> That said, they edits were deliberately just replacing like with like, so it would be expected that they survive.
To the extent that we only consider encoded proteins, sure. But DNA and RNA has secondary and tertiary structure that does things - it isn't just bits on a hard drive. Riboswitches and Catalytic RNA are good examples.
> the elevated temperature inside the host's body melts the secondary structure of a segment in the 5' untranslated region of the mRNA produced by the bacterial prfA gene. As a result of this alteration in secondary structure, a ribosome-binding site is exposed, and translation of protein can take place
> as long as it wasn't directly fatal the bacteria would grow
The abstract states that 18,214 occurrences were edited. The fact that such drastic structural changes to DNA and RNA weren't immediately fatal is what surprises me. It's believable enough, but I would not have predicted it.
I wonder if they just got lucky with (or perhaps strategically chose) the specific codon substitutions to perform? Would a different set of synonym substitutions have been nonviable?
> I'd be interested in seeing how much change was accumulated after 24 hours.
Very much this. Also, a sibling comment mentions the E. coli long-term evolution experiment; I'd be very interested to find out what changed to compensate for this over hundreds or even thousands of generations.
> I wonder if they just got lucky with (or perhaps strategically chose) the specific codon substitutions to perform? Would a different set of synonym substitutions have been nonviable?
Recoding scheme was strategically chosen. They cite 2016 paper (PMC5035903) which showed substituting AGA with CGA (synonymous codon for arginine) on E. coli was nonviable.
> Successful replacement codons tended to conserve local ribosomal binding site-like motifs and local mRNA secondary structure, sometimes at the expense of amino acid identity. Based on these observations, we empirically defined metrics for a multidimensional “safe replacement zone” (SRZ) within which alternative codons are more likely to be viable.
Why is it surprising that it isn't fatal? They picked relatively rare codons, and they slotted the changes in sequentially. The process of inserting dna is selective (plating lawns of bacteria and picking colonies), probably the fastest growing colonies had the opportunity to build in compensatory mutations if there were subtle secondary or tertiary XNA features that were mildly deleterious.
To the extent that we only consider encoded proteins, sure. But DNA and RNA has secondary and tertiary structure that does things - it isn't just bits on a hard drive. Riboswitches and Catalytic RNA are good examples.
For example: (https://www.nature.com/scitable/topicpage/rna-functions-352)
> the elevated temperature inside the host's body melts the secondary structure of a segment in the 5' untranslated region of the mRNA produced by the bacterial prfA gene. As a result of this alteration in secondary structure, a ribosome-binding site is exposed, and translation of protein can take place
Riboswitch overview: (https://www.nature.com/scitable/topicpage/riboswitches-a-com...)
> as long as it wasn't directly fatal the bacteria would grow
The abstract states that 18,214 occurrences were edited. The fact that such drastic structural changes to DNA and RNA weren't immediately fatal is what surprises me. It's believable enough, but I would not have predicted it.
I wonder if they just got lucky with (or perhaps strategically chose) the specific codon substitutions to perform? Would a different set of synonym substitutions have been nonviable?
> I'd be interested in seeing how much change was accumulated after 24 hours.
Very much this. Also, a sibling comment mentions the E. coli long-term evolution experiment; I'd be very interested to find out what changed to compensate for this over hundreds or even thousands of generations.