Buries the caveats a little at the end of the second paragraph: "They have yet to reassemble those pieces into a functioning E. coli."
What they actually did was make copies of the genes in E. Coli, completely remove 7/64 of the codons in those genes, replacing them with synonymous codons, then checked to see that the genes still worked. I imagine they did this by putting them into E. Coli that were missing those genes and seeing if the bacteria could survive using the new gene, but I don't have the full text so I don't know for sure.
In other words if the genome were a book, they replaced all the instances of the letter "y" with "i" and found that the book was still understandable.
It's remarkably hard to do this simple modification, but it's still a ways from completely rewriting a genome. That said, it's a very important first step and hopefully the process of stitching all these things together will be relatively pain free.
The science itself is great, no doubt about that, but calling this a "radically rewritten bacterial genome" is over the top. And I get the impression they have a long way to go yet...
Thanks for that - I suppose, I would only say that your analogy might be tweaked a bit. It wasn't so much that they replaced y with i as "however" with but.
This paper is cool because they've optimized the E. coli genome to entirely eliminate certain codons, which would, for example, prohibit infection by viruses that depend on particular codons. It also frees up codons for other usage, including novel tRNA complexes. The paper mentions the authors have validated 55 recoded segments of 50kb each. At ~$0.10/bp that would cost $577,500 for the DNA alone, though the authors likely paid less or synthesized the fragments in-house.
This is somewhat related to codon optimization, which is typically employed when genes are added to an organism to enhance expression, since codon usage bias[1] varies by host organism. If you modify an inserted gene so its codons match the dominant synonymous tRNA present, you'll see higher expression of the gene product. If you're engineering E. coli to produce insulin, your bioreactor will produce more of it for a given amount of feedstock.
I've always thought the redundant encoding allowed for variations in stability. Some encodings of a protein can be subjected to more mutations than others without affecting the resulting protein. The different variations may (I haven't looked) allow a higher number of "neighbor" proteins that can be reached through a single mutation if we consider a codon variation not to be a mutation if the resulting protein is identical. These are things that may have effects on evolution, but not the individual.
> They were able to reduce the number of codons by synthesizing the DNA in 55 fragments, each of which was 50,000 base pairs long. They have yet to reassemble those pieces into a functioning E. coli.
> We have validated 63% of recoded genes by individually testing 55 segments of 50 kilobases each. We observed that 91% of tested essential genes retained functionality with limited fitness effect.
It's because I've seen your comments before and you have a consistent pattern of curtly disagreeing without adding to the conversation. It's frustrating and I want HN to be better.
Yes, they tested each piece, probably in 55 different variants of E. Coli. The gene has been converted to RNA and then to protein. That counts as "the code has been executed" in my analogy. If you're gonna be a pill at least do some further reading.
Ok I'll try. You are right I misread that - I didn't think 'tested' meant in-situ, and that plus the later statement about not trying it complete was where I was coming from.
Its just that curtness in writing is in the eye of the beholder. I strive for a concise style. That clearly isn't taken well by everybody.
What they actually did was make copies of the genes in E. Coli, completely remove 7/64 of the codons in those genes, replacing them with synonymous codons, then checked to see that the genes still worked. I imagine they did this by putting them into E. Coli that were missing those genes and seeing if the bacteria could survive using the new gene, but I don't have the full text so I don't know for sure.
In other words if the genome were a book, they replaced all the instances of the letter "y" with "i" and found that the book was still understandable.
It's remarkably hard to do this simple modification, but it's still a ways from completely rewriting a genome. That said, it's a very important first step and hopefully the process of stitching all these things together will be relatively pain free.