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Minimal genome ... which also means the minimal viable cell. They are trying to figure out what is the minimal amount of genes to create a cell that can surviv

Minimal genome ... which also means the minimal viable cell. They are trying to figure out what is the minimal amount of genes to create a cell that can survive and reproduce. Craig Venter, the researcher from the Nature article, claimed to have built "artificial life" earlier in 2010. The new Nature article is reporting he's claiming to have made a "new species". An article on Venter's group's 2010 work: https://www.theguardian.com/science/2010/may/20/craig-venter-synthetic-life-form https://www.theguardian.com/science/2010/may/20/craig-venter... ... "Craig Venter and his team have built the genome of a bacterium from scratch and incorporated it into a cell to make what they call the world's first synthetic life form" The recent 2016 Science journal article is here : http://science.sciencemag.org/content/351/6280/aad6253 http://science.sciencemag.org/content/351/6280/aad6253 "JCVI-syn3.0 is a working approximation of a minimal cellular genome, a compromise between small genome size and a workable growth rate for an experimental organism. It retains almost all the genes that are involved in the synthesis and processing of macromolecules. Unexpectedly, it also contains 149 genes with unknown biological functions, suggesting the presence of undiscovered functions that are essential for life. JCVI-syn3.0 is a versatile platform for investigating the core functions of life and for exploring whole-genome design." One question I would have is "Are there homologs to the 149 unknown function genes in the human genome"?

stcredzero 11y ago
There are probably some things we don't know about the insides of a bacterium, and there are probably some fabrication techniques to be worked out, but I would expect the knowledge of how to fabricate a whole cell from scratch within a decade. (I know little of molecular biology, so this is a wild layman's guess.)
kyberias 11y ago
The original article uses these concepts interchangeably: minimal genome and minimal cell. They basically define the minimal cell as a cell with a minimal genome. E.g. "Because our minimal cell is largely lacking in biosynthesis of amino acids, lipids, nucleotides, and vitamins, it depends on the rich medium to supply almost all of these required small molecules."
- tosseraccount 11y ago
  Humans need a lot of them, too ... but , yeah, a special bacteria chow for these critters is a good idea.
- dekhn 11y ago
  I don't think it necessarily follows that a minimal genome has the minimal cell or vice versa. It really depends on how much support structure (the rich media) is provided and the specific details of how the genome produces the cell structure, and the cell structure details. One can imagine little cycles of genes that all need each other, but don't actually provide any extra fitness. IIRC the Venter method can't identify and remove those sorts of cyclic dependencies if the cycle is more than 1-2 long.
kyberias 11y ago
Oh and to answer your question, there are at least some homologs: https://d2ufo47lrtsv5s.cloudfront.net/content/sci/351/6280/aad6253/F6.large.jpg?width=800&height=600&carousel=1 https://d2ufo47lrtsv5s.cloudfront.net/content/sci/351/6280/a...
logfromblammo 11y ago
That isn't exactly "from scratch". They took pre-existing genes from a known bacterial genome (M. mycoides) and started knocking out genes via an automated process until the final resulting genome was no longer viable if any of the remaining genes were likewise removed. That doesn't quite meet my definition of synthetic life form. It's like the difference between stripping down a stock car for racing and building an entire go-kart from unrefined, unsorted piles of rock. That synthetic genome is the end product of billions of years of evolution minus billions of years of accumulated kludges and cruft. And it's about half a megabyte. It wasn't designed, but discovered. I would guess that there are plenty of genes in the sequences common to fungi, plants, and animals that cannot be removed without ruining the whole organism. Many of those would have currently unknown functions. And those 149 genes are what remain from running the cruft-removal process on one species of bacterium. To determine whether they are truly required for life, they woul have to also be retained after running the process on other species to discover their minimally viable genomes.
- SapphireSun 11y ago
  I think you guys are missing the point a bit. The important thing here is that there's a minimal genome in a working organism that can be used as a research platform. The "from scratchness" level is purely for bragging as once the cell divides a few times and fails to maintain components, it'll be working from the set of things its genome specifies. Whether you consider that cheating isn't really relevant for the potential experiments you can run. EDIT: For a CS example, imagine trying to reverse engineer a computer system and make it do things it wasn't supposed to do. It's a lot easier to tinker with hardware from an Apple ][ than with a modern x86 chip. The advance here is that we are finding the Apple ][ in the x86 chip and doing a run of those for people who want to play with them.
  - jonnathanson 11y ago
    Exactly. Furthermore, you don't need to build life from scratch. That's wasteful. You'll just set yourself back years, possibly a decade or more, trying and erring until you get to roughly the same place as the stripped-down bacterial genome at which Venter and his colleagues have arrived. Venter isn't explicitly trying to create life from scratch; he's trying to find the minimum viable platform from which to harness life for various useful purposes. Starting from the proverbial "pile of unrefined rock" would accomplish nothing but scoring a few vanity points.
hirenj 11y ago
I went to the article to try and dig up information about the orthologues, but as is kind of par for the course these days, the meat of the useful information is not readily available. If you go to the supplementary information, you can find an excel sheet with the locus and amino acid sequences for all the genes. It's then just a matter of blasting the unknown function genes against the human genome and using a cutoff for similarity. I'm going to have to wait to do this next week, but if any enterprising soul wants to do this, you can get the supplementary data here: http://science.sciencemag.org/content/351/6280/aad6253/suppl/DC1 http://science.sciencemag.org/content/351/6280/aad6253/suppl...
- sevenless 11y ago
  Looking at that supplementary Excel spreadsheet, only 42 of those essential genes are annotated as "hypothetical protein/unknown function/unclear functional category". For example, locus MMSYN1_0421 has unknown function, but belongs to the alkaline shock protein family, so we can't say we have no idea what it does. They seem to be the only loci where we're truly in the dark. There are many more with "putative" or "probable" roles and known homologs. In total the headline seems to be misleading. We're only truly lost on about 9% of these essential genes.

