Sunday, August 23, 2015

How do Intelligent Design Creationists deal with pseudogenes and false claims?

Some of the people who comment here have pointed out that this is the second anniversary of a post by Jonathan McLatchie on Evolution News & Views (sic): A Simple Proposed Model For Function of the Human Vitamin C GULO Pseudogene.

That post is significant for several reasons. Let's review a bit of background.

Intelligent Design Creationists have a problem with pseudogenes. Recall that pseudogenes are stretches of DNA that resemble a gene but they appear to be non-functional because they have acquired disruptive mutations, or because they were never functional to begin with (e.g. processed pseudogenes). All genomes contain pseudogenes. The human genome has more than 15,000 recognizable pseudogenes.1 This is not what you would expect from an intelligent designer so the ID crowd tries to rationalize the existence of pseudogenes by proposing that they have an unknown function.

Jonathan Wells devoted a chapter and an appendix to pseudogenes in his book The Myth of Junk DNA. The chapter title was: Pseduogenes—Not so Pseudo After All. I reviewed that section and showed that the argument for the fucntion of pseudogenes was nonsensical [Junk & Jonathan: Part 8—Chapter 5].2 McLatchie revived the argument by proposing the the GULOP (GULO) pseudogene could, in fact, be active.

For a description of this pseudogene see: Human GULOP Pseudogene. It's the remnant of a gene that used to encode the enzyme L-glucono-γ-lactone oxidase, one of the key enzymes in the pathway to vitamin C. Unlike most mammals, humans and other primates are unable to synthesize vitamin C on their own and have to acquire if from food.3 Here's a diagram showing the gene fragment in the human genome compared to the intact gene in the rat genome.


Note that the fragment in our genome lacks a promoter and seven of the 12 exons in the intact gene.

McLathie proposed that the human GULOP sequence could produce a functional enzyme through editing of the RNA transcript. It was part of a general argument that pseudogenes could be functional because stop codons and small deletions in the DNA sequence could be altered post-transcriptionally by RNA editing.

Here's the important part. I criticized McLathie's argument by pointing out the obvious: (1) the human DNA sequence isn't transcribed, (2) the pseudogene is missing seven exons making it somewhat difficult to recreate a functional mRNA by RNA editing [How IDiots Would Activate the GULOP Pseudogene]. McLatchie responded by admitting that he was wrong: Unitary Pseudogenes and RNA Editing.

That was pretty amazing. You will note that the original post now has an update4 at the top of the post stating ...
Update: Please see the article available at this link for an important correction and revision to the argument entertained here.
Not unexpectedly, the mea culpa was accompanied by a good deal of rationalization explaining why he (McLatchie) had made a honest mistake.5 Not only that, the RNA editing argument still could apply to lots of other pseudogenes even though it doesn't work for GULOP [see: What Happens When a Creationist Argument Is Refuted?].

The most important lesson in this little episode is that some Intelligent Design Creationists are serious about debating their ideas and they will respond to scientific criticism. That's encouraging. It's why I think we should continue to refute and debate the scientific claims of Intelligent Design Creationists even though most of the time it seems pointless.


1. Pseudogenes evolve over time by random genetic drift and fixation of neutral mutations. After about 100 million years, they can no longer be recognized as pseudogenes because their sequences are indistinguishable from other forms of junk DNA.

2. Shocking, isn't it?

3. That's why we get scurvy.

4. It's a bit disingenuous to link to an "update" instead of stating clearly that the original post is completely wrong.

5. It was the fault of the Ensembl Genome Database for not making it clear that the DNA sequence wasn't transcribed and for presumably not making it clear that seven exons were missing. McLatchie also "forgot" to mention that he learned of his error by reading my blog post. We knows that's the case because he commented on my post and admitted he was wrong.

37 comments :

  1. It was the fault of the Ensembl Genome Database for not making it clear that the DNA sequence wasn't transcribed and for presumably not making it clear that seven exons were missing. McLatchie also "forgot" to mention that he learned of his error by reading my blog post. We knows that's the case because he commented on my post and admitted he was wrong.

    The information was available on the Ensembl data base, but not in a way that McLatchie could understand. For some reason, the data base was constructed in such a way that people who did not have the first fucking clue about how to use it, and had not bothered to learn, might not be able to understand the results they obtained. Go figure.

