Friday, August 23, 2013

How IDiots Would Activate the GULOP Pseudogene

The enzyme L-glucono-γ-lactone oxidase is required for the synthesis of vitamin C. Humans cannot make this enzyme because the gene for this enzyme is defective [see Human GULOP Pseudogene]. The GenBank entry for this pseudogene is GeneID=2989. GULOP is located on chromosome 8 at p21.1 in a region that is rich in genes.

Here's a diagram that compares what is left of the human GULOP pseudogene with the functional gene in the rat genome.

Note the following features:
  1. The human pseudogene is missing the promoter and all of the regulatory sequences.
  2. The human pseudogene is missing exons I to VI.
  3. The human pseudogene is missing exon XI.
  4. There are several small deletions and in-frame stop codons in what is left of exons VII to X.
The IDiots don't like pseudogenes. They seem to think that pseudogenes are not compatible with the concept of Intelligent Design Creationism. Jonathan McLatchie thinks he has evidence that the human fetus can make vitamin C [A Simple Proposed Model For Function of the Human Vitamin C GULO Pseudogene]. That means that there has to be a special way of making the enzyme L-glucono-γ-lactone oxidase in early development.

This isn't a problem for Jonathan McLatchie. Here's how it could happen.
As I mentioned previously, the GULO gene in humans is rendered inactive by multiple stop codons and indel mutations. These prevent the mRNA transcript of the gene from being translated into a functional protein. If the GULO gene really is functional in utero, therefore, presumably it would require that the gene's mRNA transcript undergo editing so that it can produce a functional protein. It's not at all difficult to understand how this could occur.

Editing of mRNA transcripts is a widely recognized phenomenon in biology today. The mRNA transcript would presumably need to have the stop codons replaced with amino-acid specifying codons (as well as other edits of course to correct frame shifts caused by indels). The occurrence of such a process is not unheard of. For instance, the transcripts of tRNA and rRNA genes typically undergo editing to render them functional. And the mRNAs for mitochondrial proteins (e.g. NADH dehydrogenase 7; cytochrome c oxidase III) in Trypanosoma brucei -- the parasite that causes sleeping sickness -- are known to undergo extensive editing, in many cases being substantially rewritten to produce functional transcripts (Ochsenreiter et al., 2008; Piller et al., 1996).
Now there's a slight problem with this scenario since RNA editing requires RNA and, as far as I know, the human pseudogene isn't transcribed. Oh well, that's a minor quibble—I'm sure Jonathan McLatchie just forgot to explain how to get the transcript.

But there's another tiny flaw in his proposal. It's going to be a big challenge for RNA editing to create all those missing exons. I'm certain that Jonathan McLathie has thought about this. Maybe that part of the proposal was accidentally deleted from his post?

Here's the punchline, according to this IDiot.
If premature stop codons can be edited out of the mRNA transcript in this manner, thereby rendering functional what is otherwise a "pseudogene", this seems to me to have profound implications regarding not only GULO, but our understanding of pseudogenes in general.

If the hypothesis entertained here turns out to be correct, it will be yet another example of where a paradigm of design has led to fruitful scientific research. Of course, for ethical reasons, the hypothesis cannot be easily tested on humans. Guinea pigs also possess a GULO pseudogene with premature stop codons, however, and would make a good model organism for the testing of this hypothesis.
I look forward to the "fruitful research" that this "paradigm of design" will produce. If the IDiots actually discover an intelligent designer that can recreate missing exons in developing embryos (and then remove them in adults) then many of us are going to look very foolish.

Jonathan McLatchie is very excited about the work being done by Intelligent Design Creationists and the new technologies that will prove intelligent design.
Given that:
  • New technology suggests we're just standing on the shores of understanding a vast ocean of potentially functional pseudogenes,
  • It's highly feasible to understand how this pseudogene might have function,
  • Evidence suggests it might indeed have function during human development,
t would seem that [scientists'] claim that the GULO pseudogene is a "silver bullet" argument for evolution is highly premature. An ID-based paradigm of biology can help us understand the functions of pseudogenes, whereas a neo-Darwinian paradigm leads us to wrongly assume these genes like the GULO "pseudogene" are "broken" genetic "junk."
Do you still wonder why I call them "IDiots"?


