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Biotech Science

Reprogrammed Bacterium Speaks New Language of Life 141

Posted by Soulskill
from the already-available-in-google-translate dept.
wabrandsma writes "New Scientist reports that 'A bacterium has had its genome recoded so that the standard language of life no longer applies. Instead, one of its words has been freed up to impart a different meaning, allowing the addition of genetic elements that don't exist in nature. ... The four letters of the genetic code are usually read by a cell's protein-production machinery, the ribosome, in sets of three letters called codons. Each codon "word" provides instructions about which amino acid to add next to a growing peptide chain. Although there are 64 ways of combining four letters, only 61 codons are used to encode the 20 amino acids found in nature. ... The three combinations left over, UAG, UAA and UGA, act like a full stop or period – telling the ribosome to terminate the process at that point. ... A team of synthetic biologists led by Farren Isaacs at Yale University have now fundamentally rewritten these rules (abstract). They took Escherichia coli cells and replaced all of their UAG stop codons with UAAs. They also deleted the instructions for making the release factor that usually binds to UAG, rendering UAG meaningless. Next they set about assigning UAG a new meaning, by designing molecules called tRNAs and accompanying enzymes that would attach an unnatural amino acid – fed to the cell – whenever they spotted this codon."
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Reprogrammed Bacterium Speaks New Language of Life

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  • >Although there are 64 ways of combining four letters

    4*4*4*4 = 256

    eh?

    • Or did they mean 3 letters of four symbols?

      4*4*4 = 64.

      But that's not what the article said. Bad article.

    • Re:4^4 (Score:5, Informative)

      by pauljlucas (529435) on Saturday October 19, 2013 @02:58PM (#45176113) Homepage Journal

      4*4*4*4 = 256 eh?

      64 ways of combining four letters taken 3 at a time to form a codon.

      • Sorry, I made the mistake of reading what it said, not what it meant.

        • by oobayly (1056050)

          But you didn't. If you read what it said you would have:
          26x26x26x26 = 456,976

          Assuming you have 26 letters in your alphabet. Irish has less, German has more.

          • by Fjandr (66656)

            But there aren't 26 letters in the DNA alphabet. There are 4.

            • by oobayly (1056050)

              But the summary didn't say DNA alphabet, I thought we were reading the summary completely literally without taking into account any context.

        • by mspohr (589790)

          Reading comprehension is hard... this summary is not clearly written but it is accurate.

          • Agreed, reading comprehension is harder than it sounds, however the summary does say. " there are 64 ways of combining four letters". The first time I read the summary my brain auto-corrected it to "three" without letting me know. I had to go back and re-read the summary to see where the first post got 4^4 from.
            • PS: I read the author's intended meaning, but the statement is very ambiguous,there's really no right/wrong way to read it. It could be fixed by changing it to something like "There are 64 ways to arrange 4 letters into codons". Reading comprehension is a valuable skill but so it clear expression. A well written piece has the ability to communicate concepts accurately and unambiguously to a broad range of comprehension skills (even if it's aimed at a specialised audience).

              But let's not be too harsh, Slas
        • Sorry, I made the mistake of reading what it said, not what it meant.

          That's ok, you'll just evolve to do better next time.

    • I see you didn't even make it through the summary. Good form.
    • by KalvinB (205500)

      Note that the only examples of words had 3 letters.

      4^3 = 64

      So what they meant to say was that there are only 64 ways of combining four letters in 3 letter words.

      • If you had an infinitely long one of these, it would be kind of like a Turing machine.

        • Re:4^4 (Score:5, Funny)

          by drkim (1559875) on Saturday October 19, 2013 @03:28PM (#45176343)

          If you had an infinitely long one of these, it would be kind of like a Turing machine.

          If you had one three billion long you could have Turing himself.

          • Well, if you only had one of them, you would only have a very tiny bit of Turing himself.

            • Well, if you only had one of them, you would only have a very tiny bit of Turing himself.

              Well, his mommy had only that much at one point. Fortunately, it was capable of self replication :P

            • by drkim (1559875)

              Well, if you only had one of them, you would only have a very tiny bit of Turing himself.

              It's f-ing TURING dude!

              Code includes a "do - until" replication loop.

          • Re:4^4 (Score:4, Insightful)

            by turbidostato (878842) on Saturday October 19, 2013 @10:18PM (#45178427)

            "If you had one three billion long you could have Turing himself."

            Not as interesting. We already know that Turing halts.

