Central Dogma of Genetics May Not Be So Central 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."
Re:Mutations (Score:3, Interesting)
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:Why is this news? (Score:3, Interesting)
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:Central Dogma? (Score:5, Interesting)
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:Why is this news? (Score:3, Interesting)
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? (Score:5, Interesting)
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.
More than one way to a result (Score:3, Interesting)
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.
Re:Central Dogma? (Score:3, Interesting)
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.
Not so Surprising... (Score:5, Interesting)
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:Central Dogma Barking Up Wrong Tree (Score:3, Interesting)
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:Why is this news? (Score:3, Interesting)
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:RTFA, the errors weren't random. (Score:2, Interesting)
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:NEWS FLASH (Score:1, Interesting)
The only claim this article actually makes is that the rate of errors is much higher than anticipated - something that is very interesting but hardly contradicts the notion that RNA copies from DNA.
Re:Central Dogma? (Score:3, Interesting)
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";
Re:Not so Surprising... (Score:2, Interesting)
That reminds me of an anecdote about genetic algorithms that Rick Riolo (U. Michigan) told during a complex systems seminar. He was part of a team in the 80s that was trying to use GA's to find the most fuel efficient autopilot possible for a specific airplane. They configured an industry standard simulation environment with a realistic gamut of weather conditions, etc etc. and left the GA running for a few weeks. When they came back, they were surprised to find all the surviving autopilots had more fuel than the plane started with: the GA had found a bug in the simulator.