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Central Dogma of Genetics May Not Be So Central

Soulskill posted more than 3 years ago | from the can-we-blame-aol-for-this dept.

Biotech 196

Amorymeltzer writes "RNA molecules aren't always faithful reproductions of the genetic instructions contained within DNA, a new study shows (abstract). The finding seems to violate a tenet of genetics so fundamental that scientists call it the central dogma: DNA letters encode information, and RNA is made in DNA's likeness. The RNA then serves as a template to build proteins. But a study of RNA in white blood cells from 27 different people shows that, on average, each person has nearly 4,000 genes in which the RNA copies contain misspellings not found in DNA."

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196 comments

RNA cure? (0)

Anonymous Coward | more than 3 years ago | (#34168378)

So you're saying our RNA needs a spellchecker?

Re:RNA cure? (0)

Anonymous Coward | more than 3 years ago | (#34168750)

What he's saying is that RNA are like torrents. Sometimes the seeders stop seeding if there aren't enough and your copy has holes it in.

We need to be on alert so the GIIA knows their place.

NEWS FLASH (1, Funny)

millennial (830897) | more than 3 years ago | (#34168382)

Genetic copying is not always perfect! Many researchers are left baffled, having only discovered this themselves several decades ago. Film at 11.

Re:NEWS FLASH (0, Redundant)

Smidge204 (605297) | more than 3 years ago | (#34168396)

Pretty much my reaction. DNA copying is a very high-fidelity but still imperfect process - why would RNA transcription and protein synthesis be any better?

The overall concept is still true.
=Smidge=

Central Dogma Barking Up Wrong Tree (3, Insightful)

ColdWetDog (752185) | more than 3 years ago | (#34168468)

(I so wanted to start the post that way)

No, the big thing about this (if indeed it holds up) is that the fidelity is much, much lower than expected. It doesn't seem that the mRNAs are miscoding (although it's possible) it seems that the coding is being jiggered with by other factors.

However, this is a statistical analysis of a number of genomes and the original genome coding teams warns that the precision of the decode may not be enough to warrant TFA's (tentative) conclusion.

But it's interesting and exciting. Stay tuned. Beats politics.

Re:Central Dogma Barking Up Wrong Tree (3, Insightful)

afidel (530433) | more than 3 years ago | (#34168834)

It doesn't really matter though does it, as long as the transcription errors don't produce toxic analogs of the protein that's being encoded then the body just produces more copies of the protein until it has enough working copies. Yes, it has to expend more energy on creating and destroying the transcription errors but I would venture that this is already accounted for in the cells energy intake since it's probably been with us for a very, very long time =)

Re:Central Dogma Barking Up Wrong Tree (2, Interesting)

ColdWetDog (752185) | more than 3 years ago | (#34169222)

Well the big deal is that they 'errors' are not simple transcription errors (at least that's one way to view the data). Something else is mucking with the transcript that, according to the 'Central Dogma' shouldn't be there.

And yes, the old Central Dogma is getting a bit frayed at the edges given all the newfangled RNAs they seem to discover monthly. That's the fun part.

Re:Central Dogma Barking Up Wrong Tree (0)

Anonymous Coward | more than 3 years ago | (#34168992)

Beats politics.

Yeah, even the tea baggers are discussing RNA sequencing their town hall meetings now. But all they chant is, "It's God's will"...

Re:NEWS FLASH (1)

jd (1658) | more than 3 years ago | (#34168428)

You've got to bear in mind that researchers have only limited memory. They can't afford the 512Mb brain upgrade with all the funding cuts.

Re:NEWS FLASH (0, Troll)

MightyMartian (840721) | more than 3 years ago | (#34168444)

No fucking kidding. That's two articles here in a single 24 hour period making moronic claims (the other being "We reproduced the Big Bang")

I think every journalist who wants to get into science reporting should have be forced to take a six month course to get them up to speed on current understandings in major fields (and by that, I mean, an understanding of what's happened in the last thirty to forty fucking years).

That RNA transcription doesn't always work might have been news half a century ago, but not since then. In other words, the journalist in question is either dishonest or a fucking retard, but in either case should be forced to dig ditches or test industrial chemicals' effects on digestion or something else that has nothing to do with writing.

For the record, all you fucking morons, no genetic process, whether at cell division, transcription or whatever is perfect. This has been known for literally decades. There is absolute nothing here to report.

Re:NEWS FLASH (5, Insightful)

canajin56 (660655) | more than 3 years ago | (#34168560)

Yes, just random mistakes is why 10,000 "accidents" happen to the same exact gene exactly the same way in exactly the same spot every time, 100% of the time, in every cell their bodies, for multiple individuals. Random transcription error. Yes, you sure thought that one through. How embarrassing. No, but seriously, too bad you weren't on the peer review for the paper. You could have saved them from publishing such garbage!

Re:NEWS FLASH (2)

MichaelKristopeit140 (1934372) | more than 3 years ago | (#34169156)

slashdot is no longer a site that can be trusted or expected to link to valid science journalism... instead it is infested by marketeering spinsters pushing their agendas.

slashdot = stagnated

RTFA, the errors weren't random. (3, Informative)

mosb1000 (710161) | more than 3 years ago | (#34168480)

The amazing thing is not that there are mistakes, but the exact same mistakes occur in (almost) every strand of RNA! They aren't random errors, they occur the same way every time!

Re:RTFA, the errors weren't random. (3, Insightful)

PCM2 (4486) | more than 3 years ago | (#34168614)

That's kind of interesting, but not really amazing. Something must be causing the "mistakes" no matter how "random" they appear to be -- whether it's a virus, a stray cosmic ray or something else. The fact that it seems much less random than you'd expect just points to the likelihood that we'll soon get to the bottom of the phenomenon.

