Triple Helix — Designing a New Molecule of Life

Anti-Globalism sends in this quote from Scientific American about attempts to synthesize molecules that function as well or better than the natural building blocks of life: "A molecule that some researchers study in pursuit of this vision is peptide nucleic acid (PNA), which mimics the information-storing features of DNA and RNA but is built on a proteinlike backbone that is simpler and sturdier than their sugar-phosphate backbones. ... Many studies have demonstrated PNA's suitability for modifying gene expression, mostly in molecular test-tube experiments and in cell cultures. Studies in animals have begun, as has research on ways to transform PNA into drugs that can readily enter a person's cells from the bloodstream. ... Some scientists have suggested that PNAs or a very similar molecule may have formed the basis of an early kind of life at a time before proteins, DNA and RNA had evolved. Perhaps rather than creating novel life, artificial-life researchers will be re-creating our earliest ancestors."

Comments

Sounds like razors

[Daimanta]

Soon we will have the "quatro helix DNA" and then 5 helixes and so on.

Re:Sounds like razors

[Anonymous Coward]

That pretty much sums it up.

Attempts to create novel "life forms" using this rather than DNA are not coming any time soon. We can't even make life forms de novo using the established DNA codons.

Re:Sounds like razors

[sentientbeing]

Would someone tell me how this happened? We were the fucking vanguard of genetics in this country. The double helix was the DNA strand to own. Then the other guy came out with a 3 HELIX STRAND. Were we scared? Hell, no. Because we hit back with a little thing called the DNA Turbo. That's three helixes and an aloe strip. For moisture. But you know what happened next? Shut up, I'm telling you what happened--the bastards went to four strands. Now we're standing around with our cocks in our hands, selling three DNA strands and a strip. Moisture or no, suddenly we're the chumps. Well, fuck it. We're going to five helixes. Sure, we could go to four helixes next, like the competition. That seems like the logical thing to do. After all, three worked out pretty well, and four is the next number after three. So let's play it safe. Let's make a thicker aloe strip and call it the Mach3Super DNA Turbo. Why innovate when we can follow? Oh, I know why: Because we're a business, that's why!

Re:Sounds like razors

[somnolent49]

What part of this don't you understand? If two helixes are good, and three helixes are better, obviously five helixes would make us the best fucking dna that ever existed. Comprende? We didn't claw our way to the top of the dna game by clinging to the two-helix industry standard. We got here by taking chances. Well, five helixes is the biggest chance of all. Here's the report from Engineering. Someone put it in the bathroom: I want to wipe my ass with it. They don't tell me what to inventâ"I tell them. And I'm telling them to stick two more helixes in there. I don't care how. Make the helixes so thin they're invisible. Put some on the RNA. I don't care if they have to cram the fifth Helix in perpendicular to the other four, just do it!

Er.

[Futile Rhetoric]

If PNA functions "as well or better", then what exactly was the reason that RNA and DNA evolved in the first place?

Re:Er.

[Adambomb]

Don't make the mistake of anthropomorphizing evolution. There is no committee that considers all possible solutions and states "This is the best one". Evolution is a case of what happens happens and what doesn't die out is what's left and so considered successful.

It is entirely possible that there are much more efficient ways for life to exist or function, but are different than the way life happened to happen here on earth. Or it could be that life DID happen that way but the methodology was not optimal for the environment at the time so the DNA/RNA based forms outlived them.

Re:Er.

[dfm3]

Possibly because evolution requires a molecule that is not too stable.

I'm just speculating here... the basis of evolution is random changes in DNA which result in a phenotype which may confer an advantage to one individual over another. If you have an absolutely error-proof system of DNA replication, you effectively limit evolution. But you don't want too many changes at one time, which would actually be detrimental. The ideal balance is somewhere in between... and it may be that a DNA double-helix with a sugar backbone is the ideal molecule for allowing just the right frequency of random changes for evolution to progress.

Re:Er.

