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Biotech Science

First DNA Molecule Constructed from Mostly Synthetic Components 188

ScienceDaily is reporting that Japanese chemists have created the world's first DNA molecule comprised of almost entirely artificial components. The breakthrough could lead to advances in both medicine and technology, possibly utilizing the massive storage capacity of DNA. "In the new study, Masahiko Inouye and colleagues point out that scientists have tried for years to develop artificial versions of DNA in order to extend its amazing information storage capabilities. As the genetic blueprint of all life forms, DNA uses the same set of four basic building blocks, known as bases, to code for a variety of proteins used in cell functioning and development. Until now, scientists have only been able to craft DNA molecules with one or a few artificial parts, including certain bases."
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First DNA Molecule Constructed from Mostly Synthetic Components

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  • Re:Whoopee! (Score:3, Informative)

    by Anonymous Coward on Monday July 07, 2008 @01:10PM (#24085899)

    RTFA, they created a new stable DNA molecule with four bases that are each similar to but different from the bases found in natural DNA.

  • by Red Flayer ( 890720 ) on Monday July 07, 2008 @01:16PM (#24086005) Journal
    I know it's nitpick-y, but

    As the genetic blueprint of all life forms, DNA uses the same set of four basic building blocks, known as bases, to code for a variety of proteins used in cell functioning and development.

    This isn't quite true. DNA is the genetic blueprint for all cellular lifeforms. There are RNA viruses, there are prions... neither of which use DNA as their genetic blueprints.

    And to get really nitpick-y, it's incorrect to say that DNA uses the same set of four building blocks. It would be "more" correct to say that DNA uses a set of four building blocks. I mean, it'd be rather ridiculous if every lifeform on the planet had to share just four molecules.

    But, it's not as if we should expect an article geared towards an ignorant public to be completely accurate... the gist was captured.

    Anyway, I think I just managed to pedantically get "the Mondays" out of my system... sorry for the rant.

  • by clonan ( 64380 ) on Monday July 07, 2008 @01:16PM (#24086013)

    They can...but you wouldn't want to.

    Silicon also has 4 bond sites which you need for the complex chemistry of life. You can make identical molecules except switch silicone for carbon.

    But life will almost certainly NOT do this elsewhere.

    Silicon chemistry takes more energy than carbon chemistry.

    As an example I will point to earth. Silicone is hundreds of times more common than carbon in the crust yet life did not evolve to use Silicone, it instead used the less common carbon.

  • by backslashdot ( 95548 ) on Monday July 07, 2008 @01:18PM (#24086041)

    What "it's sequential at the base level" have to do with anything? Even in a database once you get to the address of a specifc blob of data .. you need to read off a sequence of characters right.

    Unless you mean that to access a specifc data region the DNA must be read sequentially? So if a cell needs to make a protein from say the middle of a chromosome it has to unravel and read through the entire chromosome?

    I don't think so.

    When a protein is needed, a transcription factor is used that attaches to a specific promoter region address which contains the code for the RNA (protein recipe) it needs to synthesize. The transcription factor has ways of zeroing in on the right location.

    http://en.wikipedia.org/wiki/Transcription_factor [wikipedia.org]
    http://en.wikipedia.org/wiki/Promoter_site [wikipedia.org]

  • Re:Whoopee! (Score:1, Informative)

    by clonan ( 64380 ) on Monday July 07, 2008 @01:19PM (#24086075)

    Yes, it's been done for 20 years.

    Using alternate nucleotidtes is a usefull way of creating random mutations during PCR. I have personally used these in some lab experiments in college.

    It IS true that there is no record of anyone creating a stretch of DNA with exclusivly alternate bases. This is not because of a technical limitation but because there is no practicle use for doing it.

  • Stress on base pairs (Score:4, Informative)

    by Orleron ( 835910 ) on Monday July 07, 2008 @01:20PM (#24086083) Homepage
    I don't think the summary stresses the base pairs enough. We have been able to synthesize DNA from the regular naturally occurring base pairs for a long time. This article is special because it talks about synthesizing DNA from unnatural base pairs, which several labs are working on, albeit with bacteria not chemical synthesis.

