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First DNA Molecule Constructed from Mostly Synthetic Components

Posted by ScuttleMonkey on Mon Jul 07, 2008 11:56 AM
from the add-another-helix dept.
Biotech Science
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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  • Well it's been done for many decades. The trick is making the sequence longer & automating the process to not require an army of grad students.

  • For info storage? Nice idea in theory but... (Score:3, Insightful)

    by Viol8 (599362) on Monday July 07 2008, @12:02PM (#24085789)

    .. DNA decomposes from bactierial , chemical and radiative action so can't just be left on its own locked away for years.

    DNA is read slowly by biological means which is hardly easy to interface to digital systems.

    DNA is read sequentially , its not random access at the base level making it useless for most types of database.

    Current technologies could in theory already be pushed to have greater storage density than DNA - eg transistors made from a few atoms.

    So other than an interesting intellectual exercise , whats the point?

    • One property DNA has that transistors don't is that with some enzymes and spare base pairs it can copy itself. You can dissolve lots of copies in a liquid and spray it about to have redundancy. Whether this is useful, I don't know. I doubt that pouring a test tube of synthetic DNA into the ocean and letting it reproduce itself and diffuse around the globe will replace Bittorrent any time soon.

      • Re: (Score:3, Interesting)

        by mikael (484)

        There was article some time where the scientists demonstrated how it was possible to solve the "Travelling salesman problem". Different strands of DNA were constructed to represent the different route segments that were possible and replicated. These were all mixed up together in a container and stirred together. As they were mixed together different strands would join up.

        The solution to the problem was the shortest strand that had the starting point and ending point, along with each and every route destina

        • Re: (Score:3, Informative)

          by FunkyELF (609131)
          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 t

    • Re: (Score:3, Informative)

      by backslashdot (95548)

      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 specif

    • Perhaps computer interfaces may be a bit of a stretch, but the potential for custom DNA sequences, whether it's to make new drugs or do nanoengineering for things like solar panels or battery components, is tremendous.

      While I doubt it would work with artificial bases, since I doubt you could readily get DNA made of artificial bases to reproduce inside an organism one of my favorite potential uses for "ordinary" custom DNA sequences is to eradicate invasive species. You need to make "greedy" (parasitic gene

  • Who cares? (Score:5, Funny)

    by eln (21727) on Monday July 07 2008, @12:05PM (#24085831) Homepage

    This is nothing new...I created a DNA molecule out of entirely synthetic components for my 5th grade science fair project. Mine was made out of colorful wooden balls glued to wooden sticks. Theirs appears to be sugar-based, which would probably attract ants, so mine is obviously superior.

  • You know, because it'd be nice to know if life can be built on a different set of elements.

    • Re:Can they use silicon in place of Carbon? (Score:4, Informative)

      by clonan (64380) on Monday July 07 2008, @12:16PM (#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.

      • 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.

        • Re:Can they use silicon in place of Carbon? (Score:4, Interesting)

          by clonan (64380) on Monday July 07 2008, @01:43PM (#24087185)

          Yes...I am still convinced that carbon would rule the roost.

          In order for silicon to even remotely compete, Silicon dioxide would have to be gaseous. At the several hundred degree higher temp, large and complex molecules become unstable.

          In addition silicon is a larger atom which creates a greater limit on structures than carbon.

          Carbon would still be used with Ammonia. Using methane absolutely requires carbon (methane being a hydrocarbon).

          There is no known condition in which silicon would be preferable while still allowing for large complex molecules.

          I get annoyed when people ignore basic physics and chemistry for their own pet beliefs.

  • Entertaining Theological question... (Score:4, Insightful)

    by fuzzyfuzzyfungus (1223518) on Monday July 07 2008, @12:09PM (#24085893) Journal
    We have a sequence of a human genome and are likely to produce more in the future.
    We can, albeit presently with difficulty, construct DNA sequences from artificial materials.
    We can, in principle, produce viable eggs by nucleus transfer from one egg to another.

    If a "human" embryo is produced from synthesized DNA and by nuclear transfer into an egg from artificial or animal sources, the resulting organism will be structurally equivalent to human, without any physical connection to the human race.

    Does this organism have a soul? Is it subject to original sin?


    Angels and heads of pins aside; this is pretty cool. There is, though, a slightly unpleasant possible outcome of being able to synthesize DNA sequences. Certain viral pathogens, smallpox comes to mind, are very, very hard to get ones hands on. Samples are tightly controlled and generally not allowed out to play. This is a Good Thing. Genetic sequences, however, are public knowledge. In principle, with sufficient expertise in DNA synthesis(and some protein coating wizardry) one could just "compile" some smallpox from source and then go have a smallpox party with the nearest population center. Happy times.

  • the SAME building blocks?! (Score:4, Informative)

    by Red Flayer (890720) on Monday July 07 2008, @12:16PM (#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.