    In addition to "forgetting" to credit Sandwalk for pointing out his error, he also did not mention the several commentators on his Facebook page who advised him on how to interpret Ensembl and brought to his attention the fact that the pseudogene is not transcribed. He did, however, take the steps of banning all the people who had helped him in this way and deleting all their comments. The discussion has, fortunately, been archived here:

    https://www.facebook.com/groups/151405404861/10151664876239862/?hc_location=ufi

    This behavior is all very puzzling from someone who claims to be a scientist interested in the honest and objective pursuit of the truth. It is, however, not puzzling at all if Jonathan McLatchie is really nothing more than a liar.

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    1. The original post carries no disclaimer, in red, saying RETRACTED BY THE AUTHOR. Those who follow the added link and bother to read the "update" will not learn that McLatchie was dead wrong. They'll find out that he'd been misled by "errors" in the ENSEMBL database, so his hypothesis, while it may still be correct in general, does not quite work in the specific case of human GULOP. And of course cdesign proponentsits continue to use McLatchie's "research" to prove that pseudogenes aren't really pseudo.

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  2. Only a few days ago I was linked yet again to McLatchie's first GULOP post by a cdesignproponentsist as evidence of function. His half-hearted and dishonest retraction is often claimed to not be an actual retraction and scientists are accused of "spinning" it as such.

    It's one thing to make an honest mistake and publish an erroneous article. It's quite another to then leave that article out there.

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    1. See, that's the problem. If McLatchie was writing for people with the ability and inclination to actually understand the things they read on evolutionary theory, then maybe his rectraction, mealy-mouthed and vague though it is, might be understood. But he's writing for creationists. If he was to scrawl in giant red letters "Me wrong. Sorry." it still wouldn't get thru to most of them.

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  3. Over at Uncommon Descent, "News" (Denyse O'Leary) endlessly trumpets the rising number of retractions in science. Not-so-subtle subtext: see, you can't trust science.

    Somehow she hasn't mentioned McClatchie's retraction.

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    1. And she does that at the same time that she claims a grand conspiracy exists in the scientific establishment to suppress contradictory evidence. Ms. O'Leary is blissfully immune to cognitive dissonance.

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    2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145266/

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    3. Mr. Mind:

      please educate all the %$#@*here how and why an organism loses the ability to metabolize vitamin C, then reactivates it and then lose it again and possibly reactivates again

      First you have to establish that this event actually occurred, or at least give some reference to the claim. I think you might have been confused by a sentence quoted from a paper on GULO in bats, where you have misinterpreted the statement that it had been re-activated twice to be that it had happened twice in succession in a single lineage, rather than twice in separate species whose ancestors had lost it.

      As for how regain of function can happen, there is some evidence that multiple bat lineages lost that function independently and recently, so that few mutations would be required to regain function, something that could happen through neutral evolution.

      http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0027114

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    4. Another thing Skeptical Mind needs to do, besides read a little, is to drop the way of thinking that leads him to write "an organism". Because no one on the science side said "an" organism did such.

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    5. Whoops, he's gone already. Larry, is it your policy to kill his posts as soon as they appear, or are you killing only certain posts? If the latter, what criteria are you using?

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    6. @John Harshman

      I'm deleting almost all of his posts because of his attitude. He doesn't contribute anything to the discussion.

      Believe it or not, I don't check the comments every hour so some of his comments may survive for a bit. At some point the rest of you are going to catch on and realize that responding to him is a waste of time.

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    7. Professor, His comments and the responses might be more valuable than you'd imagine. Some dummies like myself actually learn from the exchange once in a while.

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    8. Cut out the middle loony. Ask a question yourself every so often. Simpler.

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    9. A key sentence from the article Allopatrik cited above:

      Therefore, reactivation likely only requires mutations in sites involved in the regulation of the expression of these genes.

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    10. The context of the sentence I quoted above is reactivation of the GULO gene in some bats.

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  4. I promise that I will not delete any comments that contain reasonable questions and resonable discussion of the issues unless they contain vulgar insults. The only exception is comments from people who have been banned.

