
‘Radically rewritten’ bacterial genome unveiled - okket
http://www.nature.com/news/radically-rewritten-bacterial-genome-unveiled-1.20451
======
entee
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.

~~~
veddox
Yes, definitely a hyped up story.

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...

------
tomkinstinch
Full PDF:
[http://science.sciencemag.org/content/sci/353/6301/819.full....](http://science.sciencemag.org/content/sci/353/6301/819.full.pdf)

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](https://en.wikipedia.org/wiki/Codon_usage_bias)

~~~
phkahler
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.

------
mmastrac
> 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.

So it compiles, but it doesn't run.

~~~
civilian
I think in this analogy, it compiles & runs & passes it's unit tests, but it
hasn't been deployed or had integration tests run on it.

~~~
JoeAltmaier
Its never been executed at all.

~~~
civilian
_> 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._

Yes it has.
[http://science.sciencemag.org/content/353/6301/819](http://science.sciencemag.org/content/353/6301/819)
And you sound like a jerk when you reply in the negative with no proof.

~~~
JoeAltmaier
"They have yet to reassemble those pieces into a functioning E. coli."

Sure sounds like they haven't tested them yet. Maybe unit-tested the
individual changes in a test tube?

Speaking of character, I wonder what kind of person throws in random off-topic
aspersions ?

~~~
civilian
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.

~~~
JoeAltmaier
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.

