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In Newly Created Life-Form, a Major Mystery

quantamagazine.org

41–50 of 144 posts

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

#41
This is great. This is the proper engineering approach to understanding life. Whittle it down to the minimal reproducing test-case, and poke it with a stick until you understand what all the parts do.

This is just excellent science. It seems like it should be very easy to get these unknown genes to reveal their function now. Very exciting times.

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

#42
Interesting work, but it reminds me of the famous "Could a biologist fix a radio?" paper [1]. The paper imagines biologists trying to determine what parts of a radio are essential using a similar trial and error technique. As you can imagine, this technique would lead to many erroneous conclusions, especially when paired with the "publish or perish" and "gold rush" mentalities so prevalent in academia. It makes you wonder if we are trying to understand biological systems with a fundamentally wrong approach.

[1] https://www.cmu.edu/biolphys/deserno/pdf/can_a_biologist_fix...

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

#43
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.

Shouldn't they have replaced them with a gene of the same length, filled with only stop codons?

Otherwise, it would be like cutting out instructions from an assembly language file, without knowing whether one of the instructions does something like adding a constant integer value to the program counter. You might think the code that was removed was critical to the operation of the program, but you could have instead replaced all the instructions with an equivalent number of no-ops, and it would still work as expected.

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

#44
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…

>In fact, there’s no single set of genes that all living things need in order to exist. ... They found that not a single gene is shared across all of life.

Isn't the current theory that all life on Earth has a common ancestor? Wouldn't this point put that into question and introduce the possibility that life has developed multiple times independently of each other or would this lack of shared genes eventually appear through divergent evolution? It seems like the former option would greatly increase the fl component in the Drake Equation meaning alien life is even more likely than previously thought.

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

#45
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?

When you're talking about 175 different genes, there are far more combinations of genes than there are atoms in the universe.

Perhaps a quantum computer can tackle this kind of problem, but nothing we have today can brute-force the solution.

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

#46
post #17
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…

Years ago I read an interesting paper comparing the types of subsystems found in the Linux kernel with subsystems found in biology (or what we understand of them currently).

There is a lot of redundancy in biology, which allows for biological systems to be pretty robust, adaptable and fault tolerant. Of course this also means it's really hard to fix that biological process when things go horribly wrong, such as in many forms of cancer.

Paper: “Comparing genomes to computer operating systems in terms of the topology and evolution of their regulatory control networks.” By Koon-Kiu Yan, Gang Fang, Nitin Bhardwaj, Roger Alexander, Mark Gerstein. Proceedings of the National Academy of Sciences, Vol. 107 No. 18, May 4, 2010.

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

#47
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?

They got it down to 473 genes, but let's say that minimal life is some 20 of those genes. A brute force approach would require trying 10^34 combinations[1]. And that's already with the simplifying assumption that 20 genes is the minimal set rather than 19 or 106 or some other subset.

[1] http://www.wolframalpha.com/input/?i=473+choose+20

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

#48

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.

Actually there are new approaches to study exactly that, and they are developing rapidly, cf: https://en.wikipedia.org/wiki/Chromosome_conformation_captur... Basically, this problem, along with a long list of other applications is being attacked by deep sequencing. The way it works is that you apply a treatment to DNA that 'glues' 3D contacts in place and covers the glued segment, apply restriction enzymes to cut out what's not covered by glue, get rid of the glue, sequence all that's left, and then map the remaining sequenced fragments to the reference genome. The output is the relative tendency of different regions to come into contact with each other.

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

#49

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.

Shouldn't they have replaced them with a gene of the same length, filled with only stop codons? Otherwise, it would be like cutting out instructions from an assembly language file, without knowing whether one of the instructions does something like adding a constant integer value to the program counter. You might think the code that was removed was critical to the operation of the program, but you could have instead…

Stop codons aren't a noop either though, since genes can encode different functionality based on "intentional" frameshifts by various means.

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

#50
post #44
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…

>In fact, there’s no single set of genes that all living things need in order to exist. ... They found that not a single gene is shared across all of life. Isn't the current theory that all life on Earth has a common ancestor? Wouldn't this point put that into question and introduce the possibility that life has developed multiple times independently of each other or would this lack of shared genes eventually appear…

I would guess that the earliest life didn't accidentally hit upon optimal or even reasonably good ways to do whatever is needed to reproduce.

If that's the case, it isn't that unlikely that every evolutionary branch managed to improve (or discard) every part of the original machinery in some way.

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