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  5. Larry

    "I promise that I will not delete any comments that contain reasonable questions and resonable discussion of the issues unless they contain vulgar insults. The only exception is comments from people who have been banned."

    Really?

    Well, is the rat GULOP gene and human GULPO "pseudogene" a fair comparison in your view? I know it is going to be a "yes" so why don't you elaborate on the strengths of your argument, and I will elaborate on mine. I surly hope you don't change your mind now.

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    1. What do you mean by "a fair comparison"? How are we intended to compare them and for what purpose? What argument are you expecting Larry to elaborate on? More important, what is your argument and how do you intend to support it? So far as I can tell, you have yet to make one.

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    2. You surely have them if you fail to see that the "P" in "GULOP" stands for "pseudogene". Rats have a GULO gene, humans have the homologous GULOP(seudo)gene.

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    3. Well, is the rat GULOP gene and human GULPO "pseudogene" a fair comparison in your view?

      That's actually not a bad question, Sceptical. Maybe you should ask it of your fellow creationist blockhead John McLatchie. How did he figure what parts of the human GULOP gene needed to be restored in order for it to be rendered functional again? Ask him, and let us know what he says....

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    4. As usual, SM fails to answer questions. Since he fails to clarify, I will throw words. The rat GULO was used as an example of a functional GULO gene. It's similar to other functional mammalian GULO genes. For example, they all have the same exon/intron pattern. It would have been reasonable to use a lemur instead, but the rat should do for most purposes. I believe I may have mentioned the UCSC genome browser before. You should search for GULO in it and you will find comparisons of a variety of mammalian GULO regions in one of the tracks.

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    5. Let me spell it out for you, Mind. Rats have no GULOP because their gene is fully functional, that is, not a pseudogene. Strictly speaking, "pseudo" after GULOP is redundant (like, say "PIN number" or "ATM machine"), but I'm not enough of a pedant to object to it. Now, concentrate again for a moment and try to remeber:

      GULO is short for the gene encoding L-gulono-γ-lactone oxidase. No "P" if the gene is functional.

      GULOP is the corresponding pseudogene in those species whose GULO gene has been inactivated by disabling mutations. The human GULOP contains anly a fraction of the original GULO sequence. Several exons have been completely deleted.

      I don't know if the comparison is "fair", but it's certainly meaningful. It demonstrates that the rat's GULO and our GULOP are homologous (come from a common ancestor). The sequence of the human pseudogene can't be explained by its functionality (it has none today) but is fully explained by its evolutionary history (original function, lost tens of millions years ago + neutral decay in the absence of selective constraints).

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    6. John H

      My question was: Is the comparison of human GULO "pseudo" gene and rat GULO gene scientifically acceptable considering all the details involved?

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    7. Larry

      Why don't you get involved much in subjects you initiate? I find this very unusual with a man who has so much passion for his beliefs.

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    8. SM:

      I believe I answered that question. Yes, it's acceptable. Why wouldn't it be? Again, you can compare GULO regions from a variety of mammal species. The ones with functional GULO look like the rat's, while the primates with GULO pseudogenes look more like the human. Bats are an interesting case, in which deactivation happened comparatively recently, and they still retain all the exons. You need to stop doing your research exclusively on creationist web sites.

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  6. So here are some facts about the GULO "pseudo" gene that supposedly proves that humans inherited this gene in the process of evolution.

    "The Human GULO Pseudogene—Evidence for Evolutionary Discontinuity and Genetic Entropy

    Modern genomics provides the ability to screen the DNA of a wide variety of organisms to scrutinize broken metabolic pathways. This wealth of data has revealed wide-spread genetic entropy in human and other genomes. Loss of the vitamin C pathway due to deletions in the GULO (L-gulonolactone oxidase) gene has been detected in humans, apes, guinea pigs, bats, mice, rats, pigs, and passerine birds. Contrary to the popularized claims of some evolutionists and neo-creationists, patterns of GULO degradation are taxonomically restricted and fail to support macroevolution. Current research and data reported here show that multiple GULO exon losses in human, chimpanzee, and gorilla occurred independently in each taxon and are associated with regions containing a wide variety of transposable element fragments. Thus, they are another example of sequence deletions occurring via unequal recombination associated with transposable element repeats. The 28,800 base human GULO region is only 84% and 87% identical compared to chimpanzee and gorilla, respectively. The 13,000 bases preceding the human GULO gene, which corresponds to the putative area of loss for at least two major exons, is only 68% and 73% identical to chimpanzee and gorilla, respectively. These DNA similarities are inconsistent with predictions of the common ancestry paradigm. Further, gorilla is considerably more similar to human in this region than chimpanzee—negating the inferred order of phylogeny. Taxonomically restricted gene degradation events are emerging as a common theme associated with genetic entropy and systematic discontinuity, not macroevolution."

