Monday, May 30, 2011

The Central Dogma Strawman

Whenever you're trying to promote a new idea it's nice to have a scapegoat to beat up on. You're going to get a lot more attention if you can demonstrate that your latest results overthrow some key scientific concept that everyone took for granted. If you can't find a real "key concept" then the next best thing is to make one up.

For the past several decades that strawman target has been The Central Dogma of Molecular Biology. The Central Dogma is supposed to represent the key concept of molecular biology yet it gets "overthrown" on a regular basis every six months. Isn't that strange?

The latest example comes from a Nature review of a recent Science paper. The Science paper presents evidence that many mRNA sequences differ from the sequences in the exons that encode them (Li et al., 2011). RNA editing has been known for decades and every few years it is trotted out again as proof that the Central Dogma is wrong. The recent Li et al. (2011) paper doesn't present evidence for a new phenomenon but it does suggest that RNA editing may be much more common than previously suspected.

Here's what Nature staff writer Erika Check Hayden says about this paper ("Cells may stray from 'central dogma'" Hayden, 2011a).
All science students learn the 'central dogma' of molecular biology: that the sequence of bases encoded in DNA determines the sequence of amino acids that makes up the corresponding proteins. But now researchers suggest that human cells may complicate this tidy picture by making many proteins that do not match their underlying DNA sequences.
Now if that really was what the Central Dogma actually said then it would have disappeared thirty years ago.

The real Central Dogma of Molecular Biology is ...
... once (sequential) information has passed into protein it cannot get out again (F.H.C. Crick, 1958)

The central dogma of molecular biology deals with the detailed residue-by-residue transfer of sequential information. It states that such information cannot be transferred from protein to either protein or nucleic acid. (F.H.C. Crick, 1970)
I've explained why this is the correct version in an old blog posting from 2007: Basic Concepts: The Central Dogma of Molecular Biology. A very similar definition can be found on the Wikipedia site: Central Dogma of Molecular Biology. The key point is that once information flows into protein it can't flow back to nucleic acid. The standard misconception of the Central Dogma is actually the normal information flow pathway or what Crick called the "Sequence Hypothesis." It's a generality that was never meant to be an inviolate rule like the actual Central Dogma.

Hayden has another article in this week's print version of Nature (Hayden, 2011b). The second article emphasizes the controversy surrounding the Li et al. (2011) paper—lots of people are skeptical—but she doesn't back off the implications.
If verified, the findings would require a rewrite of the 'central dogma' of molecular biology, which posits that the RNA transcripts that carry genetic information to the ribosome, where they are used as templates for protein assembly, are generally faithful matches to the original DNA.
There are two remarkable things about such a statement. First, RNA editing has been an established fact for almost thirty years so if the Central Dogma needed rewriting it would have been done a long time ago. Second, Hayden was informed in the comments to her first article that there was a problem with her definition of the Central Dogma. Maybe she didn't have time to change the second version that was about to be published.

To be fair, this isn't just a problem with science writers who don't do their homework. Hayden is right when she says that most science students learn an incorrect version of the Central Dogma of Molecular Biology. It's true that most textbooks promote the information flow pathway as the Central Dogma and they fail to point out that the real version only precludes reverse translation. I don't understand why so many textbook writers and teachers continue to teach something they know to be false as the "Central Dogma" of molecular biology.

Is it because they don't know about the exceptions?


Crick, F.H.C. (1958) On protein synthesis. Symp. Soc. Exp. Biol. XII:138-163.

Crick, F. (1970) Central Dogma of Molecular Biology. Nature 227, 561-563. [PDF file]

Hayden, E.C. (2011a) Cells may stray from 'central dogma.' Nature Published online 19 May 2011 [doi:10.1038/news.2011.304.

Hayden, E.C. (2011a) Evidence of altered RNA stirs debate. Nature 473:432. [doi:10.1038/473432a]

Li, M., Wang, I.X., Li, Y., Bruzel, A., Richards, A.L., Toung, J.M., and Cheung, V.G. (2011) Widespread RNA and DNA Sequence Differences in the Human Transcriptome. Science. 2011 May 19. [Epub ahead of print] [Science]

76 comments :

  1. I agree that this is what the Central Dogma should be thought to be, and technically is, but it would not be hard to find, for instance, chapter titles like "The Central Dogma" for chapters of books written by important smart gene experts that explain that the specific "degenerate" code for 20 amino acids and stop signals IS a key part of the central dogma.