44 comments:


  1. His evidence of fetal expression is from a paper in the 1950s that showed higher concentrations in the fetus ( fetal brain?) than in the mother. It didn't occur to him that the mother could be transporting it to the fetal by a mechanism other than simple diffusion. Still, I thought that though his idea is flawed at least he's trying to come up with ways to test ID. ( not that this really is a test of ID) I would have encouraged him to pursue this the way I would any bright, enthusiastic undergrad. Then I looked up the GULOP structure and saw its missing half the protein, including the FAD binding domain and an exon that flanks the active site and I thought WTF? He has an advanced degree, theres no excuse for mistakes like this

    RodW

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  2. Ha,
    I was just wondering if you picked up on this. The funny thing is that JM got soundly thrashed on the Glasgow Skeptic Facebook page and then blocked some of us for shredding this piece of "work".
    He was shown to lack basic critical reading skills. The first reference I checked was the Andersson one. He claimed to have read it and thought it was fine. I asked him about the data, the lack of stats and the lack of controls, and pointed out that, erm there was vitamin C in the diet and asked why he thought folk didn't get scurvey.
    He was criticised for not providing a test, and eventually came up with what would be an unfalsifyable answer.
    He then interrogated the ENSEMBL data base and claimed victory as there was a transcript. Turned out he hadn't bothered to read the supporting evidence bit - no RNA has been found
    He didn't like that and he blocked a few of us :-)

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  3. The intimidation instead of proof? Well, I had always wondered why people like Dan Growler survive... When his shi..t theory about JUNK DNA is discardecd, I will personally let Dan Brawler know abot it.cTust me ;0

    ReplyDelete
    Replies
    1. Only empty-headed individuals are intimidated by peer-review and criticism. JM (and his supporters) are free to comment here and defend their ideas, if they have any merit.

      Delete
  4. In his discussion with the Glasgow Skeptics on Facebook, JM said:

    "Btw, turns out I was overlooking the fact that GULO appears to be lacking a promoter and regulatory elements in humans. It's hard to see how it could produce a transcript."

    Ok, so here we go from a claim of the existence of a functional transcript, to a transcript that is produced by accident, to a transcript that could hardly ever be produced. These are the results of the fruitful research you were looking for, Larry.

    ReplyDelete
  5. Interesting to note that the ENV essay is still up and running with no disclaimers, updates or corrections.

    And of course no comments allowed. How many street-creationists will link to or refer to this as some sort of major ID-scientific triumph, only to later deny the exposure of the author's ignorance?

    ReplyDelete
  6. He has been challenged to print a retraction on this and other stuff (you should see how little he knows about codons).
    None are expected

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    Replies
    1. For the record, I always respond to criticisms of my work (as anyone who follows my writing should know). If I have made a mistake (as is the case here), I am happy to concede the correction. I read all critiques of my work that come to my attention. I am more interested in getting at the truth than I am in winning an argument. It's certainly not a habitual practice on my end to make mistakes like this... I'm usually more thorough.

      Delete
    2. @Jonathan Mclatchie

      So, what's your current position on whether the human GULOP pseudogene could produce a functional enzyme during early development? Do you agree that it's impossible?

      Delete
    3. JM,

      We're waiting for your retraction on ENV. A note, a disclaimer, a correction, or anything else that may properly inform the 200 or so gullible individuals who shared your article on social networks. They deserve to know the truth that you're getting at. They deserve to know that you made a mistake, and that you're honest and courageous enough to correct it publicly and in the same forum.

      Whether or not you're usually more thorough, that's another issue.

      Delete
    4. Larry,

      Yes, I think it is extremely unlikely.

      And yes, I will be posting something to that effect.

      Jonathan

      Delete
    5. I find it rather interesting, incidentally, that PZ Myers ignores what I write 99% of the time and virtually the only time he decides to engage with something I wrote is when I actually made a legitimate mistake.

      I had done extensive reading on RNA editing (which I still think could have important significance regarding unitary pseudogenes -- to be covered in a forthcoming article) but I hadn't been thorough enough with my reading regarding GULO. In any case, I am glad for the opportunity to be able to learn from this mistake...

