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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 fi
by davnn 10y ago
TL;DR: Venter and his collaborators originally set out to design a stripped-down genome based on what scientists knew about biology.
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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,"
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So the team took a different and more labor-intensive tack, replacing the design approach with trial and error. They disrupted M. mycoides’ genes, determining which were essential for the bacteria to survive.
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Venter is careful to avoid calling syn3.0 a universal minimal cell. 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.
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In fact, there’s no single set of genes that all living things need in order to exist.
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They found that not a single gene is shared across all of life. “There are different ways to have a core set of instructions,”
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Venter’s minimal cell is a product not just of its environment, but of the entirety of the history of life on Earth.
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He and others are trying to make more basic life-forms that are representative of these earlier stages of evolution.
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Some scientists say that this type of bottom-up approach is necessary in order to truly understand life’s essence. “If we are ever to understand even the simplest living organism, we have to be able to design and synthesize one from scratch,”
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“We are still far from this goal.”
As @sixQuarks has already written, finding the minimal amount of genes when there are 175 unknown ones and you don't know anything about their dependencies and relationships seems to be pretty much impossible.
> 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.
That's the most interesting point to me, I deeply believed that organisms share the same basic set of genes.
- Retric 10y agoNot all life has DNA.
- davnn 10y agoDo 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-announcement-arsenic-life-mono-lake-science-space/ 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.
- Lyaserkiev 10y agoI'm guessing he means RNA viruses https://en.m.wikipedia.org/wiki/RNA_virus https://en.m.wikipedia.org/wiki/RNA_virus
- Retric 10y agoThe 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.org/content/332/6034/1163.full http://science.sciencemag.org/content/332/6034/1163.full Now, this is really 1:1 with DNA just using slightly different chemistry, but it's hard to call something DNA when you swap out one of the building blocks. Other examples are hard to locate in large part because you can't direct detect this stuff. Anyway, my point was while a virus is 'stuck' using DNA as it needs to infect things that use DNA. However, they can use RNA internally. PS: For a really out there example, prions seem really close to life.
- kens 10y agoThe 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-phosphorus-after-all-1.11520 http://www.nature.com/news/arsenic-life-bacterium-prefers-ph...
- Retric 10y agoThis does not mean that arsenate does not get into the bacteria, he points out. “It just shows that this bacterium has evolved to extract phosphate under almost all circumstances.” Yes, it really wants phosphorus. But, a strong preference does not create phosphorus when there is none to be found. Not that single cells really want or try etc, but you get the idea.
- derekp7 10y agoOne definition that I like to include in defining life, is something that uses energy to decrease (or maintain?) local entropy.
- deleted 10y ago[deleted]
- julienchastang 10y agoThis comment is not as absurd as everyone seems to think. It is possible that life started out as RNA[1] on Earth or elsewhere in the galaxy[2]. [1] https://en.wikipedia.org/wiki/RNA_world https://en.wikipedia.org/wiki/RNA_world [2] https://en.wikipedia.org/wiki/Panspermia https://en.wikipedia.org/wiki/Panspermia
- dekhn 10y agoI'm not aware of any life which lacks DNA. This is kind of "definitional" - really depends on your definition of life, but I don't include viruses, because they don't have a regulated metabolism.
- daveguy 10y ago> 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).
- djsumdog 10y agoYears 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.
- majkinetor 10y agoThanks for that last paper, epic! Perhaps a good moment to refer to this one: Cancer tumors as Metazoa 1.0: tapping genes of ancient ancestors http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3148211/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3148211/
- majkinetor 10y agoThis means that we need first to decide on common environment that minimal synthetics will live on. Then, with this environment fixed, we could try to isolate minimal set of genes for multiple different organisms that are originally viable in this environment. Such environment should also be 'minimal' - i.e. having lowest number of resources required to construct it and lowest amounts of those resouces.
- searine 10y ago>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.
- 0xfeba 10y ago> 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.
- jhoechtl 10y agoThe more I think about that the more makes me believe that the Genome is not the smallest order which defines "life". Maybe all is hidden behind getting blurry because of Heisebergs uncertainty principle.
- alextheparrot 10y agoIf you consider the genome to be information, life is effectively the process that information supports by encoding a method to accomplish the process. Replicating and using energy in a coordinated manner are two processes of life, but their information-based encoding can differ significantly based on the method used.
- Florin_Andrei 10y agoIt's the process of making things work in a cell. Turns out, there are more than one encoding for how to make that happen.
- rcthompson 10y agoMy 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.
- cowsandmilk 10y agobut there is RPL1 up to RPL41, and same for RPS and then MRPL and MRPS , so despite the similarities, one can argue different organisms may have different rRNA genes.
- rcthompson 10y agoRPL1 and such are genes for ribosomal proteins. I'm talking about the genes that encode the ribosomal RNA subunits. These genes are used to infer the evolutionary relationships of the tree of life, so presumably they are shared across all known organisms, or else it would not be possible to infer a phylogenetic tree.
- dnautics 10y agoI 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 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.
- golergka 10y ago> 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?
- dnautics 10y agopresumably. Or just put in fewer of them, behind stronger promoters.
- stcredzero 10y agoThe "hypothetical minimal genome"...was actually a backronym because we called it the "hail mary genome" but decided that was inappropriate for publication. One in-house ORM I worked with was called TFP, because it was entirely written on a plane ride to Houston, and they named it TFP because the authors liked to say they wouldn't touch it again with a ten foot pole. Their company later thought about trying to sell it, with the name "Technique for Persistence."