    This google search demonstrates my point: http://tinyurl.com/3rrj3yu

    What we have here is an excellent example of the reporting of science relying on the dialectic of overthrowing "everything you thought you knew" rather than simply describing the important finding which might be rather interesting in and of itself.

    But the aspect of whether or not someone is correct in defining the central dogma, might be a red herring. Which is what straw men eat, apparently, as a side dis with their wild geese.

    ReplyDelete
  2. As your own old post makes clear, at the heart of the matter is that Watson's version of the "dogma" is simply much more popular. So what if it's been discarded on a regular basis? Watson was always much better than Crick at self-promotion, so it's almost expected that his version attracted more attention. Besides, it provides the bonus for being able to sex up new findings by dismantling the dogma. Crick's version? Bo-ooring.

    ReplyDelete
  3. http://www.nature.com/news/2011/110519/full/news.2011.304.html
    "It was already known that some cells 'edit' RNA after it has been produced to give a new coding sequence, but the new work suggests that such editing occurs much more often in human cells than anyone had realized, and that hitherto unknown editing mechanisms must be involved to produce some of the changes observed. If the finding is confirmed by other investigators — and some scientists already say they see the same phenomenon in their own data — it could change biologists' understanding of the cell and alter the way researchers study genetic contribution to disease."
    "It's really exciting, because this study reports a different variety of RNA editing that is much more widespread than existing mechanisms," Nishikura says.

    ReplyDelete
  4. Here is a quote from one of the comments:
    http://www.nature.com/news/2011/110519/full/news.2011.304.html#B1
    "RNA editing has already been found in a number of organisms and is carried out by a number of mechanisms involving either guide RNAs (gRNAs) or enzymes although there may, of course, be other mechanisms yet to be found if it is indeed as common as this study hints. There is evidence for extensive transcription of noncoding segments of our genome and its possible that some of these rnaS may be involved in editing in some way analagous to gRNAs.

    ReplyDelete
  5. @anonymous,,

    There are many scientists who don't believe that most of our genome is junk. It's not necessary to quote them every time they make a comment.

    In my experience these scientists are not very knowledgeable about genome organization and they couldn't defend their opinion if challenged. Nevertheless, the debate over the existence of copious amounts of junk DNA is very much a genuine scientific debate no matter what the IDiots have told you.

    ReplyDelete
  6. Dr. Moran is missing the point. This study has opened up the possibility that a large amount of what has been called "junk DNA" (and "junk RNA") may well be involved in the RNA editing that the study has potentially found.

    This is the way science progresses. By learning new things and new functions. Not by profs who keep asserting that when we have not yet found the function we should consider it junk.

    But Dr. Moran seems has a large personal stake in this issue so he is not objective.

    ReplyDelete
  7. Mr. Anonymous is fast at ad hominen without realizing that Mr. Anonymous himself also has large personakl stakes at the issue.

    But the question remains open begging for evidence. ¿Is there any evidence of the extensive involvement of non-coding DNA (intronic DNA, transposon-like DNA) in editing? Not at all. What Mr. Anonymous cites in in bold is merely a conjeture, a guess, a desire. Desires are not proof.

    ReplyDelete
  8. Anonymous writes:

    Dr. Moran is missing the point. This study has opened up the possibility that a large amount of what has been called "junk DNA" (and "junk RNA") may well be involved in the RNA editing that the study has potentially found.

    If you understood the concepts of protein synthesis, you wouldn't be pushing the putative findings of this article, which actually are pretty deadly for the design concept if true.

    Let's go over a brief summary explanation once again. DNA acts as a template for RNA, which then has to be extensively edited (the RNA corresponding to the DNA intron regions is thrown out) in order to use the RNA as a template for protein.

    What this article is saying is that there is extensive use of other RNA to make many additional edits before protein is synthesized - in other words, under the regime proposed by this paper, the final protein resembles the original DNA template even less than in the "classic" synthesis.

    This has two implications that, if true, would be extremely problematic for the design concept:

    - Particular regions of DNA code may be less necessary to the final protein product than we've thought, i.e., perhaps more, not less, should be classified as "junk."

    - The most efficient design process would be to have a DNA template that is then reproduced faithfully in the process of making protein. But we know that in many living things, huge amounts of RNA coded by DNA introns must be thrown out before protein is synthesized. Messy and inefficient. Now this paper says there are yet additional steps where yet other RNA changes the template before protein synthesis can take place. Messy, verging on chaotic. Certainly not an example of what a good designer would choose to do.

