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Central Dogma of Genetics May Not Be So Central
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."
So you're saying our RNA needs a spellchecker?
Genetic copying is not always perfect! Many researchers are left baffled, having only discovered this themselves several decades ago. Film at 11.
I am scientifically inaccurate.
Who do you think they are, Soulskill, NERV?
Also, science holds no dogma. If it does, it ceases to be science.
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.
It's a small world and it smells funny; I'd buy another if it wasn't for the money; Take back what I paid (SoM)
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.
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.
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.
The good and new comes from no quarter where it is looked for, and is always something different from what is expected.
News for nerds who never took a biology course and are deeply suspicious of the so-called "sciences"
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.
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.
"It is a good thing for an uneducated man to read books of quotations..." -Winston Churchill
(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.
Faster! Faster! Faster would be better!
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...
Laters Sol "Have you found the secrets of the universe? Asked Zebade "I'm sure I left them here somewhere"
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!
The central dogma of genetics is... you don't talk about the central dogma of genetics.
RTFA. These are not errors. They happen the same way in every strand of RNA.
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.
SSC
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,
My webcomic
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
The 'dogma' concerns the direction of information flow (DNA <-> RNA -> proteins), not about how perfect it is.
Thank you, Captain Obvious!
You think? How do you spell mutation?
I'm a BBS orphan in a blogging world.
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.
Everybody gets what the majority deserves.
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.
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.
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 .
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
Wake up to the new world, friends, Ascension has begun. Soon, the humanity will realize that reality is nothing but a shared dream.
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.
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:
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!
RNA actually IS a copy of the DNA. The apparent misspellings are the genetic equivalent of backslash-escaped backslashes and other meta-characters. :)
In which geotrope was the female chromosome unchanged?
The article does suggest that the mistakes are not random. First thing that crosses my mind is can we have a mutation in RNA that will lead to a disease, although the DNA is wild type normal. I know examples where mutations in RNA lead to splicing errors producing the truncated protein, but what Li describes seems to be quite common phenomenon. Second thing is, were all these mistakes in mRNA or non-coding RNA?
Please read the paper's abstract. The ScienceNews article may be complete garbage, but the researchers:
-Are investigating post-transcriptional modification of RNA, not "mistakes"
-Wanted to methodically analyze RNA editing, since our understanding is limited. This was a study to contribute to the understanding of RNA modification mechanisms, not overturn the central dogma
-Someone here mentioned that we already know about A to I conversions in RNA. The abstract mentions these; they're not stupid/unaware- they are trying to find other conversions, and understand _where_ A to I and other modifications occur (where they always occur -> why do they occur at these sites/sequences of RNA)
Please mod this up so that more people read the abstract.
Typically, DNA is thought to be transcribed into RNA in an exact copy of the DNA minus random errors that occur due to poor fidelity of the polymerase that makes it. However, it's been well known for more than 10 years that RNA can be altered systematically through (still mostly mysterious) mechanisms called RNA editing. This is a well known phenomenon that is pretty much universally believed by all biologists. However, RNA editing was thought to be a mostly rare process that only affected a handful of genes. This group used new technology called deep sequencing that allows for high throughput, quantitative sequencing of millions of RNA molecules at once, and their results suggest that RNA editing isn't as rare as once thought. To be fair, this is an abstract submitted to a conference, so it only has undergone the most minimal editorial (not really peer) review based on a paragraph or so of presented data. This may all be an artifact due to some systematic bias of the sequencing platform. There are probably hundreds of other groups using deep sequencing of RNA, so it will be interesting to see if other groups can replicate this.
That mRNAs are edited post-transcriptionally has been known for some time now. In mammals, RNA modifying enzymes will act on specific mRNAs to alter their base structures, thereby changing their amino acid encoding. (too tired right now to provide a link, but this happens for mRNAs coding for AMPA-class glutamate-gated ion channels). It's not so much that it happens per se that is amazing; its that it happens at this large scale.
Much of this stuff is based on nex-gen high throughput sequencing technology, which has emerged just in the past 3-4 years or so. Very cool stuff.
NO CARRIER
The blerb is intentionally misleading etc. We have known for a long long long long long while that there are indeed mutations in cells so not ever fricking set of DNA within your own body is exactly identical. ffs does cancer not ring a bell to anyone?
While it may have been coined as the official term, I've always perceived The Central Dogma as a bit of a tongue in cheek jab at the field of biology. It's an approximation - a substitute - a catchall for as yet unknown processes. An assumption on some level.
One reason a mutation does not necessarily result in an error is the redundancy of the RNA codon. Multiple triplet RNA codes can code for the same amino acid (DNA->RNA->Amino Acid->protein). Some amino acids or coded in 4 unique triplet RNA sequences. So, even if an error is made, the result is often a synonymous mutation - one that codes the same amino acid. So if RNA polymerase picks up an A instead of G at this spot for some reason - it might not matter anyway.
Sadly we scientists are always reinventing the wheel. One lecture in my undergraduate biochemistry class was based entirely on why every assumption in the central dogma was incorrect. Exceptions including RNA changing the expression of DNA, proteins affecting epigenetic changes on DNA, siRNAs and a host of other examples have been long known to science. Scientists keep re-inventing the wheel and journals and editors keep announcing today's latest groundbreaking re-discovery.
Then again.... I'm an idiot.....
...... and idiots rule the world....
I thought that I would say that before some religious nutter makes the claim that ''this shows that Darwin was wrong''.
Can we PLEASE stop referring to parts of the scientific body of knowledge as 'dogma' and 'tenets'? It only fuels the lack of understanding of how science works among non-scientists, giving the creationists (and their anti-science ilk) more fuel for their stupid rhetoric comparing science to religion.
As a sci/tech website, I expect better of /.
You know, since Jack Valenti told us how digital copying is perfect and everything and DNA is digital.
Did you know 80 to 90% of the moderators on slashdot wouldn't recognize a troll even if one dragged them under a bridge.
I can't jump in with an angry post picking abort your posts if you keep acting so reasonable.
Where are the logical fallacy's? where is the unjustified rants?
Sheesh, what has slashdot become?
The Kruger Dunning explains most post on
That's a fail in the interpretation of the article. The central dogma does not guarantee 100% copy. In fact idiopathic diseases (disease of unkown origin) are suspected mis-transcription/translation. None of these processes are perfect. Just because a researcher noticed that it occurs a lot in a white blood cell (which is already known for having regions of hypermutation) might change the prevelance belief, but in no ways alters the central dogma. A lot of work needs to be done in order for the central dogma to be violated. Modified possible, violated, definitely not!
This is not about errors in transcription - it's about a well known process called RNA editing. In fact the DNA is transcribed faithfully, it's just that the RNA bases are modified after the fact, enzymatically. This isn't new - it was found in plants and protists at least 20 years ago. The only new aspect is that the process is much more frequent in humans than previously determined, due to huge amounts of sequence data (both RNA and DNA) that can be generated by next generation sequencing approaches.
The article spoke about RNA editing, that means, things like methylation sites activation or stuff like that... Some errors can be cascading ones if for example a base target for methylation was replaced for by another base during the transcription process, the CpG islands are being prime methylation targets after all...
I'm irritated so many people think they're qualified to comment on this paper. What, because you frequent a technology website and had a college biology course you think your comments on a paper [which you likely didn't even look at] are worth reading? Virtually NONE of these posts are anything more than trash. It saddens me. (I have a MS in molecular biology)