Reprogrammed Bacterium Speaks New Language of Life

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."

Comments

4^4

[TechyImmigrant]

>Although there are 64 ways of combining four letters

4*4*4*4 = 256

eh?

Re:4^4

[TechyImmigrant]

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

[pauljlucas]

4*4*4*4 = 256 eh?

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

Re:4^4

[rebelwarlock]

I see you didn't even make it through the summary. Good form.

Re:4^4

[TechyImmigrant]

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

Re:4^4

[Anonymous Coward]

Its dumbed-down. It is not supposed to make sense. I stopped reading at "standard language of life", when googling for that phrase turned up essentially only TFA. Did I miss anything?

Re:4^4

[KalvinB]

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.

Re:4^4

[TechyImmigrant]

It's the weekend.

Re:4^4

[TechyImmigrant]

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

Re:4^4

[Anonymous Coward]

Yep. But you'll do better next time, I know. :)

Re:4^4

[drkim]

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.

Re:4^4

[oobayly]

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.

Re:4^4

[Anonymous Coward]

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

2 sentences before that it said "sets of three letters called codons". You didn't read what it said, either.

Re:4^4

[saleenS281]

It's just genome sequencing, do the details REALLY matter?

Re:4^4

[mikael]

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 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.

Re:4^4

[mspohr]

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

Re:4^4

[davester666]

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

Re:4^4

[quantumghost]

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.

Re:4^4

[pepty]

Bad article: most of the aspects discussed were first done ~10 years ago by Peter Schultz: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1299037/

Re:4^4

[quantumghost]

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

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. Pretty neat how nature planned this one. And as for mRNA being converted to a protein using tRNA (tranlation), it is strict one-way encoding (5' to 3' IIRC). dsDNA (but not ssDNA) (transscription) may be read in either direction, but mRNA not so (is is very much like ssDNA)

Re:4^4

[TapeCutter]

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.

Re:4^4

[Fjandr]

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

Re: 4^4

[mfh]

You are now a tree frog.

Re:4^4

[TapeCutter]

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, Slashdot summaries are written by amateurs, I don't mean that as an insult, I've posted a couple of my own amateur summaries. The author of this summary is probably kicking himself over his choice of words - repeat that exercise often and the quality will improve. Communication skills are not something geeks are renowned for, which is a shame since most are worth listening to. At 55 I'm still tyring to improve mine, I was in the top 5% of Aussie school kids for reading comprehension when at HS (my English teacher thought my friend and I had cheated, lol). I just assumed that meant I was good at writing too, it wasn't until I went to uni at age 30 that I realised my English teacher was right to be skeptical, my writing skills really were inadequate.

It's easy to practice what you enjoy like (say) programming, it's much harder finding enthusiasm to practice what your not so good at. In my 20+yrs experience as a software developer, this is why so many geeks have trouble communicating with "suits". They wrongly assume that what they write is comprehensible because they wrote it, and if you can't comprehend it then you must be either ignorant or a "moron".

Re:4^4

[tricorn]

4 letters (base pairs), "sets of 3 letters called codons". "Although there are 64 ways of combining 4 letters ...", in that context, is clear and correct.

Re:4^4

[tricorn]

Try "language of life", quite a few hits. It's a fairly common phrase referring to the specific encoding of amino acids into codons,
plus the stop codons. If you didn't recognize the phrase to start with, you probably shouldn't be criticizing it for being dumbed-down.

Re:4^4

[manu0601]

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.

Re:4^4

[drkim]

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

[turbidostato]

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

Not as interesting. We already know that Turing halts.

In 1954.

Re:4^4

[Anonymous Coward]

Not quite.

Then sometimes the sequence is used in reverse order (creating a back-to-front version of whatever is made)

The reverse of, say, GATCGA would be TCGATC (I assume by "reverse" you mean the corresponding strand; otherwise your remark would make little sense). The products (if we're talking about proteins) of these two sequences are not back-to-front versions, they are something completely different. Unless it's a palindromic sequence...

Re:4^4

[Anonymous Coward]

Not that I'm your parent (I'm the AC who just "siblinged" your parent), but the answer is simple—selenomethionine is not encoded at all. While you're at it reading the corresponding Wikipedia article, you may also look up the article about selenocysteine with quite interesting encoding.

Re:4^4

[drkim]

"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:4^4

[Anonymous Coward]

Excellent linked article, covers some ground, including issues of ethics and potential harm.

I'm having some trouble following this; best I can see is that the new work is making their own tRNA, rather than suppressing the existing tRNA. Otherwise it's my impression that the earlier work was more encompassing.