    • Re: (Score:3, Informative)

      by ComaVN (325750)

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

      • Re: (Score:3, Interesting)

        by Red Flayer (890720)
        I'd surmised the same, but haven't seen any research on this... could you steer me to some good reading on the topic?

        Thanks.

  • Now I can store pirated music in my DNA!

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

    by Orleron (835910) on Monday July 07 2008, @12:20PM (#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.

    • Re: (Score:3, Interesting)

      by comm2k (961394)
      The current 4 bases allow 64 combinations (codons). Yet they're only 20 (actually 1 or 2 more) amino acids coded by them (- stop). Introducing new bases does not overcome this limit - the limit is in the tRNAs which are complementary to more than 1 codon. You would also have to create tRNAs complementary to your new codons and for that to be efficient you would need compatible enzymes loading these tRNAs with your new amino acid.
      The latter part is actually far more work then creating this type of 'artific

  • Not Synthetic, Artificial (Score:4, Informative)

    by burris (122191) on Monday July 07 2008, @12:21PM (#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, @12:24PM (#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.

  • The mystery of "life" (Score:5, Interesting)

    by ortholattice (175065) on Monday July 07 2008, @01:02PM (#24086655)
    There is a long, long way to go before a self-reproducing organism results from a random combination of DNA, artificial or not.

    It is possible for a very simple "lifeform" with only 54 base pairs [ucr.edu] to be self-reproducing, but only if it is parasitic. Such "lifeforms" exploit the complex and sophisticated DNA machinery of the host to accomplish reproduction.

    I found it amazing that the simplest known lifeform that can reproduce independently is the Mycoplasma genitalium bacteria [wikipedia.org], with 582970 base pairs! This probably isn't the simplest one that can theoretically exist - it is hard to imagine the right combination out of 4^582970 appearing at random in the pre-life organic soup - but whatever simpler thing existed before it is a mystery, as well as why none of the simpler forms still exist today (if that is the case).

    This has been bugging me for some time, and as far as I can tell no one has a good answer.

  • still cool, but a bad summary. (Score:4, Informative)

    by Bowling Moses (591924) on Monday July 07 2008, @01:04PM (#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.

    • Re: (Score:3, Informative)

      by Anonymous Coward

      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.

        • Given the journal it's in, there must be something notable about this work. I had the same reaction as you, though.

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

                  by Rutulian (171771) on Monday July 07 2008, @03:46PM (#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.

        • Re:Whoopee! (Score:5, Interesting)

          by pesho (843750) on Monday July 07 2008, @01:05PM (#24086681)
          Dude, _read_ _the_ _fucking_ _article_! Their bases are not the stuff you can buy from the store. Look at the structures, they are not even going to pair with the regular bases. Their iG:iC pair uses DDA (donor, donor, acceptor) sequence of hydrogen bonds instead of ADD in the normal G:C pairs. I'll be surprised if you used similar 'alternate nucleotides' for the 'past 20 years' to 'create random mutations'. There is a practical use for these and is not for making 'random mutations'. Having alternative to DNA and RNA is one of the prerequisites in creating synthetic organisms with different genetics and biochemistry. Imagine starting the the evolution from scratch, or creating microbes for industry that can't exchange genetic information with the rest of the living organisms on earth.

          • Re: (Score:3, Interesting)

            by clonan (64380)

            I work in pharmaceuticals. I am constantly shocked by what random chemicals someone has in stock just sitting there.

            Just because you can't buy them from a drug store doesn't mean it isn't readily availible (for the right price)

          • Since you guys seem to be very "up" on this "DNA" stuff, I shall posit a question...

            From the Apex of my complete ignorance about Synthetic DNA, does this discovery mean I should:

            A) Begin stocking up on weapons, ammunition and food in a highly defensible bunker for the inevitable Solanum virus outbreak and subsequent zombie horde plague.

            B) Begin boning up on my virtual gaming ability as our new Synthetic DNA Overlords encapsulate all of humanity in a virtual world until such time as The One frees us all.

            C)

            • No need to worry. The *cough* synthetic DNA is right-handed. You can't eat *cough* it and it *cough* can't *cough* *cough* it can't *cough* *cough* it it *cough* *graack* *graaaaaack*

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

      by crmarvin42 (652893) on Monday July 07 2008, @12:26PM (#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, Interesting)

        by clonan (64380) on Monday July 07 2008, @12:33PM (#24086263)

        Ummm...that alternate nucleotides were possible was proven 30 years ago. Synthetic DNA was only created 20 years ago.

        While the 4 bases used do have some advantages in sysntesis, stability and other effects, tehre is no compelling reason that requiers thoes 4 bases.

        I have no idea how this got published...The reason a similar article hadn't been published earlier is because every reputable scientist in the field agrees with you:

        Now, I don't really see any immediately obvious applications for this new molecule

        This article did nothing to expand our knowledge. It didn't prove anything. All it showed is that the machine they ALREADY had in the lab could do everything the manual they got with it said it could.

        BTW, I don't see any responses modded down like you suggested...