      Delete
    6. Thanks Jonathan for upholding your honesty and integrity. You earned my respect. I'll be looking forward for the promised correction.

      Delete
    7. jonathan mclatchie said:

      "I am more interested in getting at the truth than I am in winning an argument."

      Then wouldn't it be a good idea for you to actually learn something before presenting your articles and arguments?

      If you're "more interested in the truth", why don't you admit in all of your articles and arguments that your religious beliefs are what drives you to dispute evolution and evolutionary theory? And if you're "more interested in the truth" then why do you align yourself with ID pushers who are obviously lying about their religious motives and agenda?

      I am continually amazed that ID-creationists like you apparently think that you're fooling intelligent, educated, observant, scientifically minded people into believing that you're knowledgeable and supportive of science and aren't just trying to replace science (or at least certain parts of it) with your non-scientific dominionist agenda.

      Delete
    8. Jonathan: I am more interested in getting at the truth than I am in winning an argument.

      Cough up the truth then. The truth... indeed... seems to be... that GULOP is a functionless piece of "junk" DNA. Is that correct?

      Delete
    9. @ Jonathon Mclatchie,

      So how does "design theory" explain the presence of the of the GULOP pseudogene in the human genome? Why did God put it there?

      Delete
    10. "For the record, I always respond to criticisms of my work (as anyone who follows my writing should know). If I have made a mistake (as is the case here), I am happy to concede the correction."

      No you don't.
      Remember this quote?

      "Indeed, the genetic code found in nature is exquisitely tuned to protect the cell from the detrimental effects of substitution mutations. The system is so brilliantly set up that codons differing by only a single base either specify the same amino acid, or an amino acid that is a member of a related chemical group."

      I responded
      ""Let’s now really demolish your claim with some facts. Here are some examples, there are many more. Let’s play how many you can find.

      Valine (polar uncharged) to Phenylalanine (hydrophobic) substitute GUU or GUC to uUU or uUC
      Valine (polar uncharged) to Glutamic acid (anionic) GUA or GUC to GaC or GaA

      Isoleucine (hydrophobic side chain) to Threonine (polar uncharged and now a possible phosphor acceptor site) AUU or AUA or AUC to AcU or AcA or AcC.

      Theonine (polar uncharged, loss of possible phosphoregulatory site) to Lysine (cationic, potential, methylation, acetylation, ubiquitylation, sumolyation, ISGylation, NEDDylation site ) ACA or ACG to AaA or AaG.

      What’s that, I hear you say? Yes, it does facilitate the co-evolution of new pathways and crosstalk."

      Where was the retraction?

      Delete
    11. Clearly, we know you are incompetent, but your fellow creationists are already calling this debacle evidence.
      If ENV had any honesty in their approach, they would allow comments so that this piece of junk gets the criticism it deserves

      Delete
    12. The erroneous post is still up. I realize it might take a while to write a revised version, but it only takes a moment to take the page down with a brief note that it is being retracted on account of errors. Instead, it stays up to mislead and misinform more people. Why is that, Jonathan?

      Delete
    13. ...and it's still up.

      Every minute that post is up, Jonathan, is another minute that you are lying to anyone who reads it. Does this not concern you? Even if you don't care about scientific ethics, don't you care about the part of your Holy Book that says "Thou shalt not bear false witness"?

      Delete
    14. Jonathan is now going about deleting facebook threads and blocking folk who point out his obvious deficiencies.
      Creationist dialogue at it's best

      Delete
    15. It must be tough for religious proselityzers who tie their apologetics to scientific claims. Scientific ethics demand that one state the truth, even if that contradicts your personal beliefs. However, if that truth refutes your religious claim, then it becomes blasphemy. So does one do? State the truth and blaspheme, or lie? I guess Jonathan has made his choice.

      Delete
    16. We have saved some of the threads he deleted.
      I've a feeling he's not heard the last of this attempt to censor and refuse to print retractions on pages that still contain the article.

