《Crick 4 *4 *4 遺傳密碼錶》的起草origin與修訂evolution （三）

Three major theories have been suggested to explain the changes in the code. The 『codon capture』 theory (47, 48) proposes that, under mutational pressure to decrease genomic GC-content, some GC-rich codons might disappear from the genome (particularly, a small, e.g., organellar, genome). Then, due to random genetic drift, these codons would reappear and would be reassigned as a result of mutations in non-cognate tRNAs. This mechanism is essentially neutral, i.e., codon reassignment would occur without generation of aberrant or non-functional proteins.

Another concept of code alteration is the 『ambiguous intermediate』 theory which posits that codon reassignment occurs through an intermediate stage where a particular codon is ambiguously decoded by both the cognate tRNA and a mutant tRNA(49, 50). An outcome of such ambiguous decoding and the competition between the two tRNAs could be eventual elimination of the gene coding for the cognate tRNA and takeover of the codon by the mutant tRNA (37, 51). The same mechanism might also apply to reassignment of a stop codon to a sense codon, when a tRNA that recognizes a stop codon arises by mutation and captures the stop codon from the cognate release factor. Under the ambiguous intermediate hypothesis, a significant negative impact on the survival of the organism could be expected but the finding that the CUG codon (normally coding for leucine) in the fungus Candida zeylanoides is decoded as either leucine (3–5%) or serine (95–97%) gave credence to this scenario (37, 52).

Finally, evolutionary modifications of the code have been linked to 『genome streamlining』 (53, 54). Under this hypothesis, the selective pressure to minimize mitochondrial genomes yields reassignments of specific codons, in particular, one of the three stop codons.

The three theories explaining codon reassignment are not exclusive considering that the 『ambiguous intermediate』 stage can be preceded by a significant decrease in the content of GC-rich codons, so that codon reassignment might be driven by a combination of evolutionary mechanisms (55), often under the pressure for genome minimization, especially, in organellar genomes and small genomes of parasitic bacteria such as mycoplasmas (38, 54, 56, 57).

The basic theories of the code nature, origin and evolution

The existence of variant codes and the success of experiments on the incorporation of unnatural amino acids briefly discussed in the preceding section indicates that the genetic code has a degree of evolvability. However, all these deviations involve only a few codons, so in its main features, the structure of the code seems not to have changed through the entire history of life or, more precisely, at least, since the time of the Last Universal Common Ancestor (LUCA) of all modern (cellular) life forms. This universality of the genetic code and the manifest non-randomness of its structure cry for an explanation(s). Of course, Crick』s frozen accident/code expansion theory can be considered a default explanation that does not require any special mechanisms and is only predicated on the existence of a LUCA with a an advanced translation system resembling the modern one (that is, the implicit assumption is that LUCA was not a 「progenote」 with primitive, very inaccurate translation (58)). However, this explanation is often considered unsatisfactory, first, on the most general, epistemological grounds, because it is, in a sense, a non-explanation, and second, because the existence of variant codes and the additional, experimentally revealed flexibility of the code (see above) present a challenge to the frozen-accident view. Indeed, the fact that there seem to be ways to 「sneak in」 changes to the standard code, and yet, the same limited modifications seem to have evolved independently in diverse lineages suggests that the code structure could be non-accidental. Three, not necessarily mutually exclusive main theories have been proposed in attempts to attribute the pattern of amino acid assignments in the standard genetic code to physico-chemical or biological factors or a combination thereof. Rather remarkably, the central ideas of each of these theories have been formulated during the classic age of molecular biology, not long after the code was deciphered or even earlier, and despite numerous subsequent developments, remain relevant to this day. We first briefly outline the three theories in their respective historical contexts and then discuss the current status of each.

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