    ReplyDelete
  9. Anonymous spouts,

    Dr. Moran is missing the point. This study has opened up the possibility that a large amount of what has been called "junk DNA" (and "junk RNA") may well be involved in the RNA editing that the study has potentially found.

    Let's be generous and assume that every single mRNA needs two guide RNAs. Typical guide RNAs are 10-20 nucleotides in length but we'll be generous (again) and assume that they're 100 bp long. That's 200 bp of guide RNAs per gene.

    There are 20,500 protein-encoding genes in our genome. That means a (generous) total of 20,500 X 200 = 4,100,000 bp of guide RNA. The DNA for all these guide RNAs would make up 0.13% of the genome.

    Is this how the IDiots think they're going to explain junk DNA? No wonder we call them IDiots!

    ReplyDelete
  10. What the commenter said and I bolded is an hypothesis. An hypothesis that could be tested.

    Am I right in thinking that such an hypothesis should be tested or would those who believe so strongly in junk DNA suggest this hypothesis not be tested?

    ReplyDelete
  11. For some reason Moran, is positioning this subject as an anti-ID discussion.
    Some of us are interested in this subject just from the point of view of determining whether what is called "junk DNA" may indeed have a function.
    That is a scientific inquiry.

    ReplyDelete
  12. Maybe, at least, Li's paper will overthrow the false version of the Central Dogma?
    But probably not, since you've stated its been 'overthrown' dozens of times.
    Also, notice how the textbook illustration of Central Dogma is quick to point out that 'dogma' is a misnomer, but then it presents the incorrect version of the dogma.
    Its trendy to displace dogmas, being correct, not so trendy.

    ReplyDelete
  13. Anonymous states:

    "Dr. Moran is missing the point. This study has opened up the possibility that a large amount of what has been called "junk DNA" (and "junk RNA") may well be involved in the RNA editing that the study has potentially found."

    First of all, the original statement was merely that "some of these rnaS[sic] may be involved in editing in some way analagous to gRNAs" (emphasis added). Not "a large amount" as you would have it - "some."

    Second, the statement was from the unmoderated online comments to a naturenews story. That doesn't exactly carry a lot of evidentiary weight. No disrespect intended to the original commenter, of course. He was merely speculating, which is fine. It's not his fault that you want to pretend his speculation is evidence for your preconceived belief.

    ReplyDelete
  14. Hello Dr. Moran.
    Can you please explain how you arrived at "The DNA for all these guide RNAs would make up 0.13% of the genome"?

    ReplyDelete
  15. qetzal, perhaps you missed my post:

    "What the commenter said and I bolded is an hypothesis. An hypothesis that could be tested.

    Am I right in thinking that such an hypothesis should be tested or would those who believe so strongly in junk DNA suggest this hypothesis not be tested?"

    ReplyDelete
  16. Professor Moran,

    Check out fig 26-32 in the 5th Edition of Lehninger. It shows RNA dependent synthesis of RNA and DNA. The figure is identical to the Central Dogma Wikipedia article you referenced.
    The figure you reference is on page 945. I have no idea why Nelson and Cox did not include a reference to pg 1050 on page 950. it would have been less confusing, IMO.

    ReplyDelete
  17. Anonymous,

    If your post was up before I submitted mine, then I did indeed miss it. My apologies for that.

    Yes, what the commenter said is a hypothesis. However, I'll remind you that the commenter's hypothesis was that some of those transcripts might be involved in RNA editing. Your hypothesis was that most of those transcripts might be involved. The commenter's hypothesis is reasonable, and even likely. Yours seems very unlikely to me.

    Should either hypothesis be tested? Sure, albeit indirectly. I wouldn't set out to specifically test whether some or most of the 'junk RNA' transcripts are used for editing. Instead, I would simply look for the possible guide RNAs. If and when they are found, they should certainly be mapped in the genome. That will tell us their relationship to 'junk RNA.'

    ReplyDelete
  18. > The key point is that once information flows into protein it can't flow back to nucleic acid.

    Sure it can! It's called evolution.

    For example, DNA makes the proteins, and those proteins acting on other proteins may pronounce "That's a bad strand of DNA, it must needs be suppressed."

    ReplyDelete
  19. Hello Dr. Moran.
    Can you please explain how you arrived at "The DNA for all these guide RNAs would make up 0.13% of the genome"?

