‘Radically rewritten’ bacterial genome unveiled

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.

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.

1. https://en.wikipedia.org/wiki/Codon_usage_bias

So it compiles, but it doesn't run.