    I also detect that some folks may not understand the implications. Right now the given combination of natural DNA base pairs can only code for the 20 base amino acids used in nature. If we could create a DNA system that can code for other types of amino acids (in addition to or instead of), we would be able to make some very interesting proteins that would do gods know what, but would make for some great possibilities.

  • by burris ( 122191 ) on Monday July 07, 2008 @01:21PM (#24086099)

    This isn't a case of synthesizing familiar, natural DNA from scratch. That's been done for years and this research was done on commercial equipment for doing so. These researchers created a new type of DNA using four bases that are each similar to but distinct from the four bases that are found in natural DNA. A new chemistry basically. The article suggests that previous attempts had been unstable but this one is not. This could lead to advances like creating DNA molecules with more bases, to increase the density of storage, or find chemistries that are particularly amenable to manipulation, or who knows what.

  • Doesn't anyone RTFA? (Score:5, Informative)

    by mck9 ( 713554 ) on Monday July 07, 2008 @01:24PM (#24086143) Homepage

    No, this isn't ordinary DNA produced by synthetic means. If that were the case, it would be of little interest to anyone but a few specialists.

    What's new is that THIS synthetic DNA uses a different set of bases. not the usual C, G, T, and A.

    Presumably, therefore, it cannot usefully be read or replicated by the usual cellular machinery. That incompatibility makes it, arguably, less of a biohazard (or maybe more of a biohazard, since it might bind to the cellular machinery and gum up the works).

    The potential applications for this synthetic DNA apparently involve using it as a structural component of nanostructures. Theoretically it could be used for high-density data storage, though it's hard to imagine how the information could be either written or read.

  • Re:Whoopee! (Score:4, Informative)

    by crmarvin42 ( 652893 ) on Monday July 07, 2008 @01:26PM (#24086161)
    It's obvious that you didn't read the article and that for some reason those with mod points haven't either (as evidenced by the 3 previous responses to your post being modded down despite attempting to correct your mistake).

    They created a DNA like molecule with out using the four molecules cytosine, guanine, adenine, and thymine. Now, I don't really see any immediately obvious applications for this new molecule, but it proves to me that it is possible for life to have evolved a similar information storing mechanism distinct from the one used by all life on earth and that is interesting.
  • Re:Whoopee! (Score:5, Informative)

    by Sockatume ( 732728 ) on Monday July 07, 2008 @01:31PM (#24086221)
    You seem to conflate several rather mundane processes without having a clue what they are or how they relate to the story at hand. Also FYI DNA is not just "sugars"

    PCR, the polymerase chain reaction, takes a quantity of DNA and "multiplies it" so you have more to work with Everything in your jar is replicated blindly.

    DNA fingerprinting chops up a mixture of DNA strands at specific base sequences, then the resultant mulch is labelled (radioactively or otherwise) at other specific base pair sequences, and the whole mess is sorted by fragment size to produce a unique fingerprint. Again, this is a blind process.

    DNA sequencing allows one to obtain the sequence of bases in a DNA strand by a process tangentally related to DNA fingerprinting, but far more time consuming and finnicky as you want to make sure you're sequencing the right stuff.

    Actually building a DNA single strand, with a specific sequence of perhaps six nucleotides, from raw feedstocks, was until fairly recently a nightmarish process involving umpteen protective groups and studying it caused me to swear off organic chemistry for good. Fortunately there are much simpler automated processes available but of course that wouldn't have made for a very challenging university module.

    However, those oh-so-efficient processes are optimised for oligonucleotide chains of your common or garden five NA bases. This team have created a DNA double-helix using entirely synthetic bases which is a pretty novel thing IMO.
  • by ComaVN ( 325750 ) on Monday July 07, 2008 @01:50PM (#24086521)

    Viruses and prions are not, generally, considered to be alive.

