Tuesday, November 16, 2010

I Get A Kick Out Of Endogenous Retroviruses

I've mentioned it before. That dreaded 29+ Evidences for Macroevolution by Dr. Douglas Theobald. I took the time to examine what has been pontificated as the "smoking-gun evidence for evolution" and the "irrefutable evidence." What many Darwinians believe is the most irrefutable argument for their views is the evidence from endogenous retrovirus insertion sites. I am petrified of this evidence. In fact, I am biting my nails. After gathering a few facts, I sent the following email to Dr. Douglas Theobald, concerning this astounding piece of evidence:


 Dear Dr. Douglas Theobald,

In your 2004 article “29+ Evidences for Macroevolution” you write (Part 4: The Molecular Sequence Evidence, Prediction 4.5: Molecular evidence - Endogenous retroviruses):
   “Endogenous retroviruses provide yet another example of molecular sequence evidence for universal common descent.”

You then go on to propose how this molecular sequence evidence for universal common descent could be potentially falsified:
      “It would make no sense, macroevolutionarily, if certain other mammals (e.g. dogs, cows, platypi, etc.), had these same retrogenes in the exact same chromosomal locations. For instance, it would be incredibly unlikely for dogs to also carry the three HERV-K insertions that are unique to humans, as shown in the upper right of Figure 4.4.1, since none of the other primates have these retroviral sequences.”

       Consider this molecular sequence evidence for universal common descent falsified. Essentially, in order to falsify this evidence, we must find an outgroup species that shares with a species of a certain clade the same retrogene or retrogenes insertions, but these insertion sites are not shared by the other species of that clade. This is what it boils down to.
    Interestingly enough, Barbulescu et al. (2001) have identified “a human endogenous retrovirus K (HERV-K) provirus that is present at the orthologous position in the gorilla and chimpanzee genomes, but not in the human genome.”

What we have here is an outgroup species (gorilla) that shares a retrogene insertion site with a species (chimpanzee) of a certain clade (human-chimpanzee clade), but this insertion site is not shared by the other species of that clade. This alone, by your own criteria, falsifies the retrogene evidence for universal common descent you advance in your article.
    
      Similarly, Bonner et al. (1982) report that the endogenous retrovirus colobus type C virus CPC-1 is shared by the chimpanzee and the gorilla but it is absent from the human genome.
Also note that certain classes of type C retroviruses are found in wooly monkeys and the gibbon ape, but it is not found in African great apes [Lieber et al. 1975].

     Humans and Asian apes lack PTERV1 retroviruses, but they are present in African great apes and Old World monkeys [Yohn et al. 2005].

  To quote Yohn et al. 2005:
“For example, only one interval is shared by gorilla and chimpanzee; however, two intervals are shared by gorilla and baboon; while three intervals are apparently shared by macaque and chimpanzee.…If these sites were truly orthologous and, thus, ancestral in the human/ape ancestor, it would require that at least six of these sites were deleted in the human lineage. Moreover, the same exact six sites would also have had to have been deleted in the orangutan lineage if the generally accepted phylogeny is correct. Such a series of independent deletion events at the same precise locations in the genome is unlikely.”


In summary, the very criteria that you stated would falsify this evidence for universal common descent has been met, and hence this evidence is effectively falsified. I am writing you so that you might add a correction to your article and realize that this evidence has been falsified.

Respectfully,
Livingstone Morford

References:

Barbulescu M, Turner G, Su M, Kim R, Jensen-Seaman MI, Deinard AS, Kidd KK, Lenz J. A HERV-K provirus in chimpanzees, bonobos and gorillas, but not humans. Curr. Biol. 11(10):779-83 (2001).

Bonner TI, Birkenmeier EH, Gonda MA, Mark GE, Searfoss GH, et al. Molecular cloning of a family of retroviral sequences found in chimpanzee but not human DNA. J. Virol. 43: 914–924 (1982).

Lieber MM, Sherr CJ, Todaro GJ, Benveniste RE, Callahan R, et al. Isolation from the Asian mouse Mus caroli of an endogenous type C virus related to infectious primate type C viruses. Proc. Natl. Acad. Sci., 72: 2315–2319 (1975).

Yohn CT, et al. Lineage-specific expansions of retroviral insertions within the genomes of African great apes but not humans and orangutans. PLoS Biol, 3:110 (2005).


There. Now I've gotten this load off my chest. That's some absolutely amazing piece of evidence.



32 comments:

  1. Thanks John.
    I sent Dr. Douglas Theobald this email on the 16th of November, and he has yet to reply. Something tells me that he'll never reply...

