5 ms·

I don't think that's entirely correct. > The bacteria are alive, though unusually shaped and reproducing slowly. If I understand correctly, they completely re

by Reelin 7y ago

I don't think that's entirely correct. > 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.

dnautics 7y ago
It's e coli. Theyre like weeds, plus we coddle them in the lab.
olliej 7y ago
E. Coli is super robust even in adverse conditions, and a lot of the coding regions are essentially to support those adverse conditions. 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.
- Reelin 7y ago
  > 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. For example: (https://www.nature.com/scitable/topicpage/rna-functions-352 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-common-rna-regulatory-element-14262702 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.
  - sanxiyn 7y ago
    > 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.
    - Reelin 7y ago
      That is a really neat paper. > 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.
  - dnautics 7y ago
    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.
quotemstr 7y ago
> Given how important tertiary DNA and RNA structure is, I think it's remarkable that they're alive at all. 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_experiment https://en.wikipedia.org/wiki/E._coli_long-term_evolution_ex...

by Reelin 7y ago

dnautics 7y ago

It's e coli. Theyre like weeds, plus we coddle them in the lab.

olliej 7y ago

E. Coli is super robust even in adverse conditions, and a lot of the coding regions are essentially to support those adverse conditions. 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.

Reelin 7y ago
> 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. For example: (https://www.nature.com/scitable/topicpage/rna-functions-352 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-common-rna-regulatory-element-14262702 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.
- sanxiyn 7y ago
  > 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.
  - Reelin 7y ago
    That is a really neat paper. > 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.
- dnautics 7y ago
  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.

quotemstr 7y ago

> Given how important tertiary DNA and RNA structure is, I think it's remarkable that they're alive at all. 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_experiment https://en.wikipedia.org/wiki/E._coli_long-term_evolution_ex...