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I was recently reading about non-coding RNAs being a counter example to Central Dogma of Biology. Can someone add more cases which violate the Central Dogma? Thanks!

UPDATE - Reference of lncRNAs violating Central Dogma:

Although the central dogma remains a core tenet of cellular and molecular biology, the appreciation of lncRNAs as functional genomic elements that defy the central dogma may be essential for fully under- standing biology and disease. [Iyer et al. Nature, 2015]

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  • $\begingroup$ No, neither of those are counterexamples to the central dogma, as stated by Francis Crick: the dogma only says that information does not flow from protein back to DNA and RNA. Crick was well aware of RNA viruses. See his paper nature.com/nature/focus/crick/pdf/crick227.pdf $\endgroup$
    – Roland
    Commented Jul 28, 2016 at 8:07
  • $\begingroup$ @Roland Thanks for highlighting the virus thing. Please have a look at updated question (with reference of statement) $\endgroup$
    – Failed Scientist
    Commented Jul 28, 2016 at 8:26
  • $\begingroup$ Well, I guess Iyer et al never looked up the original definition of the central dogma :) I know many textbooks have simplified / corrupted the concept to mean "DNA --> RNA --> protein", but that's a strawman ... In a sense it's just arguing about definitions, but to be correct, lincRNAs do not violate Crick's statement of the dogma. I suggest you read Crick's 1970 paper to get some context. $\endgroup$
    – Roland
    Commented Jul 28, 2016 at 9:01
  • $\begingroup$ Do not take it too seriously. Biologists - as most scientists - tend to find definitions for themselves and those are not always compatible with other definitions. And this also makes sense in the scientific progress, as otherwise you would have a hard time adapting theories and, as a consequence, definitions. Crick's definition is as far as I know not the common textbook definition most biologists might have in mind and therefore this is just an ongoing scientific debate, rather than an oathbreaker. ;) Make sure to use the definition you want to promote in publications. ;) $\endgroup$
    – AlexDeLarge
    Commented Jul 28, 2016 at 11:38
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    $\begingroup$ Talha. I've changed my view on that as I mention in my updated answer. I think there was a general misinterpretation of Crick's Central Dogma when Temin and Baltimore discovered reverse transcriptase, which evoked the reaction I expressed. (I was there at the time. Presumably there is a Nature News and Views article about it.) $\endgroup$
    – David
    Commented Jul 29, 2016 at 13:51

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Crick’s Central Dogma was actually:

The Central Dogma
This states that once ‘information’ has passed into protein it cannot get out again. In more detail, the transfer of information from nucleic acid to nucleic acid, or from nucleic acid to protein may be possible, but transfer from protein to protein, or from protein to nucleic acid is impossible. Information means here the precise determination of sequence, either of basesin the nucleic acid or of amino acid residues in the protein.

So, although in my comment I stated that the discovery of reverse transcriptase was the first violation of this — as was generally regarded — this turns out not to be the case.

I remember that the case of reverse transcriptase was felt to be different from the existence of RNA viruses because it involved the flow of information from RNA to genomic DNA, which were generally represented by a unidirectional arrow in the opposite direction in diagrams of the dogma. The following is a typical illustration of that, taken from some University lecture notes that I found on-line and which are described as:

These diagrams ..., created originally by Crick, summarize the basic processes of information transfer within cells.

Purported Crick diagram of central dogma 157

But the NCBI collection of facimilies of Crick’s documents include a 1956 diagram that is quite different and much more sophisticated:

Crick's actual 1956 diagram

And, so the central dogma has not been violated (certainly not by lncRNAs), unless you consider that it has by prions, where information of sorts is transfered from protein to protein.

Morals

  1. It’s amazing what you can find on the internet.

  2. Never believe what you find on the internet.

Footnote

I’ve seen the DNA → Protein arrow repeated as if it were fact in diagrams, although Crick only said ‘may’. I know of no example of this.

Cross Reference

I have just (June 2024) posted an answer to a different question about the Central Dogma on SE History of Science and Mathematics. It attempts to provide a historical context, but may be of more general interest.

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  • $\begingroup$ This is really enlightening, both biologically and philosophically (in terms of history of science). +1 $\endgroup$
    – AlexDeLarge
    Commented Jul 28, 2016 at 14:32
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    $\begingroup$ Loved the moral part, but David its Nature – not an XYZ sitting on internet and writing blogs. I have wrote the author email in this regard. Awaiting his [never coming] reply $\endgroup$
    – Failed Scientist
    Commented Jul 29, 2016 at 5:41
  • $\begingroup$ @TalhaIrfan — You're right to feel aggrieved, but a little explanation of how things work may help. When a paper submitted to Nature is sent out for review it will be because the authors claim to have made some substantial scientific progress. This will be expressed in the Title and the Summary of the paper, and the referees will be most concerned with whether the work is really important and whether it is correct. That is their main job. Hyperbole that only appears in the final paragraph of the discussion will often be ignored with a shrug of the shoulders. $\endgroup$
    – David
    Commented Jul 29, 2016 at 13:57
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The "Central Dogma" is an obsolete concept. It has no biological significance today. It's been outdated for decades since the discovery of reverse transcriptase, but it was never intended to be taken particularly seriously anyway; Crick deliberately gave it its portentous name as a provocative approach, to drive people to think more about the topic and look for the counterexamples he presumed were there.