Re:RTFA, the errors weren't random. (0)

Anonymous Coward | more than 3 years ago | (#34168810)

This consistent "something" we are speaking of---I got it! That's the "invisible hand" of Libertarianism I always keep hearing about, right? Consistently correcting all of our social, err, genetic problems via free trade, err, wacky tRNA? ;)
-os

Re:RTFA, the errors weren't random. (1)

MichaelKristopeit162 (1934888) | more than 3 years ago | (#34169198)

i don't think you know what libertarianism or free market economics are, and that the people you're listening to are complete morons.

Re:RTFA, the errors weren't random. (1)

Artifakt (700173) | more than 3 years ago | (#34169100)

If strikes by 'stray' cosmic rays are a non-random phenominon, then you've just proved an intelligent super-powerful being deliberately interferes in evolution. I'm glad you think that wouldn't be amazing. Personally, if I'd just proved that, I wouldn't be so blasé. In fact, I'd be demanding the Nobel committee make me Pope and the Roman Catholic church give me a big gold prize, and probably hinting that Ms. Portman should climb out of those grits, towel herself off, and bear my children to get in good with the Shaper of our Genetic Destinies, while I was at it.
        Just out of curiosity, what would you find amazing? I take it the new TV season isn't even in the running?

Re:RTFA, the errors weren't random. (3, Funny)

PCM2 (4486) | more than 3 years ago | (#34169438)

If strikes by 'stray' cosmic rays are a non-random phenominon, then you've just proved an intelligent super-powerful being deliberately interferes in evolution.

True, and if cosmic rays are green, then I've just proven that breakfast cereal is made of oats.

Or to put it another way: If a cosmic ray could strike an RNA molecule and sometimes it would cause a change in the molecule and sometimes it wouldn't, and no observable phenomenon could be used to determine when it would and when it wouldn't, then that would appear to be a random phenomenon. If every single time a cosmic ray strikes the molecule it causes a change, then that is a non-random, cause and effect phenomenon.

Maybe you should have stayed in bed this morning.

Re:RTFA, the errors weren't random. (1)

MichaelKristopeit161 (1934886) | more than 3 years ago | (#34169180)

why would you quote the word "mistakes" implying that they aren't mistakes, yet in doing so, continue to push the terminology you understand to be incorrect?

they aren't mistakes. the replication process is obviously dynamic based on other factors.

Re:RTFA, the errors weren't random. (2, Interesting)

PCM2 (4486) | more than 3 years ago | (#34169398)

I quoted the word mistakes because I don't believe they are mistakes, just like you say. You're chasing your own tail on this one.

Re:RTFA, the errors weren't random. (1)

MichaelKristopeit126 (1933786) | more than 3 years ago | (#34169498)

actually i'm attempting to stop the ignorance you feel justified in propagating.

if they aren't mistakes DON'T CALL THEM "MISTAKES".

you're a "moron"... but i don't mean you're a moron, so don't feel insulted, "moron".

Re:RTFA, the errors weren't random. (0)

millennial (830897) | more than 3 years ago | (#34168664)

I didn't say the errors were random, now did I? I said the copying wasn't always perfect. Consistently incorrect copying is not perfect.

Re:RTFA, the errors weren't random. (1)

mr_mischief (456295) | more than 3 years ago | (#34169056)

Consistently incomplete doesn't necessarily mean consistently incorrect. Maybe you'd really rather certain portions of the DNA are reliably not transcribed to matching RNA.

Re:RTFA, the errors weren't random. (1)

hajus (990255) | more than 3 years ago | (#34169260)

That's kinda like comment lines reliably not making it to the machine code.

Re:RTFA, the errors weren't random. (4, Informative)

SETIGuy (33768) | more than 3 years ago | (#34168754)

Even that's not amazing. It would be amazing if it made a different mistake every time.

The simple model of transcription had always been that single nucleotides in DNA are matched to the complementary nucleotide on the RNA strand. But, of course, nobody thought the simple model was always correct. You've got the interaction of a DNA strand trying to fold back on itself and an RNA strand trying to fold back on itself, and a big honking RNA polymerase molecule with an extremely complicated electric field. It's to complicated for the simple model to work. Maybe on occasion the order of the codons a few hundred bases from the transcription site will interact with the RNA polymerase to insert a different base than expected. (Just throwing that out as a possibility. It could be any of a million things, like an induced change in the structure of RNA polymerase.) That's fine, as long as it happens the same way every time. In that case it's not an error in the DNA or the RNA. It's an error in our oversimplified model of how RNA transcription works. So now we need a better model that can predict how a DNA sequence will be transcrived. Don't look now, science is working the way it should!

I hate that they are even using the word dogma. Because actually dogma is never based on or swayed by evidence. And in this case the dogma was "it's simpler than any realistic biochemical system." I'd like to see a poll of how many biochemist, molecular geneticists, virologists and microbiologists actually believed this dogma.

Re:NEWS FLASH (1)

interkin3tic (1469267) | more than 3 years ago | (#34168920)

As others have noted, it's apparently not random, but bigger exceptions to the central dogma have been known for decades. I was thinking that the whole title of "central dogma" was an ironic title that we've played up more (though I have no idea the history of the term.) Retroviruses were a huge violation of the rules, going from RNA into DNA. It seems to me like micro RNAs regulating translation of mRNA into protein diddles the rules a bit as well. The "dogma" as described here ("DNA letters encode information, and RNA is made in DNA's likeness. The RNA then serves as a template to build proteins") also seems to be shot to hell with RNA splicing, introns are cut out of the message, often in a variety of different patterns.

