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."

Comments

Why is this news?

[jd]

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?

[Artifakt]

I don't see why you claim there isn't a spell checker. Using DNA for the long term storage itself increases fidelity over RNA. Putting the DNA in a nucleus to protect it from some chemical processes that can cause data malformation also means an increase in fidelity. Multicellularity means (admittedly among other things), moving the reproductive cells deep in the organism so they are again protected from some more sources of copying errors. Simultaniously, it allows apoptosis (as there's no advantage for cell death in a single celled organism), and that's a second spell checker of sorts for multicelled organisms only. A lot of the more complex organism's defenses against diseases such as cancer could all be described as spell checkers (for example, P53 tumor suppressor). The form of DNA polymerase used in the complex organisms itself improves copying accuracy by about 100fold over what's possible for the non-eukarotes and even some of the fairly complex bacteria, and it's been described in operation as 'wiggling the part it has just put together to make sure it hasn't allowed the wrong base to pair before it moves on to the next bit, and having a digestive capability to strip out such mistakes when it finds them'. (See "Our Molecular Nature", by David Goodsell for more on this). Then there's snRNPs (Small Nuclear Ribonucleoproteins, which are formed to snip out introns from RNA copies for those RNA strands that aren't self splicing ribozymes (and of course rybozymes themselves even in organisms too simple to have snRNPs). It looks to me like most of the major changes in organic complexity are also spell checkers of one sort or another. I don't really like to anthropomorphise evolution as having long term goals, but it's probably at least as fair to say evolution is trying to produce totally accurate transcription, as it is to say it is trying to make organisms more ideally suited to their environments.

It's called an "error rate"

[sam_handelman]

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.

Re:RTFA, the errors weren't random.

[SETIGuy]

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.