At any rate, given what's been done the past twenty-some years, and with this recent work added in, I get the larger impression that we're reaching the point of cook-book viruses and bacteria; we've got some recipes already, just that the results are more for demonstration than product. The relevant research itself, of course, continues.

Re:4^4

[Redmancometh]

They don't all bind with each other :)

Re:4^4

[oobayly]

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

Re:4^4

[Anonymous Coward]

See:

The four letters of the genetic code

Re: 4^4

[DrStoooopid]

with a unicorn horn

Re:4^4

[flyneye]

" 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

[bob_jenkins]

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

Re:labeling food food

[fahrbot-bot]

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...

Re:labeling food food

[Anonymous Coward]

I'm sure a lot of people will start flaming you for such a position.

However, look up the lawsuits by the pig farmers. There isn't enough non-gm food to feed the pigs and they have all but absolute conclusive proof that it *is* the gm food that is messing with their digestive systems and killing them.

Plenty of studies as well.

Considering that, there is no fucking way I want to eat gm food. It kills the food that I eat with the food they make. WTF?

Re:labeling food food

[gl4ss]

I haven't noticed a bacon shortage.

Have you?

Re:labeling food food

[Anonymous Coward]

Soulless Green, they call it.

Re:labeling food food

[pepty]

they have all but absolute conclusive proof that it *is* the gm food that is messing with their digestive systems and killing them.

Plenty of studies as well

I'll bite.

Cite?

Re:labeling food food

[SpaceLifeForm]

You *are* food. You just have not met the consumers yet. Just remember, when the harvesters arrive, to not board the vehicle.

Re:labeling food food

[Concerned Onlooker]

Here's one:

http://www.academia.edu/542384/A_Review_on_Impacts_of_Genetically_Modified_Food_on_Human_Health

Skip down to "GM DIET SHOWS TOXIC REACTIONS IN THEDIGESTIVE TRACT"

Re:labeling food food

[pepty]

Ok.

First of all: it's been debunked:

http://academicsreview.org/reviewed-content/genetic-roulette/section-1/1-2-gm-tomatoes-proven-safe/

1. No real differences were seen between groups of animals in the study. Contrary to Smith’s claims, expert pathologists stated that mild gastric erosions were seen at similar levels in both GM and non-GM fed rats (European Commission 2000, FDA 1994).

2. There is no evidence of animal deaths. The numbers and details given by Smith about rats fatalities appear to be factually incorrect, Smith may have confused the words necrosis and dead cells with animal deaths. Careful reading reveals that the regulatory record does not mention any animal deaths which surely would have been of concern had they occurred.*

Second of all: there's nothing about feeding pigs GM food in that paper.

Finally, the publisher of that article (Bentham Open) is on Beall's list of predatory publishers which charge authors to publish their papers without actually conducting any peer review to speak of. If you heard about the recent sting on predatory journals the other week*, the Open Neutraceutical Journal's sister publication, The Open Bioactive Compounds Journal, was quite willing to publish an utterly bogus cancer article, one constructed to be obviously fake to anyone with experience in the field.

With sections titles that say "GENETICALLYY MODIFIED ANIMALS AND HUMAN NUTRITION" I don't think they spend anything on copy editing either.

*Who's Afraid of Peer Review?

http://www.sciencemag.org/content/342/6154/60.full

Re:labeling food food

[fph il quozientatore]

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...).

whatcouldpossiblygowrong?

[Penguinisto]

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.

Re:whatcouldpossiblygowrong?

[Anonymous Coward]

What do you mean why... lets just go live in fireless caves so that we don't discover technologies that can be weaponized?

Re:whatcouldpossiblygowrong?

[ShanghaiBill]

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 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.

Re: whatcouldpossiblygowrong?

[potpie]

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.

Re:whatcouldpossiblygowrong?

[Lehk228]

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

Re:whatcouldpossiblygowrong?

[K. S. Kyosuke]

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.

Re:whatcouldpossiblygowrong?

[KiloByte]

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.

Re:whatcouldpossiblygowrong?

[foobar bazbot]

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.

Re:whatcouldpossiblygowrong?

[stenvar]

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

Re:whatcouldpossiblygowrong?

[heathen_01]

Now you've done it, I'm afraid of servicing my own motorbike now. Thanks!

Re: whatcouldpossiblygowrong?

[gmuslera]

We are not mature enough as culture, and the people with resources and power to produce and weaponize (or comercialize without enough/ignored testing, check tobacco) it could actually use it in big scale. That is a bad combo.

Re:whatcouldpossiblygowrong?