Proclaiming that central dogma has been broken seems a bit like saying we discovered a new land called "America" yesterday. The actual abstract makes no such headline grabbing claims.

nothing to do with copying fidelity (0)

Anonymous Coward | more than 3 years ago | (#34168986)

This has nothing whatsoever to do with the accuracy of copying DNA into RNA

It has to do with a process that has been know for some time - after the RNA copy is made, the cell has machinery (enzymes) that change part of the RNA sequence

What is new about this work is that this phenomenon appears to be much more widespread then thought .

Central Dogma? (2, Insightful)

Microlith (54737) | more than 3 years ago | (#34168384)

Who do you think they are, Soulskill, NERV?

Also, science holds no dogma. If it does, it ceases to be science.

Re:Central Dogma? (2, Funny)

digitig (1056110) | more than 3 years ago | (#34168582)

Also, science holds no dogma.

Is that a dogma that science holds?

Re:Central Dogma? (0)

Anonymous Coward | more than 3 years ago | (#34169216)

CARPE DOGMA!

Re:Central Dogma? (0)

Anonymous Coward | more than 3 years ago | (#34169622)

Also, science holds no dogma.

Is that a dogma that science holds?

This article is a blatant overstatement of the actual study's findings. RNA editing was a concept already known and considered relatively prevalent. This study simply identifies additional sites at which the editing takes place, previously unknown. It's an important and interesting finding, but by no means unearthing the Central Dogma of molecular biology. Not even close.

Re:Central Dogma? (4, Interesting)

mauthbaux (652274) | more than 3 years ago | (#34168584)

Actually, as I was taught it (which, I will readily admit, could be wrong), Central Dogma is in fact the proper term, though the definition has been tweaked over time.
Originally it stated something along the lines of, One DNA gene is transcribed into one RNA transcript, which is then translated into one protein.
The discovery of antibodies threw that concept out the window. Variability in intron splicing and recombination means that a small handful of genes can yield a huge variety of protein products (See VDJ recombination).
Yet another twist was added with the discovery of retroviruses which reverse the direction of transcription, turning RNA into DNA. Previously we had thought the central dogma to be unidirectional.
The more we learn about life's mechanisms, the less surprised we are when exceptions to the rules are discovered. Evolution really is the ultimate hacker; constantly expanding the usefulness of very simple resources.

Also, kudos on the evangelion reference.

Re:Central Dogma? (2, Informative)

jd (1658) | more than 3 years ago | (#34168798)

There are many, many twists to this sordid puzzle, but you are correct. The concept of a 1:1:1 translation has been dead for a very long time.

Re:Central Dogma? (3, Funny)

Bigjeff5 (1143585) | more than 3 years ago | (#34168840)

The use of the term "dogma" in "Central Dogma" was incorrect from the get-go. Frankly, Francis Crick either chose to misunderstand the word or simply didn't fully grasp its connotations.

He was just looking for a more dramatic word for "hypothesis".

"Central Hypothesis" would be the more accurate name for it. It isn't a proper theory, but it does provide a framework for understanding molecular biological functions.

It's basically this (from WP): 'once information gets into protein, it can't flow back to nucleic acid.'

Re:Central Dogma? (2, Interesting)

interkin3tic (1469267) | more than 3 years ago | (#34169024)

Scientists sometimes use "dogma" in a sarcastic manner. As others have pointed out, this dogma is not so much a "universal rule" as it is "a general guideline with more exceptions than you can shake a stick at."

Stephen Jay Gould talked about the dogma of gradualism. To hear him tell it, evolutionary biologists were telling the fossils that, no, they couldn't possibly be identical to their ancestors from hundreds of thousands of years prior, they had to have made some mistake in where their bones became buried, that this mollusk in sediment ten million years old was the same age as this mollusk in sediment that was 9 million years old, because they were too similar looking and didn't show gradual signs of evolving. Now the currently held theory is that evolution happens rapidly at the beginning of a specie's existence and then they don't change for very long periods of time. I suspect that the evolutionary biologists who were gradualists wouldn't have defended their views as dogma.

Similarly, creationists are always trying to call evolutionary theory a dogma and say it's more religion than science, the scientists themselves laugh at that suggestion (or consider moving to another country.)

Anyway, yes, dogma is not a commonly used term to describe one's own scientific views, and every time I've heard of the "central dogma of molecular biology" it's been followed by examples of how that dogma is wrong in many cases. I'm wondering if anyone ever used that term before those exceptions were found.

Why is this news? (4, Informative)

jd (1658) | more than 3 years ago | (#34168412)

We have known for many years that the same DNA codes to different proteins, with the adjustments given the information in the non-coding regions AND the information in the epigenome. That people have discovered that the intermediate step is also adjusted can hardly be called a shock. The proteins have to get built differently somehow, so some alteration in the intermediate coding was inevitable. Honestly! If geneticists aren't even reading their own bloody papers, maybe the government grants should be issued to those Slashdot readers who do.

Re:Why is this news? (4, Funny)

Fluffeh (1273756) | more than 3 years ago | (#34168442)

Honestly! If geneticists aren't even reading their own bloody papers, maybe the government grants should be issued to those Slashdot readers who do.

Tell us how you feel. Don't hold anything back. You are in a SAFE environment here... Now, show me on the dolly where the geneticist touched you...

Side note: Totally agree with the comment :)

Re:Why is this news? (1)

noidentity (188756) | more than 3 years ago | (#34169054)

Tell us how you feel. Don't hold anything back. You are in a SAFE environment here... Now, show me on the dolly where the geneticist touched you...