[spud603]

There's nothing in evolutionary theory that says that natural selection results in 'progress'. Nothing that says that homo sapiens are more 'progressed' than neanderthals. Same goes for elephants vs woolly mammoths. This is one of the biggest and most frustrating misconceptions out there about evolution by natural selection. I think this is what GP was referring to when mentioning anthropomorphization -- don't apply human rationality to evolutionary processes.

That said, I agree that it seems unlikely that such a fundamental shift as switching from PNA to DNA/RNA seems unlikely to have fluked itself into existence unless there's some tradeoff in, eg, efficiency of producing the molecules, or the difference is really pretty minor after all.

Re:Er.

[Futile Rhetoric]

How is "evolutionary progress" not "progress"? This is the only measuring stick I've used. If PNA had indeed existed before DNA or RNA (as the article seems to suggest), and was snuffed out, then clearly it didn't function better than RNA/DNA when it came to surviving in a particular environment, or evolving. What is the "functionality" of an organism if not survival and procreation?

Re:Er.

[Adambomb]

in a particular environment, or evolving

This is the exact point i'm trying to make that you seem to be missing. Survival in a particular environment does not mean a life form is best at surviving in any environment. If there was a long enough period where the stimuli and environmental pressures involved made RNA/DNA based life the most efficient, then there would be none of the alternative life forms remaining when the pressures change.

Just because a species goes extinct does not mean that that species was not "fit for survival" at all. It simply means that the species was not fit for survival given the pressures and stimuli of the time they went extinct.

The only measuring stick that matters to evolution is procreation, you're right about that. The part people forget is everything else that happens is just rolls of the dice with no specific desired outcome. If it helps the species survive the current pressures, the trait remains. If not, it either dies out or falls recessive within the species gene pool.

Re:Er.

[Adambomb]

Where did I assume that? What i'm saying is there IS no way to define a peak, since its variable dependant on the time frame and environmental pressures as to what is considered "optimal".

Re:Er.

[someone1234]

PNA might function better than DNA/RNA, but its cost (resources, time to create) is higher and couldn't be afforded by the first organisms.

By your logic humans who wouldn't survive a nuclear war are less efficient than roaches that would survive it.
Just, roaches will never start a nuclear war in the first place.

Re:Er.

[BytePusher]

"A synthetic molecule called peptide nucleic acid (PNA) combines the information-storage properties of DNA with the chemical stability of a proteinlike backbone."

I see two possible reasons PNA was not selected.

First, as others have said, it's stable. Evolution requires a bit of mutation to move forward. Out of a billion mistakes, maybe 1(or less) will cause an organism to be more 'fit.' So, you have a balancing act between errors and fitness, where too many errors reduce an organisms fitness and two few reduce it's adaptability.

Second, the protien backbone is possibly biologically expensive. There are many who believe advances in human intellegence is linked very closely with the availability of massive amounts of protein provided by cooking our food. So, the availability and neccesity of protein could be limiting factors in evolution. So any process which provides the same function with significantly less biological cost, even if slightly inferior in other ways, may be selected.

Re:Er.

[mikiN]

Which is better (from a selfish point of view)?

If your goal is to get off this rock quick, why wait until you've evolved and amassed enough science and tech to go into space (tanking the economy in the process) when you can just hitch a ride?

Earth-born bacteria that hitchhiked along with Mars rovers Spirit and Opportunity possibly are now living on Mars. We (humans) are not.

Re:Er.

[tsa]

So why not dump a whole lot of this newfangled triple helix stuff in the environment and wait a few billion years? Let's see who's the winner then! Will it be DNA or PNA? SMS your prediction to 999-HELIX and win a spaceship!

Re:Er.

[Kagura]

If it helps the species survive the current pressures, the trait remains.

Oops! You mean, "If it doesn't hurt the species' survival under the current pressures, the trait remains."

Re:Er.

[CoderBob]

Except there are plenty of vegan foods that contain protein.