      Delete
    17. Here is his idea of a "retraction" http://www.evolutionnews.org/2013/08/unitary_pseudog075831.html
      This bit in particular "I had consulted the Ensembl Genome Database regarding the GULO pseudogene in humans, and that database reported that it produces a transcript but no known protein product. Upon further investigation, however, I've discovered that the Ensembl database appears to be inaccurate on that point, and it's not confirmed that the GULO pseudogene produces a transcript (indeed, clicking on "Supporting evidence," one finds that there is "No Transcript supporting evidence for this transcript")"
      is a barefaced lie. He had to have it pointed out to him that there was no supporting evidence for this "transcript". Basically, he never read the supporting evidence bit.
      He also omitted to mention his failure to find the major flaws in the Andersson paper he cited. The funniest one of course being that he used it as evidence that humans may produce vitamin C, when there was already vitamin c in the diets. He did claim to have read this paper and said he thought it was fine. This was the first and only paper I checked. I dread to think what else I would have found. I'm glad I didn't put any extra effort in as he deleted the thread.
      Oh, and JM, if you are reading, we have copies of this thread should you wish to dispute this.

      Delete
    18. My favorite line from mclatchie's new article is:

      "I could go on in a similar vein for some time."

      Yeah, I'm sure he could. IDiot-creationists like mclatchie could go on and on and on with the same old dishonest, evasive, blame shifting, goal post moving, responsibility denying, self serving BS until the end of time, and will unscrupulously do so without hesitation.

      So much for mclatchie being "more interested in the truth".

      Delete
    19. LARRY: Do you agree that it's impossible?
      JONATHAN: Yes, I think it is extremely unlikely. And yes, I will be posting something to that effect.

      Here's "something to that effect" (emphasis added). Note that only the first sentence is supported by evidence. All the rest is the product of wishful thinking:

      ... it's not confirmed that the GULO pseudogene produces a transcript (indeed, clicking on "Supporting evidence," one finds that there is "No Transcript supporting evidence for this transcript"). Part of the reason for this is that the GULO pseudogene lacks a canonical promoter. However, that doesn't necessarily mean this pseudogene produces no RNA transcript. Many metazoan loci possess non-canonical promoters that, moreover, can be millions of base pairs upstream of annotated exon...

      While my original hypothesis is probably incorrect with respect to this particular pseudogene, it remains possible that the human GULO pseudogene yields RNAs that perform some other function in the cell...

      What I proposed might be happening in the GULO pseudogene could very well be happening in other unitary pseudogenes...

      Delete
    20. Self correction: "Note that only the first two sentences are supported by evidence."

      Delete
    21. By trying to save face, mclatchie has only shown that he has no integrity.

      On another note, while I was looking for some information about the diet of Tarsiers I came across this website, which some of you might find interesting:

      http://oolon.awardspace.com/SMOGGM.htm#scurvy

      (And there's more on their home page).

      Delete
    22. I looked around too, and I couldn't find out how tarsiers get their vitamins. Or guinea pigs, for that matter.

      Delete
    23. Non-frugivorous bats have the same problem, but OK, everyone knows bats are an exception to every rule.

      Delete
    24. At the risk of sounding stupid, how about this:

      Tarsiers apparently eat mostly insects, including moths and butterflies. It seems likely that they also eat the larvae (caterpillars) of moths and butterflies. Many moths and butterflies eat flower nectar and many caterpillars (and other insects) eat flowers. Nectar and the flowers themselves often (or always?) contain vitamins, including vitamin C.

      Picture a Tarsier eating an insect that has just filled up on nectar or a flower. The gut of the insect contains as yet undigested vitamins, including vitamin C. Tarsiers would eat many insects every day/night. A little bit of vitamin C in some or most of the insects may supply enough vitamin C for the Tarsiers. And what if a Tarsier eats a bat that has just eaten some nectar, fruit,or flowers?

      I haven't yet taken the time to see whether there are any nectar, fruit, or flower eating bats in Tarsier environments, so I'm just tossing out some speculative ideas. What do you guys think?


      Piotr asked:

      "Or can they do without it?"

      I don't know but maybe that's the case, and maybe the same thing is true for Guinea Pigs.