I think you mean, show me on the memory map where the program inappropriately accessed memory.

Re:Why is this news? (4, Insightful)

RobinEggs (1453925) | more than 3 years ago | (#34168492)

That people have discovered that the intermediate step is also adjusted can hardly be called a shock.

Yes, it is a shock. The prevailing thought was that the RNA was transcribed faithfully and then that perfect transcript of the DNA was sliced up in strange ways. These people have discovered that the transcript may never have been perfect at all.

Imagine cutting up a loaf of bread: The geneticists were quibbling about how thick the slices were and how to arrange it on the plate, all without paying attention to what kind of bread they used. Now suddenly they've noticed that the recipe for french bread gave them a sourdough loaf while they aren't looking, and it may not be about the slicing as much as about how the right recipe is giving them the wrong thing to cut up.

Re:Why is this news? (1)

MightyMartian (840721) | more than 3 years ago | (#34168522)

Who thought it was perfect? The only people that thought that, I suppose, were high school students receiving a highly idealized version of cellular protein synthesis (sort of like perfect gasses, etc.) No researchers ever thought it was perfect, because it would be all but impossible to create such a perfect system. If there's any revelation here, it's that protein production is more error tolerant than we once thought, but no one since the discovery of DNA/RNA has ever thought that the system was perfect or even near-perfect. Providing, overall, the transcription produces the "coded" proteins well enough, there will always be a margin of error, whether high or low (and I'm assuming, considering we're talking about RNA, that that margin of error would be considered moderate).

Re:Why is this news? (2, Interesting)

ColdWetDog (752185) | more than 3 years ago | (#34168558)

NOBODY THOUGHT IT WAS PERFECT

The weird thing (from TFA) is that the imperfections aren't we're they're 'supposed' to be.And there are too many of them.

Robin Egg's analogy is pretty good. Let me try a car analogy: You're in a BMW factory, on the input side, all the instructions and parts are geared towards making BMWs - maybe different colors, different hood ornaments or whatever.

Out pop some BMW's as expected. And a couple of Yugos.

Well, no, that's not right. Go with the baking analogy.

Re:Why is this news? (0)

Anonymous Coward | more than 3 years ago | (#34168784)

As a scientist, in genomics, this was a huge surprise to me.

We know from sequencing the genomes that changes in DNA are very rare.
DNA to DNA duplication is a high fidelity process.

We can copy DNA in tubes with great success. Errors are exceedingly rare, even without correction.

To find that some genes are always mistranscribed changes how we thing about genes.
These are NOT errors, they are reproducible artifacts from an unfamiliar process.

Re:Why is this news? (1)

ColdWetDog (752185) | more than 3 years ago | (#34169236)

That's right. It's funny, most of the posters (who don't appear to be of the biological persuasion) really aren't getting this.

I'm gonna have to work on the car analogy a bit longer.

Re:Why is this news? (2, Interesting)

Artifakt (700173) | more than 3 years ago | (#34169324)

Exactly - there's a difference between getting an occasionally screwed up BMW, with a random seeming defect, and getting an occasional Yugo, or maybe a working Jetpack, or every time the BMW is not to spec it's always because it has only four lug nut shafts on the left rear wheel, and the spacing also adjusts to make them symmetrically placed, rather than you seeing a host of other defects that are theoretically as likely. Or maybe it's something that definitely won't work as well, definitely what would be called a damaged product, but still it's still a very common glitch compared to the predicted likelyhood, and it's strange a bunch of other glitches aren't also more likely.
      What I like about this discovery is it's stranger than it sounds in summary to most of the lay public on Slashdot - that's a good sign. It means instead of there being a 1 in 10,000 chance it's really significant research, the odds are more like 1 in 100. There's still a good chance it will end up being no big deal, but it just might.

Re:Why is this news? (4, Interesting)

jd (1658) | more than 3 years ago | (#34168738)

Well, no. The transcription cannot be faithful because there are more letters in RNA than in DNA. Even if you ignore that aspect, geneticists knew that there was a data-driven transform somewhere. Assuming that it is in point A rather than looking is not the hallmark of a scientist. That is the hallmark of the incompetent. Never, ever extrapolate further than the data will permit on the assumption that the extrapolation is valid. Extrapolation should only ever be done for the purpose of creating a hypothesis. Leave articles of faith to religion. On second thoughts, the religious tend to extrapolate beyond limits too, so that might not help.

Anyways, the fact is that there are only two possible places in which a transform could happen (and it could happen in both). This gives you a total of three possibilities. Now, only the DNA-to-RNA step could include information from the non-coding regions. It's possible that either stage could be effected by the epigenome. From this, it follows that two of the three cases involve the DNA-to-RNA step and two of the three methods involve the DNA-to-RNA step. It may be unexpected, in that they may not have considered that possibility sufficiently, but to call it a shock implies that they ignored the mechanisms entirely -- mechanisms the genetic scientists have been studying in depth for a very long time.

Re:Why is this news? (0)

Anonymous Coward | more than 3 years ago | (#34169034)

the abstract says nothing of the sort.

"we showed that RNA editing is very common in humans and the editing sites are not confined to those carried out by ADAR (A-to-I) and APOBEC (C-to-U)."

The paper researches POST-transcriptional modification, not co-transcriptional modification. The only shock that this paper presents is that post-transcriptional RNA editing is more common than previously hypothesized..

