8 ms·

Floyd does very nice work, but this particular justification -- at least as expressed in this article -- for a 4-base code is completely flawed. The article cla

by lvs 8y ago

Floyd does very nice work, but this particular justification -- at least as expressed in this article -- for a 4-base code is completely flawed. The article claims that the reason to augment the codon table is because only two stop codons could possibly be rewired to code for artificial amino acids. But in fact 43 out of 64 codons could in principle be recoded. That's because of the extraordinary redundancy built into the codon table of 4^3 = 64 codons: there are only 20 coded amino acids, plus one necessary stop codon. So that leaves 43 codons, not 2.

azernik 8y ago
This would require rewriting all the existing DNA, though, to collapse all existing code for those 23 dual-coded amino acids to whichever code we decide is canonical.
- lvs 8y ago
  Not really. It's just a question of codon frequency. Organismic codon bias ensures that some codons are actually used quite rarely in the genome already. Specifically, the frequency of TAG stop codons is ~0.03% in E. coli, and the frequency of TGA is 0.1%. By comparison, the frequency of CTA leucine codons is ~0.3%. So it's only 10-fold more effort than the easiest codon, and ~3X more effort than the next easiest. And it may really not be necessary to recode all of them.
bhk 8y ago
It's not that simple. Even when two codons map to the same amino acid, it doesn't mean they have the same implications. One factor is that different codons translate at different speeds, and these can affect how the protein folds. Another is that base pairs in DNA may have functions or implications apart from their function as part of a codon in a gene. Simply remapping a codon to a new amino acid and re-writing all the genes in a cell's DNA to avoid that codon will cause many things to "break" in a cell's function. Life is a messy, inter-connected system without the clean modularity we like to have in software.
- lvs 8y ago
  "can," "may," ... 1) My argument was simply that the limit on recodable codons is much higher than two, as it was claimed in the article. That's hard to argue with. I didn't say the result in every case would be neutral mutations. 2) The consequences of recoding the stop codons are also not neutral. For example, when Isaacs (eventually) did it, there were severe growth phenotypes in the resulting strain. So I agree that "it's not that simple," which is frankly why I'm not hugely optimistic about this class of endeavors. But the point stands that there is no need in principle for a 4-base code.

by lvs 8y ago

azernik 8y ago

This would require rewriting all the existing DNA, though, to collapse all existing code for those 23 dual-coded amino acids to whichever code we decide is canonical.

lvs 8y ago
Not really. It's just a question of codon frequency. Organismic codon bias ensures that some codons are actually used quite rarely in the genome already. Specifically, the frequency of TAG stop codons is ~0.03% in E. coli, and the frequency of TGA is 0.1%. By comparison, the frequency of CTA leucine codons is ~0.3%. So it's only 10-fold more effort than the easiest codon, and ~3X more effort than the next easiest. And it may really not be necessary to recode all of them.

bhk 8y ago

It's not that simple. Even when two codons map to the same amino acid, it doesn't mean they have the same implications. One factor is that different codons translate at different speeds, and these can affect how the protein folds. Another is that base pairs in DNA may have functions or implications apart from their function as part of a codon in a gene. Simply remapping a codon to a new amino acid and re-writing all the genes in a cell's DNA to avoid that codon will cause many things to "break" in a cell's function. Life is a messy, inter-connected system without the clean modularity we like to have in software.

lvs 8y ago
"can," "may," ... 1) My argument was simply that the limit on recodable codons is much higher than two, as it was claimed in the article. That's hard to argue with. I didn't say the result in every case would be neutral mutations. 2) The consequences of recoding the stop codons are also not neutral. For example, when Isaacs (eventually) did it, there were severe growth phenotypes in the resulting strain. So I agree that "it's not that simple," which is frankly why I'm not hugely optimistic about this class of endeavors. But the point stands that there is no need in principle for a 4-base code.