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In Newly Created Life-Form, a Major Mystery

quantamagazine.org

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Re: In Newly Created Life-Form, a Major Mystery

#31
post #14
post #10

TL;DR: Venter and his collaborators originally set out to design a stripped-down genome based on what scientists knew about biology. ... With the right tools finally in hand, the researchers designed a set of genetic blueprints for their minimal cell and then tried to build them. Yet “not one design worked," ... So the team took a different and more labor-intensive tack, replacing the design approach with trial and e…

Not all life has DNA.

[deleted]

Re: In Newly Created Life-Form, a Major Mystery

#32
post #29
post #22

Earlier quoted context omitted.

Do you know an article about that? Did not find anything about a life form without DNA, except http://news.nationalgeographic.com/news/2010/12/101202-nasa-... . The definition of life itself is not really obvious to me either, some sources count viruses as life other don't.

The definition of life is a tricky question. The most obvious example is red blood cells dump their DNA. So they can't replicate, and virus can't target them. However, insect drones also can't reproduce and are considered alive so it's a little more open to debate than you might think. As to life without DNA. The methodology is somewhat in question for this but here is a more in depth link: http://science.sciencemag.…

The paper you cite about the bacterium that uses arsenic instead of phosphorus in its DNA was conclusively discredited. http://www.nature.com/news/arsenic-life-bacterium-prefers-ph...

Re: In Newly Created Life-Form, a Major Mystery

#33
post #10

TL;DR: Venter and his collaborators originally set out to design a stripped-down genome based on what scientists knew about biology. ... With the right tools finally in hand, the researchers designed a set of genetic blueprints for their minimal cell and then tried to build them. Yet “not one design worked," ... So the team took a different and more labor-intensive tack, replacing the design approach with trial and e…

My understanding is that all known organisms share at least the ribosome RNA genes. Unless you're counting viruses, which is not exactly fair since they hijack the host's ribosomes.

Re: In Newly Created Life-Form, a Major Mystery

#34
post #13

I find it fascinating we still don't really know how life works. I have a hunch we are going to find the large scale 3D structure of the chromosome is a big deal, and these genes regulate it. There aren't many good tools to study chromosome structure and it's quite possible there's a whole layer of information we've missed so far.

There is a significant branch of microbiology that studies the 3D structure of chromosomes. Epigenetics is the study of how gene expression (rather than composition) affects a phenotype. There is a strong influence of structure, telomeres, centromeres, and expression modifiers that work at a physical level. It will certainly be a major component of functional life. It took decades after genetics were established for…

that's not biochemistry- it's structural biology. Biochemistry focuses almost entirely on reducible components in isolation.

Re: In Newly Created Life-Form, a Major Mystery

#35
post #10

TL;DR: Venter and his collaborators originally set out to design a stripped-down genome based on what scientists knew about biology. ... With the right tools finally in hand, the researchers designed a set of genetic blueprints for their minimal cell and then tried to build them. Yet “not one design worked," ... So the team took a different and more labor-intensive tack, replacing the design approach with trial and e…

I worked in the synthetic biology lab (on a different project) while the early stages of the Syn3.0 was being done, and also have paid several visits to chat with them in the meantime. [Proof: first author on http://dx.doi.org/10.3390/ijms16012020] I was a fly on the wall for most of the group meetings and even contributed some unpublished results (there were transposons that were causing problems by shuffling the the DNA in the yeast and I hypothesized the orientation that causes the issue and discovered the yeast genes responsible for this process)

Firstly what constitutes "minimal" depends on what you feed the organism. There's a set of bacteria called phytoplasma which are plant parasites that are missing genes to make nucleotides (even mycoplasmas have those) and they've adapted by sucking nucleotides from their hosts.

Some insider information: Most of the mystery essential genes are vague cell wall proteins. Probably what is going on is that if you knock out too many of these genes, you lose cell wall turgidity and the cell becomes nonviable. So what is important is not so much which of these genes you have, but how many of them you have.

Second insider information, for fun: The "hypothetical minimal genome" (syn2.0 is referred to as HMG in the paper) was actually a backronym because we called it the "hail mary genome" but decided that was inappropriate for publication.

Re: In Newly Created Life-Form, a Major Mystery

#36
That's like forking someone's program, but not understanding two thirds of the code. (What's the big deal? It happens!)

If you take someone's 4000-5000 line program and whittle it down to 473 lines which are still somehow useful, "newly created" doesn't apply in full honesty, let alone if you don't know what a third of those lines do.

Re: In Newly Created Life-Form, a Major Mystery

#37
post #10

TL;DR: Venter and his collaborators originally set out to design a stripped-down genome based on what scientists knew about biology. ... With the right tools finally in hand, the researchers designed a set of genetic blueprints for their minimal cell and then tried to build them. Yet “not one design worked," ... So the team took a different and more labor-intensive tack, replacing the design approach with trial and e…

I worked in the synthetic biology lab (on a different project) while the early stages of the Syn3.0 was being done, and also have paid several visits to chat with them in the meantime. [Proof: first author on http://dx.doi.org/10.3390/ijms16012020 ] I was a fly on the wall for most of the group meetings and even contributed some unpublished results (there were transposons that were causing problems by shuffling the t…

> So what is important is not so much which of these genes you have, but how many of them you have.

That hints that you could just duplicate the same cell wall protein gene instead, right?

Re: In Newly Created Life-Form, a Major Mystery

#38
post #16

I'm afraid it's not the individual genes themselves that are important to life, but a specific combination of those genes. Further complicating the problem is that we have no idea how many genes comprise an "essential group". Is it a combination of 2 genes? 3, 5, 10? When you're talking about 175 unknown genes, the combination of all of these is a huge number. It's like finding a needle in a haystack the size of the…

> I don't think this brute force approach is going to work, we need a different way to figure this out, but I'm confident that once figured out, it will seem simple looking back on it. Why not? Couldn't we use machines to automate this and analyze the results?

I think it might take a while.

http://coolconversion.com/math/factorial/What-is-the-number-...

Re: In Newly Created Life-Form, a Major Mystery

#39
post #3

I wonder how they removed the genes? I am not an expert in microbiology. I work with mainly eukaryotes, but I am guessing intergenic distances are not a huge factor here? What about spatial arrangement of the genes? Did they generally leave that alone? Genes are not independent functional modules. Their placement and arrangement on the genome matters. Did they only mess with coding features (genes)? Or did they also…

with a handful of exceptions (for example TER units, and DnaA, which seems to need to be close to the replication origin), for most microbes, placement and arrangement don't matter.

I believe they wanted to modularize the bacteria by placing cassettes of common functionality (e.g. all the tRNAs together) in parts of the genome. I don't know if they are still are working on that, or how it went.

In yeasts, the tRNAs have to be in the same orientation as the replication bubble, but there didn't seem to be that restriction in mycoplasmas.

Re: In Newly Created Life-Form, a Major Mystery

#40

Earlier quoted context omitted.

I worked in the synthetic biology lab (on a different project) while the early stages of the Syn3.0 was being done, and also have paid several visits to chat with them in the meantime. [Proof: first author on http://dx.doi.org/10.3390/ijms16012020 ] I was a fly on the wall for most of the group meetings and even contributed some unpublished results (there were transposons that were causing problems by shuffling the t…

> So what is important is not so much which of these genes you have, but how many of them you have. That hints that you could just duplicate the same cell wall protein gene instead, right?

presumably. Or just put in fewer of them, behind stronger promoters.
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