Re:Why is this news? (1)

mosb1000 (710161) | more than 3 years ago | (#34168508)

Just because other research indicated this might be the case doesn't mean that this was previously known. Do you really think it unnecessary to actually determine if your assumptions are correct? I hope you aren't using and government grant money.

Re:Why is this news? (2, Interesting)

jd (1658) | more than 3 years ago | (#34168638)

There are four letters in DNA, five letters in RNA. That tells me that something about not copying identically was indeed previously known. The protein encoding was also known for a fact - it wasn't just indicated, it was pretty much accepted by the genetics community as having been sufficiently gone over to be considered standard fare.

The question was WHERE the change happened - DNA to RNA, or RNA to protein? That wasn't established. Two possibilities, one (or both) could be possible. That gives two out of three outcomes in which the DNA to RNA conversion is not a carbon-copy but data-driven. Forgive me for being cynical, but finding out that an event with 2/3rds odds of happening actually happening is hardly "shocking". It might be interesting, it might be informative, it might be many things. But to call it "shocking" is absolutely insane.

Re:Why is this news? (1)

Artifakt (700173) | more than 3 years ago | (#34169500)

The four bases in DNA aren't the same as codons in the code - there are 64 codons set up as triplets of bases in DNA, even though of those, 61 are used to code for only 20 amino acids and the remaining 3 code for a STOP bit. Messenger RNA uses the same number of codons by the model, including also having three ways to express a STOP. There are some already known exceptions, mostly some uncommon organisms use one or two of the three STOP bits to code for an amino acid instead. Incidentally, the START bit (AUG) is also used to code an amino acid (methionine) when the process of transcription is already running - economical, that. Another thing already known is that some choices for coding the same amino acid are much more common than others. That fact suggests there is more to the code than this model and there's something, (perhaps even a whole 'nother level of interpretation) we don't have a grip on yet, but some researchers think it may alternately be explained just as a consequence of some triplets having higher energy requirements to make than others.

Re:Why is this news? (1)

wizardforce (1005805) | more than 3 years ago | (#34168592)

This is the important part of the article, everything else is comparatively irrelevant:

The researchers don’t yet know how the RNA misspellings happen. They could be substitutions made while the RNA copy is being made, or the changes could happen later. The consequences of the misspellings are also unknown.

Not knowing why this is occurring so frequently is what is truly interesting about this, at least from my point of view as a biochemist.

Re:Why is this news? (2, Insightful)

jd (1658) | more than 3 years ago | (#34168782)

Now that is very different. Not knowing why is indeed very interesting. The consequence of the misspellings depends on whether they ARE true misspellings versus data-driven modifications from non-encoding genetic material. If they are deliberate transforms, then to call them misspellings is flawed, since the spelling would then be precisely what the DNA coded for (when considering all other types of data). Likewise, when U is used in RNA, it is not considered a mis-spelling, even though that would not be the nucleotide in the DNA.

Now, there may well be consequences for non-encoded mis-spellings, and the consequences of those would be extremely interesting.

This, really, is where the interest should be.

Re:Why is this news? (2, Informative)

Cockatrice_hunter (1777856) | more than 3 years ago | (#34168932)

I agree that we've always suspected that transcription isn't a high fidelity process. In fact, there is evidence that leads us to this conclusion (ex. the lack of a 'spell-checker' mechanism). However, just because we have evidence that points to an effect doesn't mean that it shouldn't be tested. The thing is, we've been surprised before. We've had evidence of other phenomena/behaviour should exist but when actually tested, it turned out that it was not as expected. For example, in the past it was thought that during ischemic events it was the lack of oxygen and nutrients that did the most damage, now it is known that reperfusion and the immune response subsequent to ischemic injury has a significant role in the damage done. As pointless as some of these experiments must seem, they still have to be run to test the conclusions of those other 'bloody' papers that the geneticists are reading.

On a side note, the genetic code is built in such a way that small errors here and there during the transcription process may not have a huge effect (64 codons represent ~20 amino acids plus a few stop codons).

Re:Why is this news? (1)

Artifakt (700173) | more than 3 years ago | (#34169240)

The problem is, that Natural Selection requires, in theory, that there be some pretty strong limits on blending. The classic Mendelian model implies a code that is pretty reliably non-blending and that in turn is one of the things that makes NS count as science. That is, it had predictive power - Darwin's original work caused him to predict that when the code was discovered, it would allow, at most, only very limited blending. * "One DNA sequence yields one protein, now and forever" also works to make blending rare at best. The more there's something else there, the more the questions that follow can include "Does that something allow more blending than is good for the fundamental dogma of natural selection?" (which is not the same as the 'fundamental dogma of genetics'). Now personally, I doubt that whatever mechanisms we are looking at here have any strong influence on just how much 'blendability' is possible in genetic code transmission, one way or the other. But I wouldn't doubt either that some 'creation science' fan will seize upon this or that some geneticists would get premptive at the very possibility.
      So why is this news? In part because it has an impact on the politicization of science, as well as on the actual science.

* It's amazing - scientists debated for decades whether height was a trait that blended or whether there were several genes controlling height to give a superficial appearance of blending, and so on. It was the 1970's before someone pointed out that Gender itself was a trait that almost never had any intermediate blended expression, even though that fact had been staring geneticists right in the face for about 100 years, since genetics itself began.

RNA is a total slacker (0)

Anonymous Coward | more than 3 years ago | (#34168414)

Why doesn't RNA shape up like good old DNA? DNA's doing all his work, while RNA just dozes off and turns in half-assed work.

This is NOT what the central dogma says (3, Informative)

Anonymous Coward | more than 3 years ago | (#34168420)

What it does in fact say is that information flows from DNA to RNA to proteins, and not the other way around: proteins can't write DNA.