    ReplyDelete
  20. @ Anonymous Wednesday, June 01, 2011 10:02:00 AM

    The math is in the 3rd paragraph...

    ReplyDelete
  21. It looks like Moran will not be explaining how he arrived at
    "The DNA for all these guide RNAs would make up 0.13% of the genome"?".

    Pity. It would be very educational.

    ReplyDelete
  22. I am becoming concerned that Moran may have realized that he said something wrong and just wants this to go away quietly.
    I do not know how he came up with his calculation or whether it is correct.
    But I am interested in having Moran explain it.
    That would be very educational.

    ReplyDelete
  23. @ Anonymous Thursday, June 02, 2011 9:39:00 AM

    Sticking your fingers in your ears and screaming I can't hear you won't cut it here.

    Larry Moran wrote;
    9th comment, 2nd - 3rd paragraph
    "Let's be generous and assume that every single mRNA needs two guide RNAs. Typical guide RNAs are 10-20 nucleotides in length but we'll be generous (again) and assume that they're 100 bp long. That's 200 bp of guide RNAs per gene.

    There are 20,500 protein-encoding genes in our genome. That means a (generous) total of 20,500 X 200 = 4,100,000 bp of guide RNA. The DNA for all these guide RNAs would make up 0.13% of the genome."

    ReplyDelete
  24. Anonymous I am not asking for you to repeat the earlier post. I am asking Moran to explain it.

    ReplyDelete
  25. Anonymous writes:

    I am asking Moran to explain it.

    What is it that you don't understand?

    ReplyDelete
  26. Since Moran accepts and posts the entries we submit, he knows that I have been asking him to explain how he arrived at:
    "The DNA for all these guide RNAs would make up 0.13% of the genome."

    But he is not explaining it.
    We must conclude that he cannot explain it.

    ReplyDelete
  27. @Anonymous Thursday, June 02, 2011 11:20:00 PM

    Actually, all this is proving is that you don't even get the second letter capitalized in "Idiot".

    ReplyDelete
  28. @Anonymous
    No body has bother answering you because the maths for how Dr. Moron arrived at his figure should be crystal clear to anyone with a reading age above ten. Total genome size equals ~3Gbp.
    4,100,000bp/3000000000bp x 100=0.13%

    ReplyDelete
  29. Once again, Anonymous:

    What is it that you don't understand?

    ReplyDelete
  30. If that is all that was required why the reluctance of Moran to say it?
    In fact much more needs to be explained.

    But since Moran is not able or willing to do it there is not much point in continuing to discuss it.

    It seems that generally I know more about evolution theory than the people here. That is why they generally do not want to make any constructive assertions since then I show how they do not stand up.

    We see how when Moran made a constructive assertion it turned into a fiasco in the thread:
    Junk & Jonathan: Part 4—Chapter 1
    http://sandwalk.blogspot.com/2011/05/junk-jonathan-part-4-1.html

    ReplyDelete
  31. This study has opened up the possibility that a large amount of what has been called "junk DNA" (and "junk RNA") may well be involved in the RNA editing that the study has potentially found.

    This is the way science progresses. By learning new things and new functions. Not by profs who keep asserting that when we have not yet found the function we should consider it junk.

    ReplyDelete
  32. Moran and others here turn any discussion into an argument. Which is a pity.

    Here is a review:
    http://www.nature.com/news/2011/110519/full/news.2011.304.html
    "It was already known that some cells 'edit' RNA after it has been produced to give a new coding sequence, but the new work suggests that such editing occurs much more often in human cells than anyone had realized, and that hitherto unknown editing mechanisms must be involved to produce some of the changes observed. If the finding is confirmed by other investigators — and some scientists already say they see the same phenomenon in their own data — it could change biologists' understanding of the cell and alter the way researchers study genetic contribution to disease."
    "It's really exciting, because this study reports a different variety of RNA editing that is much more widespread than existing mechanisms," Nishikura says."

    AND

    And an hypothesis:
    ""RNA editing has already been found in a number of organisms and is carried out by a number of mechanisms involving either guide RNAs (gRNAs) or enzymes although there may, of course, be other mechanisms yet to be found if it is indeed as common as this study hints. There is evidence for extensive transcription of noncoding segments of our genome and its possible that some of these rnaS may be involved in editing in some way analagous to gRNAs."