            In 1954.

            • by drkim (1559875)

              "If you had one three billion long you could have Turing himself."

              Not as interesting. We already know that Turing halts.

              In 1954.

              That wasn't a error halt. Turing code correctly detected hostile external attacks and shut itself down to avoid further damage.

              Plus - this would be TURING 2.0 !

    • Re: (Score:3, Interesting)

      by mikael (484)

      Codons are sets of three letters. Every creature has its own unique codon table - every three letters (GATC) make up one codon, so there are 64 possibilities. But the fun thing is that many codons actually code for the same amino acid, but take different times to complete the process. Either because some molecular rotation is taking place or just because it's a time delay to allow folding to complete elsewhere. Then sometimes the sequence is used in reverse order (creating a back-to-front version of whateve

      • Re:4^4 (Score:4, Informative)

        by quantumghost (1052586) on Saturday October 19, 2013 @06:26PM (#45177327) Journal

        Codons are sets of three letters. Every creature has its own unique codon table - every three letters (GATC) make up one codon, so there are 64 possibilities.

        Almost. Every species has its own take on tRNA codong, but there is a lot of similarity up to the Kingdom level [wikipedia.org]

        But the fun thing is that many codons actually code for the same amino acid, but take different times to complete the process. Either because some molecular rotation is taking place or just because it's a time delay to allow folding to complete elsewhere. Then sometimes the sequence is used in reverse order (creating a back-to-front version of whatever is made) and sometimes even the sequence of letters is read with an offset of one or two letters, so essentially one group of letters can code for six different chains of amino acids.

        Uh, no...not molecular rotation or time delay....this is actually more of a planned overlap [wikipedia.org]. Pretty neat how nature planned this one. And as for mRNA being converted to a protein using tRNA (tranlation [mcgraw-hill.com]), it is strict one-way encoding (5' to 3' IIRC). dsDNA (but not ssDNA) (transscription [mcgraw-hill.com]) may be read in either direction, but mRNA not so (is is very much like ssDNA)

        • by manu0601 (2221348)
          Not related too the present article, but since you seem to master the subject: how is selenomethionine encoded? There seems to exist no codon for it.
    • They don't all bind with each other :)

    • by flyneye (84093)

      " I have the secret...to life...ITSELF " --Dr. Frank N. Furter, Rocky Horror Picture Show

      This is nothing new. Many of us modify genetics for the same reasons by adding some blue, some green, some purple, some more blue, some yellow and some red.

  • labeling food food (Score:4, Interesting)

    by bob_jenkins (144606) on Saturday October 19, 2013 @03:04PM (#45176163) Homepage Journal

    I would approve of requiring labeling on food if it was produced by one of these.

    • by fahrbot-bot (874524) on Saturday October 19, 2013 @03:23PM (#45176307)

      I would approve of requiring labeling on food if it was produced by one of these.

      I'm quite sure that, some day, these things will be labeling us as food...

      • You *are* food. You just have not met the consumers yet. Just remember, when the harvesters arrive, to not board the vehicle.
      • I'm quite sure that, some day, these things will be labeling us as food...

        How very right you are, considering these things are bacteria (see: Decomposition).

    • I would approve of requiring labeling on food if it was produced by one of these.

      And yet it should be safer than regular food, if I understand correctly. There's less risk of virus infections and DNA transfer with humans (assuming it's a real risk in the first place...).

  • Cool as hell, but I'm curious as to, well... why? And has anyone thought this through?

    Okay, sounds alarmist, I know. That said, we're rapidly approachind a level in genetics where one fuckup in procedure or policy can have some really ugly repercussions. Not necessarily Resident Evil-scale ones, but possibly something fairly ugly in its own right.

    • Cool as hell, but I'm curious as to, well... why?

      Why not? Human knowledge is expanded by trying new stuff.

      And has anyone thought this through?

      Yes. Worrying about this experiment causing grey goo [wikipedia.org] is about as silly as worrying that someone tinkering with their motorcycle might accidentally cause it to escape and survive in the wild.

      On the other hand, I could be wrong.

      • Now you've done it, I'm afraid of servicing my own motorbike now. Thanks!
      • by HiThere (15173)

        Well, it couldn't cause "grey goo", as that's the result of run-amuck assemblers. But it might yield a plague that killed everyone who bit their fingernails. (Unless, of course, this is one of those strains of e. coli that's been so crippled that it can't live outside the lab. Even then ... does e. coli go in for gene swapping?)