[sjames]

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 up any protein coded with it.

Re:whatcouldpossiblygowrong?

[Anonymous Coward]

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.

Have you noticed that NDA and DNA are the same letters in another order? You think that's a coincidence?

Now ask yourself who "the manufacturer" is.

Re:whatcouldpossiblygowrong?

[KiloByte]

NDA [...]
Now ask yourself who "the manufacturer" is.

If you mean that bearded guy in the sky, not even his clergy give a damn about his laws anymore.

Re:whatcouldpossiblygowrong?

[HiThere]

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?)

Re:whatcouldpossiblygowrong?

[HiThere]

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.

Re:whatcouldpossiblygowrong?

[sjames]

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.

Re:whatcouldpossiblygowrong?

[mysidia]

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 becoming activated.

Think of this in terms of viruses... and viral infection vectors.

A different type of organism treating the stop codon differently, might create the required conditions for a biological "Code Injection" style attack; eg SQL Injection.

Re:whatcouldpossiblygowrong?

[turbidostato]

"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.

Re:whatcouldpossiblygowrong?

[sjames]

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.

Re:whatcouldpossiblygowrong?

[mysidia]

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.

Re: whatcouldpossiblygowrong?

[delt0r]

Who are you to judge?

Re:whatcouldpossiblygowrong?

[delt0r]

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 3 days its 1.3x10^25 m3, compare to the volume of earth of just 6x10^20 m3. The same effects that prevent ecoli from unrestricted replication, apply to anything else that can replicate.

The grey goo disaster happened 3 billion years ago. Earth as we know it is the result.

Re:whatcouldpossiblygowrong?

[delt0r]

Yes ecoil does gene swapping.. or more accurately plasmid swapping, that then can get incorporated into its genome.

Re:whatcouldpossiblygowrong?

[HiThere]

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 amorphous shape).

I will agree that almost alway the inclusion would be deleterious to the micro-organism that accepted it. Those aren't the ones that would be dangerous. But the version that's more effective than usual at detoxifying poisons (i.e., antibiotics) or at digesting food (i.e., intestinal tracts) might well be dangerous. Or, of course, it might not. And it would certainly have difficulty in sharing it's modified capabilitities with any organisms that weren't expressing the modified code.

I don't think of this as a major danger, merely a new one. And I wish they were doing it with something that didn't think of people as a place to live.

Re:whatcouldpossiblygowrong?

[sjames]

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.

Re: whatcouldpossiblygowrong?

[gmuslera]

Don't matter what i judge or not. What matter is that the people behind this research take that into account or not. Remember how promising was the research on nuclear energy at the start of the last century, and how muted were the scientists trying to avoid the government to use it against people, in fact the first practical use of it was killing hundreds of thousands of civilians. Do you think that the current government or the next one won't use it as a weapon if feels that have to do it, directly or indirectly? Or even try it on humans, whichever one are the less popular by that time.

Genetics enthusiasts

[Anonymous Coward]

Does this mean geneticists just figured out how to overclock cells?

Re:Genetics enthusiasts

[drkim]

Does this mean geneticists just figured out how to overclock cells?

No. Just added custom instruction set.

Re:Scary dna werds

[Anonymous Coward]

It seems the soulless minions of orthodoxy are trying to opress your truth!

Great

[Greyfox]

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.

Re:Great

[Anonymous Coward]

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

this is amazing

[mikeabbott420]

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.

Re:this is amazing

[Ubi_NL]

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.

Re:this is amazing

[mikeabbott420]

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

Re:this is amazing

[maxwell demon]

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.

Re:this is amazing

[Svartormr]

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. >:)

Explanation

[Anonymous Coward]

codons are words composed of 3 symbols each of which can take on 4 values. 4^3 = 64

The work described here is known as amber and ochre codon replacement. it's not new. its 20 years old. I have no idea why they think this is new or newly significant, since people do this all the time. It's a commerical product.

Welcome back to 10 years ago

[Ubi_NL]

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

Re:Welcome back to 10 years ago

[Anonymous Coward]

Or many millions years back if you look at nature. It's not like all live uses the same interpretation of DNA, there have always been differences (though of course not very widespread, as once your DNA -> amino mapping is too different from the mainstream, you can longer partake in horizontal gene transfers, which means you eventually stagnate and only keep to live in some niches).

Re:Welcome back to 10 years ago

[maxwell demon]

Actually it's very widespread, as the mitochondria in every cell use a slightly different genetic code than the cell itself. So it's spread to every single cell.

Re:Welcome back to 10 years ago

[kylemonger]

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.