    Note some points that people have not clued in to:
    The study hypothesizes that there may be a "hitherto unknown editing mechanisms involved ".
    Perhaps there is.

    And note the commenter I quoted says that it might be ANALOGOUS to
    gRNAs.
    These are exciting ideas. But Moran and others who think as he does, just want to tamper that down. They have their agenda that almost all DNA is junk and are not interested in finding out what function they may actually have.
    Which is really a pity.

    ReplyDelete
  33. Curiously whenever I read something by Anonymous (aka Anus.) the IDiot that image of the armless and legless Black Knight keeps coming to my mind ...

    ReplyDelete
  34. Anonymous writes:

    It seems that generally I know more about evolution theory than the people here.

    "It seems that generally I know more about brain surgery than the people here."

    "It seems that generally I know more about rocket science than the people here."

    "It seems that generally I know more about quantum field theory than the people here."

    Whenever I run into people who make statements like these, I make very sure not to have to rely on them for anything, particularly not in the field of their claimed "expertise." It takes a very special, arrogant sort of fool to discount everything he or she doesn't know.

    ReplyDelete
  35. Anus. The IDiot said,

    If that is all that was required why the reluctance of Moran to say it?

    Well, one would guess that you have the math skills to calculate that yourself. But it seems you don't even have the skills to notice when you are just being so stubbornly ridiculous that it becomes natural for people to start ignoring you. Just like in the other thread where you insist on asking about the loss of those genes as if the explanations did not make sense, when it is so clear that your idiocy is what does not make sense. Are you for real? I can't believe someone can be that incredibly stupid, nor can I guess why would you want so badly to portray yourself at such a low level. IDiot dishonesty, I have witnessed. Some level of stupidity on their part, well, witnessed too. But this much imbecility on your part, portrayed with so much gusto, so obvious and concentrated, I just can't figure out why or how.

    But enough is enough. Adios IDiota.

    ReplyDelete
  36. Anonymous writes:

    In fact much more needs to be explained.

    Since you refuse to say anything at all about what that "much more" is, while bleating on and on about it, it's very obvious to the rest of us that the bleating, not the explanation, is the point.

    So you may as well not continue to waste the effort - or you can, if that style of self-satisfied, dramatic, wholly artificial complaint is what floats your boat.

    ReplyDelete
  37. I have posted ideas. Others here have posted insults and vulgarities.
    That is your choice.
    But go ahead and justify yourselves.

    ReplyDelete
  38. This anonymous is a very effective troll. I must say I'm a small bit impressed.

    ReplyDelete
  39. Calling someone a "troll" means that you have nothing constructive to contribute yourself but want to say something derogatory.

    ReplyDelete
  40. @Anonymous
    I'm still not seeing what you want explained. Even if we assumed that the portion of the genome dedicated to gRNA is equal to total coding DNA (which is absolutely absurd) then gRNA would still only make up 1.5% of the genome. It is totally impossible that functional gRNA makes up any significant fraction of the genome.

    If you disagree, please explain what conceivable advantage having in excess of fifty distinct gRNA sequences for every gene would provide?

    ReplyDelete
  41. Please explain what you mean by "calling someone a "troll"". If you can't then you're invalid.

    ReplyDelete
  42. Boojum, I wasn't asking you. I was asking Moran.

    If you want to post your thoughts feel free. For example what are your thoughts about the idea that:

    It was already known that some cells 'edit' RNA after it has been produced to give a new coding sequence, but the new work suggests that such editing occurs much more often in human cells than anyone had realized, and that hitherto unknown editing mechanisms must be involved to produce some of the changes observed.

    ReplyDelete
  43. When people want to only confirm their existing thinking, they shut down their thinking. They have no creative thoughts, no new ideas.
    Everything is boiled down to fit into their current thinking.
    This is a very common human tendency.

    I approach this differently. I say to myself - do we understand why all the things that occur in the cell happen as they do? Do we understand how those cellular functions obtain the information they need and how they are controlled?
    Then I ask myself - where could the control and the information be coming from?
    Then I notice that a great deal of non-coding DNA is transcribed.
    Then I start to think about how could these possibly go together.

    What I am doing is called science. What the people here are doing is called dogmatism.

    ReplyDelete
  44. "There are 20,500 protein-encoding genes in our genome. That means a (generous) total of 20,500 X 200 = 4,100,000 bp of guide RNA. The DNA for all these guide RNAs would make up 0.13% of the genome."