        • by delt0r (999393)
          Yes ecoil does gene swapping.. or more accurately plasmid swapping, that then can get incorporated into its genome.
      • by delt0r (999393)
        All life *is* the result of run-amuck assemblers.

        Consider that the grey goo hypothesis requires that the assemblers need to break the laws of thermodynamics and requires advanced alchemy to work as advertised.

        Ecoli has a volume of about .6 micro meters cubed. Or 6x10^-19 m3. In optimal conditions its replicated every 20mins. Lets say 30mins. So 48 replication cycles per day. After one day of uninhibited replication we now have about 168ml of ecoli. After 2 days we have about 47 cubic kilometers. After
    • Well since the new codon requires the organism to interact with an artificial, human-supplied substance, this seems like a good way to keep manmade organisms in check. Sort of like the dinosaurs in jurassic park. Oh dear.
    • by Lehk228 (705449)
      done this way custom code will be full of stop codons and custom ribosomes wil not stop one of the stop codons, sounds to me like this would be an safety improvement over current copypasta techniques since the compiler and the code are not compatible with natural code and natural compilers
    • Cool as hell, but I'm curious as to, well... why? And has anyone thought this through?

      It's the genetic equivalent of adding the Euro sign into your system fonts.

      • It's the genetic equivalent of adding the Euro sign into your system fonts.

        That's actually a remarkably accurate analogy, if you add the Euro sign at ascii position 0x09 (aka ^I, aka HT) and modify your software (e.g. C compiler) to treat tabs as a normal character instead of whitespace.

    • by KiloByte (825081)

      You mean, editing a processor's microcode even though you don't have any documentation (because its manufacturer requires an evil NDA, etc) isn't cool?

      Understanding how it works is also a step towards reverse engineering it, and I don't need to tell you what we could do if we fully reverse engineered cell machinery.

    • by stenvar (2789879)

      I don't see anything that could go wrong. What do you believe could go wrong with this?

    • by sjames (1099)

      Your concern is part of why. They can make the organism entirely dependent on an amino acid that does not occur in nature and whose genetic code is incompatible with other organisms. If it escapes into the wild, it starves. If it trades genes with a wild organism, the gene fails (because it won't be transcribed correctly in the wild host). If it acquires a gene from a wild host, it also fails due to incorrect transcription. Because they re-purposed what is normally a stop codon, a wild bacterium would chop

      • by HiThere (15173)

        I'm not sure about:

        If it trades genes with a wild organism, the gene fails (because it won't be transcribed correctly in the wild host)

        as this sort of depends on whether the acquired gene contains the modified code.
        P.S.: I think you meant
        (because it won't be transcribed correctly in the modified host
        as we are talking about the modifed host acquiring a wild gene.

        • by sjames (1099)

          I'm also talking about a wild host acquiring a modified gene. Neither host would correctly transcribe the other's genes. Since the whole point of the exercise is to use the codon with the altered meaning, I would presume an inserted gene would include it.

          • by HiThere (15173)

            There are several stop codes. Not every gene uses the modified version. (I.e., each gene has only one stop code.) Probably most genes do NOT include the modified stop code. If they do, then they will still do what they did before (probably) but they'll also do something unexpected. I.e., the protein that is coded for will be longer than it would otherwise be, and will include the original protein at its head. It may well fold differently (almost certainly unless it's one of the proteins with an amorph

            • by sjames (1099)

              Every man-made gene in this system would contain the stop codon or several. The wild bacteria wouldn't produce the designer protein. The lab bacteria might pick up something from the wild, but they can't survive in the wild due to their need for the artificial amino acid.,/p>

              It seems at that point that it's safer than culturing wild bacteria (for example, in yogurt). The outside chance of something bad happening is nothing that wouldn't have likely happened without the designer genes and proteins.

      • by mysidia (191772)

        Because they re-purposed what is normally a stop codon, a wild bacterium would chop up any protein coded with it.

        Yes; however, think of a sequence from wild bacteria becoming embeded in the genetic sequence of the synthetic bacteria.

        The gene could be completely dormant embedded in the synthetic bacteria; but when acquired by another wild bacteria, part of the sequence containing what the acquiring bacterium will interpret as a stop codon, results in it being chopped up, and the trojan-horse gene b

        • by sjames (1099)

          However, at that point we're no longer talking about creating a super bug in the lab. It becomes something that would be at least as plausible going directly from one wild strain to another.

