for proteins. He has hypothesized that RNY codons are the relics of "a primitive code" composed of repeating RNY triplets. He found that RNY codons predominated in fourfold RNN codon sets (family boxes). These family boxes code for valine, threonine, alanine, and glycine. We argue that the proposed "comma-less" code composed of RNY never existed, and that, in any case, survival of such a code would have long since been erased by mutations. The excess of RNY codons in family boxes is probably attributable to preference for the corresponding tRNAs.
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Sequences of several vertebrate mitochondrial tRNAs were aligned and compared. The comparisons were made in pairs of the tRNAs for an identical amino acid. There are 22 genes for different tRNAs in each vertebrate mitochondrial DNA. The closet similarities were between rat and mouse, the next were between mammals, and the widest difference was between human or rat and Xenopus laevis. However, there were very wide variations between different amino acids in each set of comparisons. The time lapse for each percent of difference greatly increased with evolutionary separation. Most of the nucleotide substitutions appeared to be neutral in character.
Schultz and Yarus (J. Mol. Biol. 235:1377-1380, 1994) have proposed that reassignment of codons in the genetic code passes through a stage in which the codons are ambiguously translated. In contrast we state that such ambiguity would be deleterious, and that, to be reassigned, a codon, together with the tRNA that translates the codon, must first disappear from coding sequences, after which a tRNA appears with a mutated anticodon, and this enables the codon to reappear with a changed meaning. In the case of a stop codon, the relevant release factor must change so as to recognize it.
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