    So 4,100,000 bp of guide RNA is produced by 4,100,000 bp of DNA?
    Is that correct? A one to one correspondence?

    ReplyDelete
  45. @Anonymous
    It is clear to everyone that all you are doing is refusing to accept facts because they don't fit into your religious paradigm.

    No one is disputing that there are segments of the genome with still to be discovered function, but it does not follow from this that the entire genome must be functional. Especially when there is substantial body of evidence indicating that large portions of the genome are totally nonfunctional.

    As has now be pointed out to you multiple times function gRNA coding regions do not make up significant portion of the genome. We can be absolutely certain of this fact because protein sequences do not on average diverge substantially from the DNA coding sequence.

    Your continued quibbling over an extra 0.1% here and 0.001% there as if this somehow magically explains away the 90% of DNA believed to be nonfunctional,does not mark you out as a scientist but as a religious ideologue. Trying to shoehorn facts into a predetermined and non-evidence based answer.

    Before you accuse others of dogmatism try looking in a mirror.

    ReplyDelete
  46. Anonymous writes:

    What I am doing is called science.

    Say what?

    You're a blog commenter with delusions of grandeur! :-D

    ReplyDelete
  47. Moran posted:
    "There are 20,500 protein-encoding genes in our genome. That means a (generous) total of 20,500 X 200 = 4,100,000 bp of guide RNA. The DNA for all these guide RNAs would make up 0.13% of the genome."

    So 4,100,000 bp of guide RNA is produced by 4,100,000 bp of DNA?
    Is that correct? A one to one correspondence?

    Anyone can answer this question.

    ReplyDelete
  48. @Anon. Saturday, June 04, 2011 10:17:00 PM

    Honestly....

    He is not making the claim of a 1 to 1 correspondence. He is saying (paraphrased) even if there is an outrageous amount of this, it would only account for 0.13% . So this is a red herring. A useless exercise. This phenomenon, even if widespread, does not even dent the ~26% of "unknown" that is left.

    ReplyDelete
  49. The .13% of the genome is calculated as 4,100,000 bp of RNA divided by 3,200,000,000 bp of DNA.

    So in fact, Moran is saying that 4,100,000 bp of guide RNA is produced by 4,100,000 bp of DNA.

    Right?
    Either people did not notice this or they did notice and quietly went along.

    Now come the excuses.

    ReplyDelete
  50. @anonymous,

    I should have said 4,100,000 nucleotides of guide RNA (not bp). Is that what this is all about?

    ReplyDelete
  51. So you are saying that 4,100,000 nucleotides of guide RNA is produced from 4,100,000 nucleotides of DNA?
    Is that it?

    ReplyDelete
  52. Anonymous wrote:

    Boojum, I wasn't asking you. I was asking Moran.

    Anonymous later wrote:

    Anyone can answer this question.

    So you're now in charge of who gets to respond to comments on Dr. Moran's blog?

    Must you practice to be this obnoxious or does it come naturally?

    Now, since you're allowing us all to answer, let me take a shot at what I think the answer is, and someone will tell me if I'm wrong.

    A one-to-one correspondence is the highest DNA-to-RNA ratio possible, and thus 4.1 million base pairs of DNA (.13% of the genome) is the most additional DNA that would not be considered junk. RNA editing or any other mechanism that changes the guide RNA nucleotides from what's in the DNA template would reduce the amount of DNA that winds up being reflected in the structure of the guide RNAs. So as he did all through his calculation, Dr. Moran erred on the side of additional functional DNA.

    ReplyDelete
  53. anonymous says,

    So you are saying that 4,100,000 nucleotides of guide RNA is produced from 4,100,000 nucleotides of DNA?
    Is that it?


    Do you have a specific question?

    I could guess at what your problem is but it would be far more helpful if you would just tell me.

    There are several possible scenarios that would require more DNA (e.g. promoters, secondary structure, multiple copies of guide RNA genes) but none of them makes much of a difference.

    ReplyDelete
  54. Moran posted:
    "There are 20,500 protein-encoding genes in our genome. That means a (generous) total of 20,500 X 200 = 4,100,000 bp of guide RNA. The DNA for all these guide RNAs would make up 0.13% of the genome."

    The .13% was calculated by dividing 4,100,000 bp of guide RNA by 3,200,000,000 bp of DNA.
    Note the RNA in the numerator and the DNA in the denominator.

    For this to be a valid calculation of genome percentage, the units must be both DNA units.