          Either that or it is a deliberate attack rather than the accident in the lab scenario. However, for a biological attack, there's no need to go to such extraordinary measures.

          • by mysidia (191772)

            However, at that point we're no longer talking about creating a super bug in the lab.

            There are plenty of real superbugs that have existed and plenty of things that might evolve to be superbugs someday; there is not necessarily a need for a lab to manufacture them.

            If the presence of the synthetic bacteria increases the probability of certain families of mutated genes surviving or spreading, then it opens up new paths by which superbugs might evolve.

    • "Cool as hell, but I'm curious as to, well... why? And has anyone thought this through?"

      They used to call it "genetic engineering". Up to know it's been genetic bricolage at most. It's time the discipline is up to its name.

  • by Greyfox (87712)
    Now I'm going to have to learn to program in DNA, and learn base 4. Thanks, biology! Oh well, I guess I'll probably get an anime cat-girl out of the bargain, so I'm not THAT pissed off.
    • by Anonymous Coward

      She will reject you just like real life girls do already, so don't get too excited.

  • They are creating alien life, with the potential for organisms based on alternatives to the standard set of amino acids. I have no idea what all the implications of that will be.
    • by Ubi_NL (313657)

      No you use this to incorporate nonnatural amino acids into biological production within controlled growth cultures. This results in better usage of the available chemical space, and creation of degradation tolerant peptides. Pharma companies like this.

      • the growth culture contains things required for the transcription that aren't encoded in the organisms dna? that would be less scary and interesting.
        • the growth culture contains things required for the transcription that aren't encoded in the organisms dna?
          that would be less scary and interesting.

          Unless they additionally added genetic code to produce the extra amino acid (which I don't believe we'd currently be able to, but then, I'm no geneticist), from my understanding that's exactly what they did.

    • by Svartormr (692822)

      They are creating alien life, with the potential for organisms based on alternatives to the standard set of amino acids. I have no idea what all the implications of that will be.

      It's life, Mike, but not as we know it. >:)

  • by Ubi_NL (313657) <joris&ideeel,nl> on Saturday October 19, 2013 @03:25PM (#45176319) Journal

    Sheesz people, we've been rprogramming trna to use nonnatural amino acides for over 10 years now! Theres even a few companies st up that do just that. The principle of trna modification is old, just their method is new

    • Great, except that instead of calming the paranoid naysayers, you've made them realize that you've been acting in secret for a decade and that they should be bomb the labs RIGHT NOW.
  • I get tired of having to repeat this warning every time this idea is rediscovered, but those are NOT wasted codons, and this scheme could hardly fail to cause catastrophic consequences if it gets into the wild. Over the years people have been discovering there is less and less 'junk' DNA, and everything in the code has a meaning. The stop codons are in all probability different. and someone is going to say 'oops' in a few years, when we wipe out all or part of life on earth.

    • by BitterOak (537666)

      and someone is going to say 'oops' in a few years, when we wipe out all or part of life on earth.

      We're certainly not going to wipe out all life on earth. What we might do is change all life on earth. And as has always happened in the past, something newer and better will evolve to fill the vacuum. I, for one, am excited about the new future. Hopefully it will contain something better than humans.

    • Maybe you should have at least read and understood the summary before posting. This is not about junk DNA.

    • According to my understanding of the article referred to, not a scientific peer-reviewed paper, there is a unique protein in the medium which causes the new (formerly a stop) function to include it in the dna. I oversimplify my misunderstanding of the oversimplified article, I am sure, but it appears that the stops inserted (transferred, introduced, modified, substituted, whatever the term) will fail to result in viable "dna" without this unique protein. I imagine the protein acts as sort of a "password" f

    • by Svartormr (692822)

      I get tired of having to repeat this warning every time this idea is rediscovered, but those are NOT wasted codons, and this scheme could hardly fail to cause catastrophic consequences if it gets into the wild. Over the years people have been discovering there is less and less 'junk' DNA, and everything in the code has a meaning. The stop codons are in all probability different. and someone is going to say 'oops' in a few years, when we wipe out all or part of life on earth.

      Completely agree, except that the stop codons don't have to be different. They can just be likely to have a mistranscription and having 3 of such similar nature is to guard against this and make sure transcription actually stops.