- slg 10y ago>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.
- Someone 10y agoI 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.
- deleted 10y ago[deleted]
- Zigurd 10y agoOnly if all life converges on having dna. If there are multiple origins of life that survive there would probably be multiple different self replicating molecules.
- gort 10y ago"Isn't the current theory that all life on Earth has a common ancestor? Wouldn't this point put that into question" Not really. For one thing there's too much commonality across life in terms of things like the genetic code, i.e. what a sequence of genetic letters "means". The genetic code is arbitrary but essentially universal with minor variants. For another thing, the organisms now present can be separated from each other by as much as 8 billion years of evolution (4 billion on each branch) meaning there's no particular reason to expect some shared gene to be present everywhere. New genes arise as mutations from old ones, old genes become obsolete and get removed, etc. It's vaguely like how, if you fork a coding project, and the two projects are allowed to continue indefinitely, eventually there might be no code in common, even without a complete rewrite ever happening.
- stcredzero 10y agoIs there a single set of instructions needed for Turing Completeness? It's possible to have Turing Completeness in a random access machine with just one instruction. I should think you really need to satisfy certain capabilities, and there would be many ways to satisfy those.
- nickpsecurity 10y agohttps://news.ycombinator.com/item?id=9751312 https://news.ycombinator.com/item?id=9751312
- thaumasiotes 10y ago> I deeply believed that organisms share the same basic set of genes They do. What you're responding to says there's no one gene shared by all organisms. The genetic intersection of any two organisms is large; the genetic intersection over all organisms is empty.
- gr3yh47 10y ago>That's the most interesting point to me, I deeply believed that organisms share the same basic set of genes. this seems to support the idea that instead of evolving from a single ancestral life form, all beings were created with care edit: or at least would seem to support the weaker assertion that singl life form ancestry evolutionary theory is inaccurate. if this is logically incorrect please feel free to tell my why. downvotes are not for disagreement!
- pluma 10y agoIt's obviously incorrect. It's not even really a logic error, it's a category error. At face value the statement "if not all living things share a common ancestor, that makes them appear more like they were intentionally created" (although that line of reasoning, i.e. the watchmaker argument, has been debunked time and time again) seems reasonable. However the statement seems far more grandiose than it actually is. If two very "primitive" organisms (i.e. operating at a much lower complexity with much smaller and fewer moving parts than even, say, an earthworm) don't share their sets of DNA that may be unexpected (because whatever step there was from "not having DNA" to "having DNA" had to happen twice, separately, successfully). If we found out that, say, all higher lifeforms shared no common DNA with other lifeforms outside their group and those groups closely aligned to the Christian "kinds" (which don't really map to biologically distinct groups in meaningful or consistent ways) THAT would be astounding. But even that extreme case wouldn't make the "creation hypothesis" (if you even want to call it that) more plausible because it presumes the existence of an unexplained organism that is far more complex than anything it supposedly created. It doesn't explain anything -- it just shuts up questions about the "origin" by giving an answer that is impossible to analyse further. There may have been a creator. But it's impossible to make a consistent logical argument for it. And it's entirely impossible to make an argument that that creator would in any way resemble something modern mainstream religions are worshipping.
- tstactplsignore 10y ago> They found that not a single gene is shared across all of life I think this is a pop-science misunderstanding of what the authors were trying to say. They couldn't find a single unique "minimal set" of genes- but there are genes that we know all organisms share, like the rRNA genes and homologous core ribosomal proteins. All organisms will also require some kind tRNAs and their genes from some source, even if the tRNA genes themselves are not highly homologously conserved.
- julienchastang 10y agoExactly. The rRNA peptidyl transferase loop is conserved throughout all life, for example. Like, you say the researchers obviously understand this, but author of the article likely did not.
- ThomPete 10y agoThere is a great book written 20 years ago by Steve Grand called "Creation: Life and how to make it"[1] it basically uses the game Creatures[2] as the testing environment for creating Artificial Life. There are some great thoughts in that book also about how science needs more cross disciplinary experts to connect the dot's between insights in one field and apply it to others. [1] https://www.amazon.com/Creation-Life-Make-Steve-Grand/dp/0674011139 https://www.amazon.com/Creation-Life-Make-Steve-Grand/dp/067... [2] http://creatures.wikia.com/wiki/Creatures http://creatures.wikia.com/wiki/Creatures
- alfiedotwtf 10y ago> As @sixQuarks has already written, finding the minimal amount of genes when there are 175 unknown ones and you don't know anything about their dependencies and relationships seems to be pretty much impossible. Is there any way at all at simulating the tests? I'd like to apply metaheuristics to search for which combinatorics work
- smaddox 10y agoThis would require a quantum chemistry simulation many orders of magnitude larger and longer than what we currently capable of simulating. Though I suppose you could in principle use heuristics to greatly reduce the conputational complexity.
- amelius 10y ago> That's the most interesting point to me, I deeply believed that organisms share the same basic set of genes. Yes, isn't there a universal gene that encodes the RNA polymerase enzyme? I.e., the machinery that transcribes DNA into RNA?
- dnautics 10y agoprobably the ribosomes and tRNAs are the most universal-ish genes. RNA Pol is very diverse across clades.
- naasking 10y ago> That's the most interesting point to me, I deeply believed that organisms share the same basic set of genes. It should seem obvious in retrospect. Turing machines have many incarnations as different instruction sets in modern CPUs. I don't see why cells wouldn't have analogous multiple expressions, unless your deep belief was that there was only one way for protein chains to replicate.