    So the first question is how much DNA bp are required to produce 4,100,000 bp of guide RNA?
    Then divide that number by 3,200,000,000.

    That is how to calculate a valid percentage of genome.

    Is there someone here who did not realize this or is everybody just pretending?
    And spare us the excuses.

    If you are going to calculate to two decimal places at least know what you are doing.

    ReplyDelete
  55. Dr. Moran writes:

    There are several possible scenarios that would require more DNA (e.g. promoters, secondary structure, multiple copies of guide RNA genes) but none of them makes much of a difference.

    Thanks for the correction.

    ReplyDelete
  56. Anonymous writes:

    For this to be a valid calculation of genome percentage, the units must be both DNA units.

    No! You don't say! What are "both DNA units"?

    Oh, you mean they must both be DNA units.

    Glad I could help you with your English grammar skills in return for you showing me how to do math!

    ReplyDelete
  57. Now that people's thinking has been corrected about this calculation*, we can look at the question concerning introns that is posted here:
    http://sandwalk.blogspot.com/2011/05/whats-in-your-genome.html?showComment=1307215457419#comment-c7407141412117820523

    * We still have not calculated the correct value. It is of course not .13%.

    ReplyDelete
  58. anonymous says,

    We still have not calculated the correct value. It is of course not .13%.

    Please don't keep us in suspense any longer.

    What value does Intelligent Design Creationism predict?

    ReplyDelete
  59. Moran this is not an ID issue. It is an evolution issue.

    I would look to you to tell us how much DNA is required to produce 4,100,000 bp of guide RNA.

    Take into consideration that the DNA contains introns which are spliced out.
    So the DNA required would be just under double, it would seem.
    On this specific question you really can contribute.

    ReplyDelete
  60. I would look to you to tell us how much DNA is required to produce 4,100,000 bp of guide RNA.

    Take into consideration that the DNA contains introns which are spliced out.

    So the DNA required would be just under double, it would seem.


    Please do clue us in regarding what linguistic or scientific usage equates "required to produce" with "spliced out."

    ReplyDelete
  61. @ Anonymous Monday, June 06, 2011 11:52:00 AM

    If I were a pedantic ass like other Anonymous posters, I would point out that DNA does not have introns... RNA does... ;-)

    Honestly, this is the depth of your contribution to the discussion.

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  62. http://en.wikipedia.org/wiki/Intron
    "An intron is any nucleotide sequence within a gene that is removed by RNA splicing to generate the final mature RNA product of a gene.[1][2] The term intron refers to both the DNA sequence within a gene, and the corresponding sequence in RNA transcripts."

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  63. Anonymous (aka Anus., the IDiot),

    Take into consideration that the DNA contains introns which are spliced out.

    No IDiot, the DNA "introns" are not spliced out. The introns in RNA are. (Since you like playing games with semantics you got what you deserve.)

    So the DNA required would be just under double, it would seem.

    It does not matter that the DNA for 4,100,000 nucleotide RNA is "double." The 0.13% is calculated for the length of DNA you imbecile, not counting but one strand.

    So, that RNA is one strand and DNA is two is not an issue. Your lack of intelligence for anything but rhetorical stupidity is.

    I can't believe how much of an imbecile can a creationist be.

    Can we all ignore this utter imbecile now? Can we ban the imbecile or do we need any more examples of the levels of stupidity attainable through creationism? I am truly just asking. If this display of imbecility is fun for you to witness, or tolerable, then I said nothing.

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  64. @Anon
    One, gRNA doesn't have introns you dolt there average length is only 20bp long. Two, what the hell was the point of all this? The 0.13 estimate was already extremely generous and even if we assume the amount of gRNA is double, triple or quadruple that it has no significant effect on the estimates of junk DNA within the human genome. It's like you've come dead last in a marathon and are squabbling with the officials about whether you finished at time fifteen hours and ten minutes or fifteen hours and nine minutes.

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  65. The point I am making about Moran's calculation of the .13% is that it is misconceived.
    That might be okay in a high school student but not so good in a prof who specializes in exactly this subject.

    But no doubt there will excuses. There always are.

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  66. Anonymous had time to respond to a later comment, but not my earlier question:

    "Please do clue us in regarding what linguistic or scientific usage equates 'required to produce' with 'spliced out.'"

    We're waiting....

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  67. Anonymous writes:

    The point I am making about Moran's calculation of the .13% is that it is misconceived.