  • If I wrote a computer program to do this, it wouldn't be special. If I submitted an article to slashdot that described how I wrote a C++ program to do this, I would probably get hate mail and possible death threats by some techie loon somewhere in Texas. Why is this story special simply b/c the process was done in a different environment? If this was a story about a new technique to manipulate codon sequences, that would be one thing. But it is not.
    • If you managed to change the instruction set of your computer's CPU, I'm sure it would be Slashdot-worthy.

      • by dkf (304284)

        If you managed to change the instruction set of your computer's CPU, I'm sure it would be Slashdot-worthy.

        Reconfigurable hardware? That's been done for decades. You don't normally build a whole CPU that way because you don't get especially good gate density.

        • by Sarten-X (1102295)

          ...But also reconfigure all your software (as stored compiled on the disk) to work around the changed opcodes, and don't forget to also change any compressed executables and checksums. Then have your new operations interact directly with hardware you also designed, and do this all this work on a molecular scale, with no instruction manual.

          That's Slashdot-worthy.

        • by tepples (727027)

          But sometimes a specialized application might not need gate density. For example, RetroZone (retrousb.com) is about to release an NES-compatible video game console with HDMI output. This FPGA contains a slightly modified* 1.8 MHz 6502 CPU, a VDP compatible with the NES PPU but modified for digital RGB output, and a PSG compatible with the one in the NES CPU.

          * The NES's variant of the 6502 lacks binary-coded decimal arithmetic. Games instead use either software BCD math or convert binary to decimal when p

    • by pepty (1976012)
      Although it overlaps with previous work more than you would guess from the original post, it does extend the control scientists have over gene expression both in research and in manufacturing settings. That's worth an article in Science.
  • I had an overwhelming sense of dread when I read this (I never studied biology). Are we like like a bunch of five year olds playing with a loaded gun?
  • I'm still looking for one via á vis programming.

    Btw., last time I communicated with a bacterium
    it drove me crazy singing "it;s a small world
    after all". A drop of chlorine set me free.

  • What could possibly go wrong?
  • So we're busy creating successors for ourselves after we're done killing off our species and most others through global warming.

    After all, it's not like we'll to worry about being around to compete with these new life forms.

    We've already pretty much doomed ourselves, and we're not doing anything to even slow down the heat-death, much less correct the problem.

    • It's very unlikely that something that needs artificial amino-acids to survive will be our successors.

  • A grander plan (Score:5, Interesting)

    by Michael Woodhams (112247) on Saturday October 19, 2013 @05:49PM (#45177125) Journal

    Some years ago, when Venter's synthetic genome bacteria was created, I came up with a plan to do this on a more extensive scale.
    (1) Sequence the genome of a bacterium, and edit the genome (on computer) to use no codons ending in 'T" or "A". (The redundancy of the genetic code allows this.)
    (2) Also edit genome so that it has tRNA for the codons ending T or A which entirely change their meanings (but still using the standard amino acids.) (Transfer RNA - tRNA - are the mechanism by which the codon code is decyphered to amino acids.)
    (3) Synthesize the edited genome, and replace the genome of a living bacterium with it. Breed for a few generations, to check that all is well, and to eliminate any of the old tRNA.
    (4) Edit the genome to use entirely the new codons. Also edit replacement tRNA for the remaining codons, ending G or C.
    (5) Replace the genome of one of our modified bacteria with this one.

    Result: a bacterium which has an entirely rewritten genetic code, and is incapable of reading the old code.

    However, I don't think I was the first to think this all up. In any case, Science didn't accept my letter proposing it.

    • Re:A grander plan (Score:4, Insightful)

      by umafuckit (2980809) on Saturday October 19, 2013 @06:41PM (#45177395)

      However, I don't think I was the first to think this all up. In any case, Science didn't accept my letter proposing it.

      That's probably because these things are much easier to think up than to do.

  • I've read a lot of articles about "reprogrammed bacteria," and until this article it's never really felt 100% appropriate until this article.

  • It seems to me that the redundancy in the code allows some triplets to be more stable than others. A random change from one letter to another shouldn't be a problem as long as the new triplet codes the same amino acid. In this light I would expect very important pieces of DNA to be coded in a way that allows more variability without changing function. How or if evolution deals with this would be interesting to study.
  • I've heard the speculation that because most (but not all) the redunant codons use just the first two letters of the three and ignore the third letter. This suggests an earlier 2-letter system coding for 15 amino acids and a stop.

    I guess long ago some otpimum fitness was achieve agt three letters instead of two or four, maybe based in chemical complexitity and energety use.

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