        • Despite my not doing a lot of genetics work myself, I did know that synthetic NA's had been developed and used, but I was under the impression that they were normally used as a substitution for a single NA for reasons of causing/preventing mutations. I got the impression from the article that these new NA pairs wouldn't work with normal DNA, but I may have misinterpreted what the article said.

          The initial post made it sound as though they were talking about creating a normal DNA strand from scratch which

          • Hmm, I can't see any negative mod points on any of thoes posts and new modding doesn't change the history.

            I bet thoes people have poor Karma and so they aren't given free points when they post.

            As for designing complementary nucleotides, yes that is slightly more difficult....However I had the capability of doing it 10 years ago with a piece of chemistry modeling software that requiered for every freshman at my school. After you have complementary chimicals you could probably just order them from a catalogu

        • Re: (Score:3, Insightful)

          by Sockatume (732728)
          "no idea how this got published... a similar article hadn't been published earlier"

          I think you answered your own question there. Shockingly, they published a paper about something which, to the best of everybody's knowledge, hadn't been done before. Maybe you're sitting on 20 years of groundbreaking research which has created whole artificial chromosomes, but have chosen not to publish. You can hardly blame the rest of the research community for getting on with their lives and publishing what they've done

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

            by clonan (64380) on Monday July 07 2008, @01:31PM (#24087051)

            First: C-Nucleosides are nothing new and are readily availible in catalogues

            Second: Life already uses a wide variety of non-coding nucleotides typically created through post synthesis modification. One example of post synthesis modification used to control coding is methylation.

            Unfortunetly, Slashdot lack of imagination and narrowmindedness when it comes to anything has lead to an automatic acceptance of everything as "neat." This is an example of wasted research money that did not creat new information and has not lead to any new insights into nature.

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

              by xigxag (167441) on Monday July 07 2008, @02:20PM (#24087705)

              Unfortunetly, Slashdot lack of imagination and narrowmindedness when it comes to anything has lead to an automatic acceptance of everything as "neat."

              It seems to me that you are the one being narrowminded here. Clearly you are knowledgeable on the subject. But to utterly dismiss a research project on the grounds that it seems vaguely like something you did 20 years ago, and you can't see any immediate right-away 2008 benefits forthcoming, I don't know. Do you really believe with such certainly that this research project was a waste or did you argue yourself into a corner and now don't wish to back off from your absolutism?

              Frankly, even if this project is derivative and doesn't advance the science in any great measure, I still think it qualifies as "neat." Just as neat as another Firefox nightly or a new version of Ubuntu or some home-brew programming language. Does everything have to advance the sciences to be interesting? Well then, how about this: "Furthermore, the artificial DNA may be a superior building scaffold for constructing nanostructures of materials interest because of the stable C-nucleosides against ubiquitous naturally occurring enzymes such as DNase." Isn't that reason enough?

              • Re: (Score:3, Insightful)

                by clonan (64380)

                My objection is not that this isn't "neat." I am always looking out for stuff like this.

                My objection is that it was published in a peer-reviewed journal! This type of article deserves to be on the discovery channel or scientific American magazine, NOT in a legitamet scientific journal.

                If the artuicle had been about building nanostructures and they had to develop this process to do it that is one thing. But this is the equivalent of saying "I have one rock stacked on another...this may or may not be usefu

    • Re:Whoopee! (Score:5, Informative)

      by Sockatume (732728) on Monday July 07 2008, @12:31PM (#24086221) Homepage
      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.

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

        by clonan (64380) on Monday July 07 2008, @12:46PM (#24086443)

        Actually, I made a living for a number of years doing research with PCR.

        I sited DNA fingerprinting because it is a process that most people have heard of that uses PCR. Notice I said it was an example. My post was intended for those people WITHOUT advanced degrees in Biology/Chemistry. If you would like to talk about annealing temperatures, extension times, point mutations, hair-pin turns or anything else let me know.

        You are also right, DNA is not just sugar. It also includes the base and the phosphate group. However my snide remark is still valid. You are not talking about unusual chemistry. I am willing to bet good money that every component was readily available already.

        This team did nothing novel. As you pointed out, there are automated processes to manufacture short chain nucleotide chains. These machines are already capable of including single point mutations of non-typical nucleotides. All they did is fill up the machine with there off the shelf chemicals and hit go. They then re-ran the program but in reverse. When they mixed the two batches together....DNA molecules!

    • Create an egg with Mostly Synthetic Components...

      It's mostly harmless.

    • I'm more interested in the name of the researcher. They're apparently from Japan, but "Inouye" is almost, but not quite a Japanese name. Looks like they got it wrong. "Inouye" can't exist in the Japanese language (they have fewer phonemes than English). Perhaps they meant "Inoue" or "Inoe" (with a bar over the o, slashdot isn't unicode).

      • I sure hope (s)he's from a non-English-speaking country... getting through grade school would be hard with a name like "annoy".

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