Re:This is NOT what the central dogma says (3, Insightful)

afidel (530433) | more than 3 years ago | (#34168898)

Except for protein encoded viruses of course which rewrite RNA and sometimes DNA =)

Re:This is NOT what the central dogma says (0)

Anonymous Coward | more than 3 years ago | (#34169600)

But they do so from their own nucleic acid sequences, they don't reverse transribe their proteins back to codons.

It's called an "error rate" (4, Informative)

sam_handelman (519767) | more than 3 years ago | (#34168422)

This is not nearly as earth-shattering as the journo makes out.

  When DNA is copied to make new DNA, you get a certain number of copying errors, called mutations - most of them harmless. I assume everyone knows about those.

  When DNA is copied to make a temporary-working-copy RNA, you get a larger number of these copying errors because, in general, they are one-shot non-critical deals. The need for stringency is much lower, the selective advantage for stringency is not so great, so it comes as no surprise that the level of proof-reading is also reduced.

  Now, it's also possible that there are mechanisms by which these RNA molecules can be purposefully edited. As mentioned in the article, significant post-transcriptional editing (including in eukaryotes the readaction of big chunks, which are called "Introns".) But this finding doesn't speak much to that, although the rate is a *sconch* higher than I might expect for random errors. Even so, this doesn't shake the central dogma of molecular biology in any meaningful way, as for example Reverse Transcriptases did.

Not "errors" (1)

mosb1000 (710161) | more than 3 years ago | (#34168526)

RTFA. These are not errors. They happen the same way in every strand of RNA.

Re:Not "errors" (1)

millennial (830897) | more than 3 years ago | (#34168684)

A consistently-made error is still an error. Randomness is not a prerequisite for being called an error.

Re:Not "errors" (1)

Bigjeff5 (1143585) | more than 3 years ago | (#34168860)

If it's consistent, would it not be selected for and therefore not really an error at all?

Once an error becomes fundamental to the system, it's not an error.

Re:Not "errors" (1)

millennial (830897) | more than 3 years ago | (#34168926)

I think we're getting into a disagreement on semantics here. If it's not copied 1:1, it's technically a copying error, even if it's selected for. You may be onto something, though; we thought it was a system for perfect copying, but it's starting to seem like the system wasn't meant for that in the first place. Surprise, surprise: evolution produces another imperfect mechanism.

Re:Not "errors" (1)

sdiz (224607) | more than 3 years ago | (#34169048)

What if we were not "copying"?

When a student plagiarize others' work, he change some bits from the original. Is this an error?

Re:Not "errors" (1)

millennial (830897) | more than 3 years ago | (#34169356)

That's where I think this is leading: an understanding that copying errors may not be errors, but intended results of a process we might not have been totally familiar with before.

Re:Not "errors" (1)

afidel (530433) | more than 3 years ago | (#34168912)

Doesn't mean they aren't errors. Just because a high percentage of people are improperly encoding the RNA for this protein doesn't mean that it's not just a common defect. For all we know this is a defect holdover that at one point conveyed some advantage like sickle cell anemia providing a partial immunity to malaria.

Re:It's called an "error rate" (1)

semiotec (948062) | more than 3 years ago | (#34169616)

Not to mention that a whole bunch of stuff happens between transcription (DNA -> RNA) and translation (RNA -> protein).
The ends have to be capped and modified, in eukaryotes the transcript is only a precursor and has to be spliced into the mature sequence, then the whole thing is exported from the nucleus to the cytoplasm.
Plus there's a whole bunch of stuff happening that we don't really know about, like pseudouridylation and methylation of specific sites.
Not to mention, there's always the good old mutation that occurs. We only know about mutations that get passed on, but these are blood cells (made by bone marrow), not germline cells.

Slashdot (4, Funny)

BitHive (578094) | more than 3 years ago | (#34168426)

News for nerds who never took a biology course and are deeply suspicious of the so-called "sciences"

Re:Slashdot (1)

chebucto (992517) | more than 3 years ago | (#34168506)

News for nerds who never took a biology course and are deeply suspicious of the so-called "sciences"

They didn't even read The Economist [economist.com]. In 2007.

Conservative subs or not? (4, Insightful)

RobinEggs (1453925) | more than 3 years ago | (#34168446)

The summary and the abstract really say almost nothing other than to confirm that the misspellings aren't random and don't seem like lab artifacts.

I'd be interested to know how conservative these mistakes tend to be. If the mistakes generally replace amino acids with very similar ones it might be a programmed method of prodding just how much variation a structure can take while remaining functional. Weird and random events, which can be only so weird and so frequent before everything breaks entirely, are necessary for evolutionary adaptation, and these weird protein errors might be a previously unknown mechanism of exploring slightly different structures for proteins and seeing how far an organism can push the envelope.

No Surprise (2, Insightful)

flyingkillerrobots (1865630) | more than 3 years ago | (#34168448)

Any engineer should find this to be perfectly intuitive. When the DNA itself replicates to produce a new cell entirely, there are a lot of extra safeguards to ensure as near-exact copying as possible, as mutations can easily be fatal. For RNA copying, there is no need for this sort of precision, because even if the resulting protein is useless, the cell remains alive, and a new RNA strand can easily be produced if needed.

Re:No Surprise (1)

MightyMartian (840721) | more than 3 years ago | (#34168482)

Engineers are probably the absolute worst people to be judging complex biological processes like reproduction. In fact, even during meiosis and mitosis, there are all sorts of flaws. It's one of the driving forces of evolution, creating at least a certain fraction (just what that is is still up for debate) of the variation in any population's genome.