Re:Welcome back to 10 years ago

[Anonymous Coward]

I think these non-natural amino-acids have made it into the spelling cortex of your brain over the last 10 years.

this is a big mistake

[tbonefrog]

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.

Re:this is a big mistake

[BitterOak]

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.

Re:this is a big mistake

[maxwell demon]

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

Re:this is a big mistake

[Anonymous Coward]

I get tired of having to repeat this warning every time this idea is rediscovered, but those are NOT wasted codons

Hi, God, there's always been some other things that I wanted to ask you about if you have a moment...

Re:this is a big mistake

[Anonymous Coward]

Regarding the three stop codons as identical function is like considering two of the three codons to be 'junk'.

I disproved the notion that 'synonymous' codons were interchangeable, in 1990, just about the time 'bioinformatics' was being coined. What I disproved was the basis for Anfinsen's Nobel Prize.

Thanks for the correction. Maybe I will read the article someday.

Re:this is a big mistake

[19thNervousBreakdown]

New, certainly, but that's a tautology. Better? Always? What's your definition of "better"?

Re:this is a big mistake

[Anonymous Coward]

Thanks for the clarification. You are only going to 'change' all life on earth. Phew!!! I am very relieved, and I hope you do a few centuries of testing before implementing this change to a multi billion year old system. In case there might be a bug or something. Or at least review the documentation. I now the temptation to be a billionaire sometimes leads to overly-short testing cycles, but it is not a mature way to operate, especially when there is only one known life-harboring planet.

Re:this is a big mistake

[Anna Merikin]

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" for a successful reaction.

What do you think?

Would this make it safer?

Re:this is a big mistake

[foobar bazbot]

Well, then. If some AC says he personally disproved something, without bothering the paper he published on it, the methods used to disprove it, or basically anything else... why wouldn't everyone believe him over TFA?

Re:this is a big mistake

[Anonymous Coward]

this has been discovered many times, it turns out a few of those times were before the time I disproved it -- http://www.ncbi.nlm.nih.gov/pubmed/17914237

for example.

Re:this is a big mistake

[Svartormr]

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.

Re:this is a big mistake

[maxwell demon]

Regarding the three stop codons as identical function is like considering two of the three codons to be 'junk'.

Nice try to weasel out. "Junk DNA" is a term with fixed meaning. Also, regarding the three stop codons as being functionally identical means to mean two of them to be redundant, not "junk" (which two of the three would be the junk?). Given the similarity of the three stop codons, I'd guess the redundancy provides some protection against mutations.

I disproved the notion that 'synonymous' codons were interchangeable, in 1990, just about the time 'bioinformatics' was being coined. What I disproved was the basis for Anfinsen's Nobel Prize.

The work you did in 1990 was the basis for Anfinsen's Nobel Prize in 1972? Yeah, sure. I guess you also invented the time machine?

But nice try.

Also, if you were working in the field, you'd for sure know what "junk DNA" means.

Re:this is a big mistake

[someone1234]

If it outlives its predecessors it is better.

Re:this is a big mistake

[tbonefrog]

The only thing special about my refutation of Anfinsen in 1989, it turns out, is that it was a non-biological refutation, pssibly the first. A little statistics drawn from the meager dna and protein sequences available in 1989 (they fit on a few floppies) was enough to prove that codon choice, when there is more than one codon for an amino acid, influences the secondary structure of the protein at that loocation.

As to stop codons, if you had three halt instructions in an unknown assembly language, the decision that they are all the same and interchangeable might be assumed risky by programers, and there is biological evidence that this decision is wrong. (just google).

This would be important if the unknown assembly language was for some important program which we knew very little about and was of great consequent to our existence..

But since it's jst the genetis code, hell, lets just hack it and see what happens!

Why is this special

[Phoeniyx]

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.

Re:Why is this special

[maxwell demon]

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

Re:Why is this special

[dkf]

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.

Re:Why is this special

[pepty]

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.

Re:Why is this special

[Anonymous Coward]

Go google microcode, read up on hardware implementations of the late 1950's, early 1960's and then come back and marvel at how stupid you were when you posted this.

Re:Why is this special

[Sarten-X]

...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.

Re:Why is this special

[tepples]

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 printing.

Mutants

[Anonymous Coward]

I'm pretty sure this is eventually going to result in superpowers.

I, for one, welcome our new indestructable E Coli

[mnemotronic]

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?

That might be a bad idea...

[Anonymous Coward]

Considering what I know about standard programming, it's possible that all three of those "stops" as they're called may perform different functions. Removing one may cause buffer overflows or some other unwanted side effect.