stcredzero 11y ago

There are probably some things we don't know about the insides of a bacterium, and there are probably some fabrication techniques to be worked out, but I would expect the knowledge of how to fabricate a whole cell from scratch within a decade. (I know little of molecular biology, so this is a wild layman's guess.)

kyberias 11y ago

The original article uses these concepts interchangeably: minimal genome and minimal cell. They basically define the minimal cell as a cell with a minimal genome. E.g. "Because our minimal cell is largely lacking in biosynthesis of amino acids, lipids, nucleotides, and vitamins, it depends on the rich medium to supply almost all of these required small molecules."

tosseraccount 11y ago
Humans need a lot of them, too ... but , yeah, a special bacteria chow for these critters is a good idea.
dekhn 11y ago
I don't think it necessarily follows that a minimal genome has the minimal cell or vice versa. It really depends on how much support structure (the rich media) is provided and the specific details of how the genome produces the cell structure, and the cell structure details. One can imagine little cycles of genes that all need each other, but don't actually provide any extra fitness. IIRC the Venter method can't identify and remove those sorts of cyclic dependencies if the cycle is more than 1-2 long.

kyberias 11y ago

Oh and to answer your question, there are at least some homologs: https://d2ufo47lrtsv5s.cloudfront.net/content/sci/351/6280/aad6253/F6.large.jpg?width=800&height=600&carousel=1 https://d2ufo47lrtsv5s.cloudfront.net/content/sci/351/6280/a...

logfromblammo 11y ago

That isn't exactly "from scratch". They took pre-existing genes from a known bacterial genome (M. mycoides) and started knocking out genes via an automated process until the final resulting genome was no longer viable if any of the remaining genes were likewise removed. That doesn't quite meet my definition of synthetic life form. It's like the difference between stripping down a stock car for racing and building an entire go-kart from unrefined, unsorted piles of rock. That synthetic genome is the end product of billions of years of evolution minus billions of years of accumulated kludges and cruft. And it's about half a megabyte. It wasn't designed, but discovered. I would guess that there are plenty of genes in the sequences common to fungi, plants, and animals that cannot be removed without ruining the whole organism. Many of those would have currently unknown functions. And those 149 genes are what remain from running the cruft-removal process on one species of bacterium. To determine whether they are truly required for life, they woul have to also be retained after running the process on other species to discover their minimally viable genomes.

SapphireSun 11y ago
I think you guys are missing the point a bit. The important thing here is that there's a minimal genome in a working organism that can be used as a research platform. The "from scratchness" level is purely for bragging as once the cell divides a few times and fails to maintain components, it'll be working from the set of things its genome specifies. Whether you consider that cheating isn't really relevant for the potential experiments you can run. EDIT: For a CS example, imagine trying to reverse engineer a computer system and make it do things it wasn't supposed to do. It's a lot easier to tinker with hardware from an Apple ][ than with a modern x86 chip. The advance here is that we are finding the Apple ][ in the x86 chip and doing a run of those for people who want to play with them.
- jonnathanson 11y ago
  Exactly. Furthermore, you don't need to build life from scratch. That's wasteful. You'll just set yourself back years, possibly a decade or more, trying and erring until you get to roughly the same place as the stripped-down bacterial genome at which Venter and his colleagues have arrived. Venter isn't explicitly trying to create life from scratch; he's trying to find the minimum viable platform from which to harness life for various useful purposes. Starting from the proverbial "pile of unrefined rock" would accomplish nothing but scoring a few vanity points.

hirenj 11y ago

I went to the article to try and dig up information about the orthologues, but as is kind of par for the course these days, the meat of the useful information is not readily available. If you go to the supplementary information, you can find an excel sheet with the locus and amino acid sequences for all the genes. It's then just a matter of blasting the unknown function genes against the human genome and using a cutoff for similarity. I'm going to have to wait to do this next week, but if any enterprising soul wants to do this, you can get the supplementary data here: http://science.sciencemag.org/content/351/6280/aad6253/suppl/DC1 http://science.sciencemag.org/content/351/6280/aad6253/suppl...

sevenless 11y ago
Looking at that supplementary Excel spreadsheet, only 42 of those essential genes are annotated as "hypothetical protein/unknown function/unclear functional category". For example, locus MMSYN1_0421 has unknown function, but belongs to the alkaline shock protein family, so we can't say we have no idea what it does. They seem to be the only loci where we're truly in the dark. There are many more with "putative" or "probable" roles and known homologs. In total the headline seems to be misleading. We're only truly lost on about 9% of these essential genes.