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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."
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)
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.
(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!
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!
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!
ASCII stupid question, get a stupid ANSI
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
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.
"Operating systems suck: you're better off using only the BIOS" --trainsaw.com
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.
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.'
Security is mostly a superstition... Avoiding danger is no safer in the long run than outright exposure. - Helen Keller
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.
You are right about the central dogma. It was formulated in 1958 and states that information flows from DNA->RNA->protein. Since that time it has been ammended many times. Just because it is genereally not true, does not mean it is not useful. For example, Newton's mechanics is generally not true, but it is quite usefull for some applications.
Just running some numbers (based on the abstract)
4 x 10^7 reads * 50 b/read = 2 x 10^9 b.
Error rate (general ballpark for RNA replication/translation, number comes from personal experience in the field and memory of published data) = 1 x 10^-5 errors/b
Expected number of detectable errors = 2 x10^9 * 1 x 10^-5 = 2 x 10^4, that's within order of magnitude from observed rate! Practically an exact hit in molecular biology.
Randomness of distribution of errors: should not be random. Several described and known factors impact frequency of errors, such as base composition around the site, secondary and tertiary structures of RNA and DNA (yes, even DNA! although many seem to believe that DNA is a plain old double stranded DNA, it does have a tertiary structure, including during transcription to RNA).
This statistical analysis (albeit a brief one) does not disprove the presence of RNA -editing, but might emphasize the need for a more careful analysis and interpretation of data. RNA editing has been described before, and in some cases plays a vital role in making an organism function at all (e.g. some viruses have RNA-editing to regulate activity of polymerases and expression of viral proteins).
In conclusion, it is not an earth-shattering, dogma overthrowing finding, but rather an additional piece of information about expression of the genome and translation of it into phenotype.
Just in case one thinks that I do not know what I am talking about, here are my credentials:
my @a = ('A'..'Z', " ",'a'..'z');
my @r = (15, 7, 3, 26, 12, 41, 38, 31, 29, 47, 38, 27, 44, 26, 1, 35, 41, 38, 41, 33, 51);
map {print $a[$_];}(@r);
print "\n";