Here's the first google result for searching "vegan protein":

http://www.vrg.org/nutrition/protein.htm

Also, IANAV, but I did know that meat was not the only source of protein.

Re:Er.

[Anonymous Coward]

I completely agree that evolution doesn't mean 'progress' or things getting 'better'. Nevertheless, there unarguably has been a trend in the direction of more COMPLEX life forms over the entire period of evolution of life on earth. Not saying that More Complex means Better. However, More Complex generally suggests More Sophisticated, which, in the popular imagination at least, is perceived as 'better'.

Re:Er.

[Golddess]

Not quite true. It could be that it doesn't hurt it, but doesn't help it either, in which case there are no pressures for or against that trait, so it may or may not remain.

Good

[damnfuct]

I don't care if people build bio-"machines" out of components that are similar to ours. My objection, though, is if they *DO* use the same components as what we are made of. We have no idea how these "parts" would interact with our own physiology, so best that we aim for systems that use as little as possible from our own systems. Using something that is similar but is based in a different manner is good!

Re:Good

[Anonymous Coward]

Yeah sugar-phosphate is just too scary. Lets create life based on stuff we aren't made of like lead and mercury.

Triple helix... finally

[Junior J. Junior III]

This will be how science finally gets us to 6-asses. I am pre-ordering my 6-assed monkey right now.

But will this really be an improvement? I don't even want to think about how many razor blades will be needed to shave all those asses. They'll probably have to come out with a 12-bladed disposable razor or something...

Binding Affinity

[Cinnamon Whirl]

Several years ago, I worked as a chemist for a small biochemical company in the UK, making modified olignucleotides and PNA.
IIRC, PNA had one outstanding feature: It binds to a complementary DNA strand much stronger than DNA itself (due in part to the lack of repulsion in the protein backbone. DNA's phosphate backbone is negatively charged).
Sadly, this means that two stands of PNA will bind extremely strongly to each other, and the forces required to unpair (part of the replication process) them would require different, "stronger" enzymes - so no chance of cell division, and no chance of life. (Still sounds cool though!)

Re:Binding Affinity

[DarkOx]

I don't have much of a biology background but what you say makes sense. If the chemical bonds are stronger in PNA then you have to have other higher energy state free radicals floating about to break them apart which would likely be ractive with other chemical structures in cells that are not reactive chemically with the enzymes that unzip DNA. You might have a more stable "code of life" with PNA but It might not lend itself to the complexities of a eukarotic cell.

Re:Binding Affinity

[spud603]

Out of curiosity, does that make PNA kind of dangerous in quantity for all of us DNA-based lifeforms?
That is, do DNA-based cells exposed to PNA stop being able to reproduce themselves? (DNA unzips, PNA wiggles in and binds, everything shuts down)

Re:Binding Affinity

[wormBait]

Chances are that the PNA would only bind if there was a match in sequence (just like DNA only binds to complementary sequence). However, if it did bind, it would probably get stuck there and thus be effectively toxic. Nevertheless, large molecules like PNAs would be very difficult to get into a cell and would most likely be less toxic than a myriad of other well-known DNA-binders that are very toxic (eg, ethidium bromide).

Re:Binding Affinity

[xZgf6xHx2uhoAj9D]

The problem with storing in DNA (or other biological molecules) is that none of your memory is addressable. There are tricks you can use (e.g., enzymes) that will help you fish out DNA strands of a particular length, or containing a particular sequence as a subword, etc. Essentially the data itself would have to carry some address information in it (i.e., it would have to know how to be found).

Re:Binding Affinity

[Belial6]

Isn't this how all data sent across the internet works? We would just have to store the data in memory the way that we send data across the internet. In packets with self identifying markers.

PNA Too stable?

[crow]

Perhaps PNA is too stable, so that life forms based on it couldn't evolve through mutations quickly enough to adapt to changes.

Re:PNA Too stable?