Unfortunately, it seems that in some places -- notably India -- shoddy, ignorant teachers don't understand anything about modern biology and still believe that the Central Dogma has more than historical interest. It does not; it should not be taught in biology course, let alone treated as a testable concept, and any mention of it should be limited to History of Science courses.

Because it is an outdated concept that no longer matches modern biology, and because these ignorant teachers still try to squeeze it into their courses and tests, many students (again, especially from India) are very confused, thinking that their understanding is wrong because it contradicts the Central Dogma.

If you need to parrot something for an exam, I sympathize with you, but don't make the mistake of thinking that the Central Dogma is a real, relevant, modern biological concept.

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    $\begingroup$ I agree that there is no particular reason to mention the Central Dogma in teaching (and I never have myself), but it turns out that you are wrong about it being wrong in the way you say. I'm not criticising you, because I've only just discovered what Crick actually said and drew, as shown in my updated answer. $\endgroup$
    – David
    Commented Jul 28, 2016 at 14:17
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    $\begingroup$ Kind of makes the situation in India worse. Not only are these pedagogues insisting on teaching an outdated, irrelevant, biologically meaningless concept, they're not even teaching it correctly in the first place. $\endgroup$
    – iayork
    Commented Jul 28, 2016 at 15:24
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    $\begingroup$ — I don’t know about Indian universities but a comment by Anurag Chaurasia you may have seen in Nature recently would seem to express similar sentiments. I have been fortunate enought to have come in contact with students from India who have been most capable of critical thinking. $\endgroup$
    – David
    Commented Jul 28, 2016 at 15:46
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    $\begingroup$ That's my point. The people (often from India) who come to StackExchange with questions about the Central Dogma are obviously capable of critical thinking, because they are baffled by the useless, stupid garbage they're being taught. They usually don't understand that they're being taught garbage, but they do understand that it doesn't make sense, and they blame themselves for missing something. It's incredibly frustrating to see baffled question after question about the same thing, actively harming the understanding of clearly smart, clear-thinking people. $\endgroup$
    – iayork
    Commented Jul 28, 2016 at 16:48
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The central dog is an old 1950s concept that is obsolete and should be removed from the text box of the 2010s. It states that the flow of information from DNA->RNA->protein is unidirectional

Examples that goes against this idea are Reverse transcriptase which transcribes RNA -> DNA. Reverse transcriptase was originally found in RNA viruses. But has since been found in transposons which can be though of viruses that permanently resides in the host cell.

Telomerase... uses to elongate the ends of chromosomes from becoming shorter (something that occurs on the lagging strand of DNA during DNA synthesis) the shRNA used by this enzyme only encodes a few base pairs (6-8bp depending on kingdom)... but it is an example of RNA->DNA

RNA dependent RNA polymerase RNA-> RNA (No DNA is required to make more RNA). has been found in yeast.. with the role of maintaining the centromere... and likely will be found in humans too, since centromeric structure is believed to be conserved in the broad sense.

Prions. Where a prion serves as the template to cause a normal protein prion protein (PrPc) to undergo a change in folding and become the infectious prion (PrPsc). An example information in propagating between protein molecules. Protein-> protein

Then there is epigenetics... where proteins can leave methylation marks on genes (DNA)... changing the expression of the gene in an inheritable way. So information from proteins can flow upwards. While not DNA bases are changed, the DNA is modified. Protein -> DNA

There is also histone modification.. which can be inheritable depending on gene. But it is regulation of DNA by controlling how available that DNA is to being read by transcription machinery.

Then there is siRNA... which can and does modify gene activity. A weaker example of how information can flow from RNA -> DNA.

Next are proteins called cytidine deaminases. These proteins naturally convert cytidine to uracil. APOBEC modifies RNA.. creating a premature stop and thus a shorter APO-B protein with lower activity.. regulating lipid metabolism. So mRNA editing by APOBEC proteins changing the information in RNA aka Protein -> RNA. Next is AID, another cytidine deaminase but one that targets DNA. It used by the immune system to cause hypermutation and thus variation in the antibodies. A poor example of protein inducing genetic changes. Not controlled unlike the DNA methylation example.

Lastly there are ribozymes. RNA that have catalytic activity. So no need for the protein to catalyses a reaction.. RNA can do it on its own.

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    $\begingroup$ Jay - can you add some references to the terms you use in your answer? It would help other users follow along with what you are saying and definitely strengthen it. $\endgroup$
    – Vance L Albaugh
    Commented Sep 12, 2016 at 3:19
  • $\begingroup$ These are all interesting examples of regulatory interactions, but it is not at all clear that any of them contradict Crick's actual statements. $\endgroup$
    – Maximilian Press
    Commented Jun 5 at 18:27

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