    I will provide links and more genomic comparison facts after I reboot my computer.

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    1. This is taken from https://answersingenesis.org/genetics/human-gulo-pseudogene-evidence-evolutionary-discontinuity-and-genetic-entropy/

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    2. So here are some facts...

      So you still think Tomkins spurious numbers and misrepresentations are "facts"? These creationist canards are harder to kill than Grigori Rasputin.

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    5. OK, at this point I see no reason why this retard shouldn't be banned for good

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    6. NO EVIDENCE IN THE WORLD WILL CONVINCE SOMEONE TO CHANGE HIS/HER MIND IF THEY DON'T WANT TO DO IT. I KNOW IT IS SAD BUT THIS IS A FACT.

      This is a scientific fact. I can prove it many times over.


      Yes, I agree you prove it every time you repeat the same lie, fallacy or creationist misrepresentation for the hundredth time, as though you'd never seen it refuted. Are you a natural, or did you have to learn it?

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  7. See this as a hypothesis for the role of transcribed pseudogenes:

    https://en.wikipedia.org/wiki/Competing_endogenous_RNA_(CeRNA)

    "Recent studies have shown that the interaction of the miRNA seed region with mRNA is not unidirectional, but that the pool of mRNAs, transcribed pseudogenes, long noncoding RNAs (lncRNA),[4] circular RNA (circRNA) [5][6] compete for the same pool of miRNA.[7] These competitive endogenous RNAs (ceRNAs) act as molecular sponges for a microRNA through their miRNA binding sites (also referred to as miRNA response elements, MRE), thereby de-repressing all target genes of the respective miRNA family"

    Many pseudogenes may be expressed than previously thought since many of them may only be expressed in tissue, developmental, and cell specific contexts.

    Now what project actually tracks those kinds of expression. Hmm....uh...ENCODE. That's right ENCODE rather than the enclave of evolutionary biologists devoted to the promotion of worthless evolutionary ideology over advancement of medical science.

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    1. Transcribed =/= functional.

      Also, please try to determine the fraction of all pseudogenes which are transcribed, and then determine their transcription level. Without these numbers, your handwaving towards the mere expression of some pseudogones, does nothing to alter the evidence that most pseudogenes are in fact junk.

      How many are expressed out of how many there are in total and just as importantly, how expressed are they? What evidence do you have to show that we aren't just seeing pervasive transcription?

      You never bring us these numbers, you just handwave at titles.

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    2. Sal's religious fanaticism causes him to ignore the crucial question of *relative transcription levels* which invalidates hish imaginative speculations on hypothetical functions for pseudogenes, because the speculative mechanisms are not plausible-- much less supported by evidence.

      We have complained, over and over, that many ENCODE "transcripts" from non-coding regions have very low expression levels, like 1 transcript per cell. This kills the speculative mechanisms.

      If your speculative mechanism involves one RNA "P" specifically binding another RNA "Q", etc. to ultimately reduce and thus regulate translation of a final protein product, and if there are 10,000 Q's per cell, but only one R, then your proposed "regulatory" function reduces the number of Q's from 10,000 to 9,999. This "regulatory function" is not large enough to be detectable by natural selection in the wild or in lab assays.

      We've pointed this out many times.

      As speculation, it's implausible. There's also the lack of evidence problem you have.

      But Sal insists we must assume 100% functional DNA by default unless we can prove a negative. So "heads I win, because I define myself to win."

      That's not what we were told two years ago when ENCODE came out. Two years ago, the ID proponents told us that they now had all the evidence to prove all DNA was functional. But *now* the ID proponents mewl that their "evidence" is, we must *assume* all DNA is functional a priori until proven otherwise. ENCODE was a waste of $300 million then, huh?

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