Standard Language?

[Mister Liberty]

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.

Re:Scary dna werds

[Anonymous Coward]

I couldn't remember where I heard "souless minions of orthodoxy" before so I had to Google it. Was DS9 referencing it from somewhere else or is that the source?

missing tag:

[Ralph Spoilsport]

What could possibly go wrong?

Successors

[msobkow]

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.

Re:Successors

[marcosdumay]

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

A grander plan

[Michael Woodhams]

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

[umafuckit]

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.

Re:A grander plan

[mrchew1982]

to some degree the redundancy in the translation codons is there because the mating tRNA isn't always an exact match.

We like to think of it as a nice clean process, but in reality it's a VERY messy process involving lots of fuzzy factors and probabillities. The way that the ribosome works is by having the tRNA "crash" randomly into the opening. If it's the correct tRNA it will bond to the DNA and stay there. Ones that don't fit are repelled by molecular forces. There is such a small difference between the bonding potential of GUU and GUA that if they were assigned to different amino acids there would be many many more mistakes, resulting in miscoded proteins.

redundancy in wetware is usually there for a reason!

Re:A grander plan

[Michael Woodhams]

Thanks. I work with genetics at the applied maths/algorithms/programming end, so the biological complexities can escape my notice.

I'm not so sure about your example. While GUU and GUA are synonymous, GAU and GAA are not. The genetic code almost entirely treats codon 3rd position A/G as synonymous and U/C as synonymous. (The only exception in the 'standard' code is UGA=stop, UGG=Tryptophan.)

If we treat third position as having only two distinguishable letters, we can still make the process work, but with more generations. (I'll call this a 'reduced codon'.) We have 32 reduced codons (4x4x2) and 21 meanings (20 amino acids plus 'stop') leaving 11 to spare. So we remove 11 reduced codons from the genome by replacing them with synonymous codons, and make new tRNA for the removed codons. Breed a few generations. Recode the genome to use the 11 new reduced codons (so now genome is running on 11 new codons, 10 old codons.) Recode 11 other reduced codons to synonymous ones (the new ones from previous step) and give them new tRNA. Breed a few generations. Recode the final 10 old codons to the second set of new tRNA, and make new tRNA for those 10 codons. I.e. same process, but it takes 3 recoding steps instead of two, because we can't change as many codons at once.

Also, we'll be keeping our bacteria in a very friendly environment. It doesn't need to out compete other bacteria, just to do well enough to reproduce. We can tolerate the occasional dud protein, but if the error rate is several amino acids per protein, the bacterium won't be viable.

No

[Anonymous Coward]

There are like 500 known amino acids in nature. There are 22 standard proteinogenic amino acids. The "standard language" is actually called genetic code 1, it's but one among dozens. The summary is plain awful.

And that's

[Anonymous Coward]

how you breed Klingons........... I'm thirsty. Prune juice! Large!

stop all the anthropomorphising chemical reactions

[Anonymous Coward]

It "reads" this, and "provides instructions" and "telling it where to stop" and "giving it new meaning" and "whenever they spotted"

proteins don't read, they don't have a "rulebook" with "meanings", they don't decide or spot things

Where the fuck is the SCIENCE in this?

Von Neumann Turing?

[Guppy]

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

To Serve Man

[Guppy]

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).

Re:I, for one, welcome our new indestructable E Co

[Anonymous Coward]

Go learn some biology and overcome your ignorance, or don't, the rest of us will move on without you either way. :-)

ok fine

[Anonymous Coward]

Sure lets forge ahead. Lets make it a good thing to trade stocks faster than the other guy, instead of maing ita fair and level market. Lets worry about security less than getting to market, lets worry more about the NSA having our data than a bunch of multniational companies. i happen to think the internet has grown up enough that it needs government regulation before it starts doing things the people don't really want. tech is controlling us, not the other way around. Let's do crypto for 90% of the world of commerce based on unproven suppositions that are becoming more douubtful every month.

Yeah, get off my lawn too. Some high tech stuff at the hospital didn't work out as well as advertised six weeks ago and I'm having to process the consequences through my body, so I'll be a lot more cheerful in a few more months.

God, Schmod...

[Anonymous Coward]

I want my monkey-man.

Programming

[Redmancometh]

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

0_0

[Anonymous Coward]

Sounds like the beginning of a zombie movie

Stability of amino acids

[gr8_phk]

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.

fossil 2-codon system inside 3-codon system?

[peter303]

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.

OHS NOES!!!!

[Anonymous Coward]

ZOMBIES!!