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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."
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
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.
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)
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";