Re:No Surprise (0)

Anonymous Coward | more than 3 years ago | (#34168628)

Engineers are probably the absolute worst people to be judging complex biological processes like reproduction.

Ummm, why?

Re:No Surprise (1)

wizardforce (1005805) | more than 3 years ago | (#34168600)

For RNA copying, there is no need for this sort of precision, because even if the resulting protein is useless, the cell remains alive, and a new RNA strand can easily be produced if needed.

The problem with thinking that way is that these "errors" are not random like transcriptual errors usually are.

Mutations (1)

s0litaire (1205168) | more than 3 years ago | (#34168470)

Thought I read somewhere that when the first cells started to form in the primordial soup they were more RNA than DNA since that gave them rapid mutations, the ability to adapt quickly and evolve.

Later on as Cells and organisms became more complex, DNA took over since it was more stable but mutates / evolves at a slower rate...

Re:Mutations (2, Interesting)

MightyMartian (840721) | more than 3 years ago | (#34168544)

It seems likely that the earliest replicators (they may not even have been cells, per se) probably did not use RNA and DNA at all. RNA would have been a somewhat later innovation, like lipids being used to produce simple membranes to create a semi-permeable barrier to protect replication and protein synthesis. At that point we would have had simple cells.

Re:Mutations (3, Informative)

rnaiguy (1304181) | more than 3 years ago | (#34168780)

It's actually believed that the earliest forms of biochemical life consisted almost entirely of RNA. It is the only molecule we know of that can act as both information storage/transport and chemical catalyst (all proteins made by modern life are in fact polymerized by a reaction catalyzed by RNA). There is some disagreement as to whether this "RNA world" came before or after lipid membranes.

Central Dogma (0)

Anonymous Coward | more than 3 years ago | (#34168488)

The central dogma of genetics is... you don't talk about the central dogma of genetics.

Wind DNA gradyooate? (3, Funny)

zach_the_lizard (1317619) | more than 3 years ago | (#34168570)

I for wun du not mind the speling erorz. So long as they kan reed it, wut difurinc duz it maek? Itz not liek thuh bodee iz a speling Notzee.

Thanck God! (3, Funny)

T Murphy (1054674) | more than 3 years ago | (#34168572)

nearly 4,000 genes in which the RNA copies contain misspellings

I new my bad speling wasnt my falt- its just genetic. Finaly I can prove it to my teacher! I hope scientists next fined genes with bad grammar,

Not news. (1, Informative)

pesho (843750) | more than 3 years ago | (#34168596)

How is this news? RNA editing has been known for so long that it is already in the textbooks.

From the article: The most common of the 12 different types of misspellings was when an A in the DNA was changed to G in the RNA. That change accounted for about a third of the misspellings.

This is a textbook example of RNA editing by adenosine deaminase. It will convert the Adenosine bases ('A') to Inosine ('I'). When they try to sequence the RNA the first step is to make a DNA copy. During the process the positions that contain 'I' are copied mostly as 'G'. This is because 'I' can pair with any base, but prefers 'C'. So in the first strand you will get 'C' paired with 'I'. When you build the second strand these 'C' positions will direct incorporation of 'G'.

Mystery solved

Re:Not news. (0)

Anonymous Coward | more than 3 years ago | (#34168828)

I'll be sure to let UPenn and UNC know that you're smarter than their entire biology departments. It may or may not be all that astounding in the long run, but to say it's clearly just a "textbook" case of something patently obvious underestimates the intelligence of many qualified and dedicated people just a little bit, don't you think?

direction of information flow (1)

neonsignal (890658) | more than 3 years ago | (#34168622)

The 'dogma' concerns the direction of information flow (DNA <-> RNA -> proteins), not about how perfect it is.

NO SH*T (0)

Anonymous Coward | more than 3 years ago | (#34168660)

Thank you, Captain Obvious!

More than one way to a result (2, Interesting)

Caerdwyn (829058) | more than 3 years ago | (#34168842)

So here's a question.

Suppose that this "error" that happens every time nonetheless yields the same original DNA sequence?

dna half-strand ACTG ----> rna TATTCGAGATATAC ---> dna half-strand ACTG

It's been a very, very long time since I took my college biology, so be kind if I'm wrong. My point is that these might not be "errors" at all, just alternate intermediate steps that generate the same ultimate results. The assumption to date seems to be "one, and ONLY one, amino acid on RNA yields one, and ONLY one, corresponding amino acid on DNA". Is that necessarily the case, every time? I'm quite sure about ohhhh, a billion molecular biologists have already thought about this. I just don't know the answer.

that word dogma... (1)

hyperion2010 (1587241) | more than 3 years ago | (#34168850)

Should have tipped you off that there were going to be quite a few exceptions. Whether there is 100% fidelity is another question altogether. Furthermore you need to know what portion of those RNA transcripts are actually being translated into protein and whether different variations in sequence are correlated with the relative rate of translation etc.

Yet another of God's screw-ups. (1)

Warwick Allison (209388) | more than 3 years ago | (#34168866)

When I get into Heaven, I'm going to take all this crap straight to top management. Perhaps if He spent less mana on Marketing and more on Product Development, we wouldn't be the quarantined laughing stock of the galaxy. It's so god-damned lonely being a mutant freak.

