Well, one thing they've proved by doing that is that the redundant codings didn't do anything unexpectedly important.
> The bacteria are alive, though unusually shaped and reproducing slowly.
If I understand correctly, they completely removed two serine encodings and one stop codon encoding. Given how important tertiary DNA and RNA structure is, I think it's remarkable that they're alive at all.
Lab conditions are super friendly to E. coli - they're plated on agar that is tailored to them, kept at a temperature that is tailored to them, and the plates are sterilized so that they have no competitors.
So even if the initial cells were super unhealthy, as long as it wasn't directly fatal the bacteria would grow, and bacteria evolves quickly - fast enough that I'd be interested in seeing how much change was accumulated after 24 hours.
That said, they edits were deliberately just replacing like with like, so it would be expected that they survive.
Interesting follow on research: If you repeatedly ensured that they dropped the alternate serine codings, could you convince it to treat the alternate codings as being something other than serine: the careful engineering would have removed the selective pressure on those codings being serine.
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.
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.
It'd be interesting to add these things to the famous E. coli long-term evolution experiment [1] and see how many of the removed codons reappear due to beneficial spontaneous mutations that revert Dr. Chin's changes.
[1] https://en.wikipedia.org/wiki/E._coli_long-term_evolution_ex...