[Futile Rhetoric]

An excellent point; possibly the same reason why we're stuck with bodies which break down far too quickly -- an immortal organism simply wouldn't evolve.

Re:PNA Too stable?

[spud603]

Heh, good point. The immortal 'species' are still stuck in the self-reproducing-chemical-chains-in-a-pool-of-hot-mud phase...

Re:PNA Too stable?

[Omestes]

Freddy Mercury?

Re:PNA Too stable?

[matt4077]

Unlikely... Given the hoops the cell jumps through to keep DNA somewhat stable, it would have to be quite a few orders of magnitude more stable to be below the current rate of mutations that survive the different repair mechanisms.

Re:PNA Too stable?

[Jorophose]

Nwabudike Morgan?

(but even 500 years would be nice)

Re:PNA Too stable?

[pseudopawn]

So lets just put the DNA source code into the PNA compiler. I'm more concerned about living forever than the future evolution of the species.

Wasn't this part of a movie plot?

[fortapocalypse]

In the beginning of The Fifth Element, Leeloo was created from triple-helix-structured nucleic acids. So does this mean the scientists are just trying to create a punk-haired girl? Typical.

Re:Wasn't this part of a movie plot?

[game kid]

They want to make a redheaded punk-haired girl, so it's a noble cause. ;)

Re:Wasn't this part of a movie plot?

[jackchance]

If they make woman that look like Milla Jovovich, I'm all for it.

Threshold protocol activated

[Lars T.]

nt

Also

[MoellerPlesset2]

There's no such thing as a universal 'better'. What's better has all to do with circumstances, environment - It's the driving force of evolution.
So what's 'better' about PNR? Well, what immediately springs to mind is that it'd be similar to amino acids. And for life, amino acids and proteins are necessary. PNR could be considered 'more primitive' in the sense that it'd be more minimal - it could reuse a lot of the chemical pathways that would need to exist for amino acids.

What's 'worse' about it? I don't know. One likely reason that comes to mind is that it may not be stable enough for long chains, and hence, more complex life. That's the case for RNA. And the RNA-to-DNA transition in nature wasn't an easy one for sure: It's an very energy-demanding reaction that requires radical-formation. (in fact, chemists didn't even think radical reactions occured in biological systems until a decade or two ago)

But was it ever there?

[pentalive]

The big if in your statement is "If PND had existed" perhaps it never expressed in any species and so was never around to compete.

Re:But was it ever there?

[MightyMartian]

I can conceive of a situation where such a molecule might actually be selected against. If the molecule were "too" stable and inhibited molecular evolution, it's quite possible that early life with essentially a "broken" system like RNA, which made events like transcription errors and insertions more likely, then it's quite possible that RNA could have won out over the technically "better" molecule simply out-evolving it.

Re:But was it ever there?

[smellsofbikes]

This could happen right now -- the AIDS virus has crappy reproductive fidelity. Reverse transcriptase does a lousy job of transcribing RNA to DNA so the offspring have lots of mistakes. It has a very much higher rate of mutation, as a result, than DNA transcription enzymes. So what you see is that DNA-based lifeforms evolve very slowly, and AIDS evolves very rapidly. If it managed to kill off all us humans you could (if you weren't dead) make the case that RNA is "better than" DNA because we all died.

There's a balance point for information stored genetically. If you store a lot of information, you can handle more situations, but reproduce more slowly because your cells take longer to divide. If you pare down your genetics to the bare minimum you are very specialized and do extremely well in precisely one environment, and get outcompeted in any other. Likewise, if you have high-fidelity genetic reproduction, a group of animals with that ancestry will continue to do very well in a fixed environment, but if the environment is changing a lot, lower-fidelity genetic reproduction allows for faster adaption at the cost of individual success, because the vast majority of mutations will be detrimental or deadly to the individuals. But as a group, they'll do better. That's what the AIDS virus does: as a group, they evade our immune system, even though individually they die in large numbers.