  • I don't normally nitpick, but you made the same confounding error multiple times in one post: silicon and silicone are two different things. One is a chemical element, the other is a group of polymers which contain the element.
  • by Bowling Moses ( 591924 ) on Monday July 07, 2008 @02:04PM (#24086675) Journal
    IIRC the first chemical synthesis of a gene was by Khoran in 1970. What these guys have done is replace the four bases of DNA with different ones, and with a different attachment to the ribose group (having a carbon-carbon triple bond instead of normal DNA's carbon-nitrogen single bond), and have demonstrated double-stranded helix formation. The phosphate deoxyribose backbone is still present in it's usual way. Other groups have modified the backbone of DNA; probably the most famous is peptide-nucleic acid where the backbone is like that of a protein backbone. Also non-standard bases have been introduced by many groups and have been used for years. The paper in the Journal of the American Chemical Society also references these modifications plus some others, notably work simultaneously replacing bases and modifying the sugar groups in the backbone. Still replacing all four bases, changing the base-ribose linkage, and having the resulting product form right-handed duplexes, all of that at the same time, that's pretty cool.
  • by structural_biologist ( 1122693 ) on Monday July 07, 2008 @02:52PM (#24087319)

    As other readers have noticed, the authors of this study have used existing DNA synthesis technology to incorporate non-natural bases into DNA. While it is impressive that the authors could design bases with the correct geometry to support a DNA-like double helix, the chemistry is not too novel. However, the ability to customize DNA-like polymers has a few interesting applications.

    First, all of the sci-fi applications involving artificial life are not really feasible because one would have to design a huge number of new enzymes to recognize these artificial bases. As the field of enzyme design is still in its infancy, I do not see this happening anytime soon.

    The real applications come from non-biological uses of DNA. As previous commenter have noted, biotechnologists are investigating the use of DNA as a tool for computation/data storage. Doi et al. have designed their DNA-like scaffold such that other researchers could relatively easily construct new nucleotide pairs in order to expand the number of nucleotides used in the helix. This ability to expand the number of nucleotides could aid researchers in performing calculations using DNA.

    Another application involves DNA nanostructures (such as the "DNA origami" designed by Paul Rothemund [caltech.edu]). DNA is useful for creating nanostructures because it can be easily programmed for self-assembly into arbitrary structures (such as happy faces or long six-helical nanotubes). However, biology is full of enzymes that can degrade DNA, limiting its usefulness. As the authors of this study note, these artificial DNA molecules are resistant to degradation by natural enzymes. Furthermore, it may be possible to alter the mechanical properties of the artificial DNA by tailoring the strength of base-pairing and stacking of the non-natural bases. This could give researchers much greater control over the properties of their DNA nanostructures. One disadvantage of these artificial DNA molecules over natural DNA molecules would be the fact that it is much easier to produce long molecules of natural DNA (the non-enzymatic DNA synthesis technologies used to create the artificial DNA have difficulty creating long [>100bp] strands of DNA). Another caveat is that the authors of the study did not provide a crystal structure of the DNA so we don't yet know its true 3D structure (i.e. whether it forms a helix with the same geometry as regular DNA, although a different geometry could also be interesting).

    A real significant advance for DNA nanostructures would be an artificial DNA-like polymer that incorporates a non-natural sugar-phosphate backbone. DNA nanostructures are not stable outside of water which limits their possible applications, in part because water molecules help to stabilize the structure of the sugar-phosphate backbone. Designing a DNA nanostructure that retains its properties outside of water would be a huge boon to the field.

  • by FunkyELF ( 609131 ) on Monday July 07, 2008 @02:56PM (#24087365)
    I remember that. I didn't RTFA but what you're talking about is DNA computing, not DNA storage. The traveling salesman problem worked with a very, very small graph. I don't remember if the graph was even weighted. Anyway, when you analyze what was going on, they basically did a brute force search which wasn't even guaranteed to find the solution (except for statistics). They basically randomized a ton of DNA which they hoped represented every permutation of the cities the salesman could travel. Then they used a bunch of filters to find the shortest one that started and ended where they wanted.

    So, the method they used was brute force, just massively parallel, but with no guarantee that all permutations were created. It didn't reduce its complexity from NP.
  • Re:Whoopee! (Score:4, Informative)

    by Rutulian ( 171771 ) on Monday July 07, 2008 @04:46PM (#24089143)

    It hasn't been known for a long time. It's been known that a stable DNA helix can tolerate an aberrant base pair from an alternate nucleotide (maybe introducing a slight kink in the minor groove). However, entire oligonucleotides from alternate bases with complementarity and association into duplexes has definitely not been done before. Ever since the structure of DNA was determined it has been theoretically possible to create artificial helices, but that is different from actually doing it. This is some very nice work.

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