    Oh, you had a point (you thought)?

    No, it's not misconceived. It's a ballpark estimate, with overly generous allowances for most of the factors, showing that within any conceivable magnitude of variation, the DNA that would ostensibly make all these guide RNAs doesn't amount to a pimple on the butt of the total genome.

    As you yourself quoted and bolded repeatedly, these are "hitherto unknown mechanisms;" and there is more than a little dispute about whether they even exist. Then you quibble about the amount of DNA it takes to make 4.1 million nucleotides of RNA. The reasons the rest of us aren't bothering are (1) it was a proof-of-concept ballpark calculation; (2) because of #1, it's impossible to be certain exactly what the DNA-to-RNA ratio would be; and (3) whatever the variation in the ratio, it's so small - some fraction of .13% - as to be utterly insignificant.

    That much was obvious to the rest of us from the beginning. Your obsessive concentration on this insignificant item can only be attributed to insincerity - you knew it made no material difference, but you decided to try to make a big deal of it anyway - or such complete lack of understanding as I've never seen in the comments on this blog before.

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  68. Jud recognizes that the calculation is misconceived and not simply an arithmetic error. That is good.
    Does everyone see that now?

    But go ahead and pretend you saw that from the beginning. (If so, why did nobody admit it then).
    What a laugh you folks are.

    And nobody has yet acknowledged that a prof specializing in this field should not misconceive such a calculation in the fist place.

    And by the way this misconception applies to other percentages Moran has calculated. Will anyone admit that?

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  69. To clarify a sentence from my last comment:

    whatever the variation in the [DNA-to-RNA] ratio, the resulting difference in the amount of DNA that would be used to make the guide RNAs is so small - some fraction of .13% - as to be utterly insignificant.

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  70. I wrote of Dr. Moran's ballpark calculation:

    No, it's not misconceived.

    Anonymous responded:

    Jud recognizes that the calculation is misconceived and not simply an arithmetic error.

    OK, that certainly clears up a lot. Whenever you read something, you think it says the precise opposite of the actual meaning.

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  71. Is everyone going to continue to pretend?
    The calculation is misconceived because it divides RNA by DNA and then claims the result is a percentage of the genome.
    That is a misconception.
    People can try excuse after excuse if you wish.

    By the way this misconception applies to other percentages Moran has calculated.

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  72. My apologies for interrupting this lovely "debate" and trying to discuss the science.

    Has anyone actually read the referred to Li et al. paper (doi 10.1126/science.1207018)?

    Doesn't it seem like they are reporting 15 interesting events where the RNA and protein don't match the DNA. But the rest looks suspiciously like RNA polymerase errors, compounded by RT-PCR errors, compounded with short-read sequence and bioinformatic errors? And finally followed up with the human inability to tell what "random" actually looks like? To call these events true RNA editing occurrences is a bit premature, isn't it?

    Isn't 15 single base events in hundreds of complete human genomes is a bit of a stretch to call "widespread"?

    /TheOtherJim
    (Having a problem with my Account...sorry for the Anonymous post).

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  73. The other Jim writes:

    Isn't 15 single base events in hundreds of complete human genomes is a bit of a stretch to call "widespread"?

    As I commented above, "there is more than a little dispute about whether they [the 'hitherto unknown RNA editing mechanisms'] even exist."

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  74. @ Jud
    I'm trying to stay away from the comments in the Nature Hype Machine articles. The paper itself is everything that I think is wrong in all this next-gen, high throughput data analysis. "My method is perfect, so all things I see are real biological events".

    I think your "more than a little" is quite an understatement.

    /TheOtherJim

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  75. I keep hearing about "splicing regulatory networks" from fellow grad students studying splicing, and I believe that the existence of specific splicing factor isoforms regulating specific splicing/editing events has been found and published. This demonstrates the flow of information from nucleic acid to protein, and back to nucleic acid. Thus I think this directly (as opposed to indirect arguments where evolution requires protein function to alter nucleic acid sequences) contradicts the "correct" statement of the central dogma, that information placed proteins cannot return to nucleic acids. Just my two cents.

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  76. @Louis,

    I don't understand why you think that nucleic acid binding proteins or nucleases are violations of the correct Central Dogma of Molecular Biology.

    Why is that any different than, say, DNA polymerase, that was known when Crick first formulated the Central Dogma? When we talk about "information" we are not talking about enzymatic activity.

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