      I found another site that you guys might want to look at. The article is a few years old:

      http://high-fat-nutrition.blogspot.com/2010/02/ok-ascorbate-and-lpa.html

      Delete
    25. This interesting article was linked to in one of the comments on the high-fat-nutrition.blogspot.com site:

      http://ajcn.nutrition.org/content/27/3/310.full.pdf

      Delete
    26. "he whole truth claims,
      'At the risk of sounding stupid, how about this"
      When was the time when you didn't sound stupid?

      Delete
    27. @TWT: Bats are very odd in this respect. They show a whole range of transitional stages of loss of function (pseudogenisation) affecting GULO, and a few species apparently still synthesise Vitamin C. I wonder what IDiots would say to this:

      http://mbe.oxfordjournals.org/content/28/2/1025.full.pdf


      Apparently some insects (e.g. bees and some orthopterans and beetles) contain appreciable amounts of vitamin C.

      https://tspace.library.utoronto.ca/bitstream/1807/6678/1/jb06047.pdf

      Tarsiers are fond of crickets and grasshoppers -- perhaps they are able to extract enough ascorbic acid from their favourite species?

      Delete
    28. Piotr, apparently they must be able to extract enough ascorbic acid from their favorite species or from whatever else they eat, or they don't need vitamin C. I would think that it has to be one or the other, and I'm inclined to think that they do get enough vitamin C from their diet.

      Bats are just downright weird, but totally cool. A few years ago a friend of mine lived in a house in the woods and if he left the back door open some bats would come in and roost (upside down of course) on the walls of the utility room during the day. I could walk right up to them.

      Regarding Guinea Pigs, I just came across a site that says:

      "Wild guinea pigs enjoy vegetarian diets. They enjoy feasting on leaves, hay, grass, and even flowers. Clovers are a special treat to the guinea pig's palate."

      From here:

      http://animals.pawnation.com/guinea-pigs-life-wild-4154.html

      If they eat flowers, that could explain how they get vitamin C, assuming that the flowers they eat contain Vitamin C.

      Delete
    29. A lot of websites claim that Guinea Pigs do need vitamin C in their diet to prevent scurvy, so if that's the case the wild ones must be getting vitamin C from what they eat.

      I haven't had time yet to search for any in-depth studies of wild Guinea Pigs. I did find something amusing though:

      "Folk doctors in the Andes use guinea pigs to detect illness in people. They believe that when the rodent is pressed up against a sick person, it will squeak when near the source of disease."

      Delete
    30. Piotr, I just took a quick look at the papers you linked to (thanks for the links!). It's nice to find out that some insects do contain appreciable amounts of vitamin C and other vitamins "even when dried".

      And the differences in bats when it comes to synthesizing vitamin C are very interesting.

      Delete
  7. I will simply quote the comment from Area Man at PZ Myers' blog: "Why not just declare that the GLUO gene was perfectly functional at the creation, but was rendered dysfunctional due to all the delicious citrus fruit in the garden of Eden + the super high mutation rate during the Flood?"

    I mean, it works for all the other BS they need it to, why not this one?

    ReplyDelete
    Replies
    1. I also thought that God may have left us a decaying pseudogene as a molecular reminder of Original Sin.

      Because ye like this fruit so much, ye shall have to eat of it all the days of your lives, or the LORD will smite you with the scurvy; for your GULO shall be broken in you, and in your children, and the children of your children.

      But what did all the other haplorrhines (apes, Old World monkeys, and tarsiers) do to deserve it?

      Delete
    2. No, that makes perfect sense. Frugivory is the original sin, so we can place the actual position of Adam and Eve not, as everyone thinks, at the origin of H. sapiens, but at the origin of haplorrhine primates.

      But whatever did the poor guinea pigs do?

      Delete
    3. While we are at it, tarsiers are pure carnivores, aren't they? Whatever their original sin, how do they get their vitamin C? Or can they do without it?

      Delete
    4. John asked:

      "But whatever did the poor guinea pigs do?"

      yhwh is a jealous god, and Guinea Pigs are just so damn cute and cuddly, so they have to be punished for it. ;)

      Delete
  8. Now there's a slight problem with this scenario since RNA editing requires RNA

    Really?

    ReplyDelete