NO no no, these comments are all wrong (1)

cinnamon colbert (732724) | more than 3 years ago | (#34169074)

The article has nothing to do with how faithfully the DNA is copied; it is about a well known process where a faithfull RNA copy is changed in a specific manner. In any event, the idea of the central dogma has been dead at least since the discovery of retroviruses (early 70s) not to mention splicing (late 70s) I don't know how well the accuracy of making RNA copies (RNA pol II transcription error rate) has been studied (with nods to cairns and starvation induced mutation in the lac system) but the error rate of DNA polymerases varies from ~ 1 in 10^4 for taq during PCR (high error rate) to ~ 1 in 10^8 in vivo in humans (recent paper from sanger on the 1,000 genome project) I would say for humans, in vivo, that DNA polymerase has an error rate of about 1 error in every 10^8 bases copied However, the cell expends a lot of energy on ensuring the fidelity of DNA copying I imagine tht the fidelity of RNA copying is less good, simply cause the effects of an error are much less, so evolution has not selected for stringent copying mechanisms As to scientists not paying attention to published papers - do you have any idea whatsoever how many papers on genetics are published every day ? You would spend all your time just reading the titles, let alone the abstracts

Well, this is it! (0)

Anonymous Coward | more than 3 years ago | (#34169082)

Wake up to the new world, friends, Ascension has begun. Soon, the humanity will realize that reality is nothing but a shared dream.

Not so Surprising... (4, Interesting)

Genda (560240) | more than 3 years ago | (#34169130)

The fact that the "errors" are consistent, suggest this is not an error at all. There was a famous experiment utilizing genetic algorithms to build an optimal circuit with the least possible number of components. It was a simple circuit, and the optimal circuit was well understood. It was an attempt to prove that the genetic methodology would quickly yield this optimal circuit. To everyone's surprise, the process yielded a circuit with fewer parts than the theoretically optimal circuit. What the designers of the experiment hadn't taken into consideration was that the genetic algorithm didn't care about theory, only outcome. It had discovered a heretofore unknown capacitive reactance on the closely spaces lines of the experimental circuit board, and found a way to use that capacitance to reduce the number of parts in it's design. Given the nature of the system, evolution found a clever way to engineer around the believed limitations of the experiment, and utilize any and all real world resources to create a solution transcending of the point of view of the experimenters.

Likewise, there's something interesting going on here with the RNA, well outside of the obvious perspective of the researchers. Bring in biochemists, theoretical physicists, and maybe a couple applied organic chemical engineers. Let them figure out what's happening at the quantum and molecular level to have this outcome be the result. Start doing simulations. Look at topologies and protein folding.

Look at CJD (Creutzfeldt-Jakob Disease) or BSE (Bovine Spongiform Encephalopathy) the causative agent is a prion. A vital protein that in its normal state is essential to neurological function, which can fold in more that one way, and folded the wrong way destroys brain tissue and ultimately causes dementia and death. I'll bet dollars to donuts, that there is some funny quantum state, or a protein folding problem, or some simple nonbiological chemical process whose probable result is a code misspelling in protein formation. Its an interesting problem, but not at all surprising. We are complex systems, and trying to force the world processes that make us possible into a box is at once myopic and foolish.

Re:Not so Surprising... (1)

epifreak (1455095) | more than 3 years ago | (#34169654)

Look at CJD (Creutzfeldt-Jakob Disease) or BSE (Bovine Spongiform Encephalopathy) the causative agent is a prion. A vital protein that in its normal state is essential to neurological function, which can fold in more that one way, and folded the wrong way destroys brain tissue and ultimately causes dementia and death. I'll bet dollars to donuts, that there is some funny quantum state, or a protein folding problem, or some simple nonbiological chemical process whose probable result is a code misspelling in protein formation. Its an interesting problem, but not at all surprising. We are complex systems, and trying to force the world processes that make us possible into a box is at once myopic and foolish.

Species like rabbits are resistant to prion infections and comparison of the crystal structures of prion protein in rabbits and in hamsters reveals why rabbits cannot get infected while hamsters can - its solely a protein folding problem.

For what it's worth.. (0)

Anonymous Coward | more than 3 years ago | (#34169300)

The article is utterly wrong in its references to the central dogma, as are most of the comments here (and most other popular and scientific articles for that matter. Even James Watson in his genetics textbook made the same mistake!).
Please actually read Crick's 1958 paper 'On protein synthesis', but I'll quote the relevant section here:

The Central Dogma
This states that once 'information' has passed into protein it cannot get out again. In more detail, the transfer of information from nucleic acid to nucleic acid, or from nucleic acid to protein may be possible, but transfer from protein to protein, or from protein to nucleic acid is impossible.
Information means here the precise determination of sequence, either of bases in the nucleic acid or of amino acid residues in the protein. This is by no means universally held-Sir Macfarlane Burnet, for example, does not subscribe to it-but many workers now think along these lines. As far as I know it has not been explicitly stated before.

So it is clear from this that Crick is simply stating that once sequence information has been transferred from nucleic acid (either DNA or RNA) into protein, we cannot get the original sequence information back again. This follows from the redundancy in the genetic code and there is to date no evidence to contradict this.
People have been claiming to have refuted the central dogma for decades (retroviruses, alternative splicing, epigenetic modifications, small regulatory RNAs, etc.), when in fact they have simply misstated, misinterpreted or misunderstood (or most likely, never even read) what Crick said.
Crick realized this and wrote a second paper ('The central dogma of molecular biology') in 1970 in which he made his position even clearer, but to no avail. It seems that the popular, incorrect, interpretation of the central dogma is now too well established, even amongst scientists who cite one or both of his papers in their own articles!

The explanation comes from CS. (1)

Kaz Kylheku (1484) | more than 3 years ago | (#34169328)

RNA actually IS a copy of the DNA. The apparent misspellings are the genetic equivalent of backslash-escaped backslashes and other meta-characters. :)

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