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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

#11

Post by chubot »

maxerickson wrote: post #8
daemonk wrote: 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…

If I understand correctly, they built the technology to synthesize arbitrary genomes. So they remove genes by omitting them from the synthesis.

The article says they tried the additive/synthesis approach first, which didn't work. And then they tried the subtractive approach, starting with M. Mycoides. And in that case they were left with a lot of "unexplained" genes.

But he reminds us that the subtractive process entirely depends on the starting cell.

I would like to hear more about the difference between additive and subtractive methods -- it wasn't entirely clear from the article.

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

#12

Post by maxerickson »

chubot wrote: post #11
maxerickson wrote: post #8

Earlier quoted context omitted.

If I understand correctly, they built the technology to synthesize arbitrary genomes. So they remove genes by omitting them from the synthesis.

The article says they tried the additive/synthesis approach first, which didn't work. And then they tried the subtractive approach, starting with M. Mycoides. And in that case they were left with a lot of "unexplained" genes. But he reminds us that the subtractive process entirely depends on the starting cell. I would like to hear more about the difference between additive and subtractive methods -- it wasn't entirel…

Yes, for the design of the genome.

As far as I can tell, they synthesized the molecule.

A line from the paper...:

We used whole-genome design and complete chemical synthesis to minimize

I did fret for a second over what meaning of "remove" daemonk was using (from the design? From the instantiation of the genome?) but decided I at least wasn't posting misinformation.

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

#13

Post by daveguy »

sevenless wrote: post #4

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 the scientific community to accept epigenetics as a valid influence and avenue of study (due to both a lack of methods to accurately study these aspects of an organism and scientific inertia).

edit: pedantics.

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

#14

Post by Retric »

davnn wrote: 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.

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

#15

Post by grey413 »

sevenless wrote: post #4

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.

That's actually already an area of active study.

See http://www.sciencedirect.com/science/article/pii/S1534580708...

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

#16

Post by smaili »

sixQuarks wrote: post #7

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?

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

#17

Post by daveguy »

davnn wrote: 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…

> They found that not a single gene is shared across all of life.

It is definitely a function vs identity. Many mutations of a single gene can perform the same function -- there is a lot of redundancy in genetic code.

>If he had done the same set of experiments with a different microbe, he points out, he would have ended up with a different set of genes.

This is very interesting. I expect also, that if they proceeded with their knockout in a different order or different sets at one time they would end up with a different set of genes. Maybe they have some massively parallel way to knockout genes, but I doubt they have explored the entire set of knockouts from the original functioning natural organism. They very likely could be at a local minima of genes required (eg no single gene can be knocked out, but no where near the absolute minimum).

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

#18

Post by searine »

davnn wrote: 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…

>As @sixQuarks has already written, finding the minimal amount of genes when there are 175 unknown...seems to be pretty much impossible.

The point isn't the minimal genome, it's to identify the genes important for a minimal genome.

Genetics is all about filtering the signal from the noise. Now we know that these 175 genes are important, we can start focusing efforts on them.

The problem isn't that we don't know how to figure out what a gene does, it's that there are so many goddamn genes we don't know where to start.

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

#20

Post by 0xfeba »

davnn wrote: 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 deeply believed that organisms share the same basic set of genes.

Many groups of organisms do. All organisms is a tall order, if you think about it.

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