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  2. "“a human endogenous retrovirus K (HERV-K) provirus that is present at the orthologous position in the gorilla and chimpanzee genomes, but not in the human genome.”"
    -"…This leads to the conclusion that, for some fraction of the genome, the gorilla and chimpanzee genomes are more closely related to each other than either is to humans...
    Genetic studies indicated that humans and chimpanzees are the most closely related pair for much of the genome [1–4]. However, for some fraction of the genome, they are not [1, 3, 4]. Such data are consistent with a model in which alleles segregated differently among the three eventual lineages [1, 4, 19–21]."

    "CPC-1 is shared by the chimpanzee and the gorilla but it is absent from the human genome."
    -and do they report whether they are indeed orthologous and in the same positions with the same direct repeats?

    "To quote Yohn et al. 2005:"
    "insertions occur at non-orthologous regions between closely related species... data are consistent with a retroviral infection that bombarded the genomes of chimpanzees and gorillas independently and concurrently"

    "Also, your post may be further refuted by pointing out that there is gathering evidence that ERV insertions are not random"
    -the integration reaction has no sequence specificity.

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  3. Its no wonder he didn't reply: you didn't even bother to read the papers but rather, I suspect, mindlessly parroted creationist propaganda who misquote scientific papers.

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  4. Oh don't worry, Dr. Morford will reply.

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  5. A brief comment before I begin a general evisceration of your response. It would be helpful if you cited the papers you quote, so I can see what paper you’re referring to.
    That said, I will begin by quoting your response, section at a time.

    “This leads to the conclusion that, for some fraction of the genome, the gorilla and chimpanzee genomes are more closely related to each other than either is to humans...”

    Fantastic. Except that there’s one small problem with your response. Namely, that you are forgetting Dr. Douglas Theobald’s criteria for falsifying the retrogene evidence for common descent.
    Maybe you didn’t read the entirety of my blog post, so I will quote the relevant sections:
    “It would make no sense, macroevolutionarily, if certain other mammals…had these same retrogenes in the exact same chromosomal locations. For instance, it would be incredibly unlikely for dogs to also carry the three HERV-K insertions that are unique to humans…since none of the other primates have these retroviral sequences.” – Dr. Douglas Theobald’s criteria for falsification.

    This, in turn, leads us to:
    “Essentially, in order to falsify this evidence, we must find an outgroup species that shares with a species of a certain clade the same retrogene or retrogenes insertions, but these insertion sites are not shared by the other species of that clade. This is what it boils down to.”

    This scenario is exactly what Barbulescu et al. (2001) have detailed. So, the argument that ‘for some fraction of the genome, the gorilla and chimpanzee genomes are more closely related to each other than either is to humans...’ holds little water when we examine it in the light of falsification.

    “insertions occur at non-orthologous regions between closely related species... data are consistent with a retroviral infection that bombarded the genomes of chimpanzees and gorillas independently and concurrently…”

    This would be a lovely argument, were it not for the problem that you’re not refuting the original quote of Yohn et al. Instead, you are quoting the Abstract of the paper, without having read the actual paper for yourself. In short, you are quoting an irrelevant portion of the paper. Care to respond to my original quote:
    ““For example, only one interval is shared by gorilla and chimpanzee; however, two intervals are shared by gorilla and baboon; while three intervals are apparently shared by macaque and chimpanzee.…If these sites were truly orthologous and, thus, ancestral in the human/ape ancestor, it would require that at least six of these sites were deleted in the human lineage. Moreover, the same exact six sites would also have had to have been deleted in the orangutan lineage if the generally accepted phylogeny is correct. Such a series of independent deletion events at the same precise locations in the genome is unlikely.”

    While you quoted an irrelevant portion of the Abstract, I’m quoting this from their Results. So, what you do is scan over the abstract, pick up something that you think sounds neat, and then respond with that, ignoring the fact that it’s not refuting the my far more relevant quotation.

    References:

    Bonner TI, Birkenmeier EH, Gonda MA, Mark GE, Searfoss GH, et al. Molecular cloning of a family of retroviral sequences found in chimpanzee but not human DNA. J. Virol. 43: 914–924 (1982).

    Yohn CT, et al. Lineage-specific expansions of retroviral insertions within the genomes of African great apes but not humans and orangutans. PLoS Biol, 3:110 (2005).

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  6. "Its no wonder he didn't reply: you didn't even bother to read the papers but rather, I suspect, mindlessly parroted creationist propaganda who misquote scientific papers."

    For the record, and contrary to popular opinion, I actually do have a life.
    To my knowledge, I am the only one who has brought up Yohn et al.'s paper.

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  7. "the integration reaction has no sequence specificity."

    See:

    Relationship between retroviral DNA-integration-site selection and host cell transcription(PNAS February 1, 2005 vol. 102 no. 5 1436-1441).

    "Retroviral DNA integration occurs throughout the genome; however, local “hot spots” exist where a strong preference for certain sites over others are seen, and more global preferences associated with genes have been reported. "

    Integration site selection by retroviruses (AIDS Rev. 2004 Jan-Mar;6(1):13-21.).

    "Integration is not sequence specific, thus all chromosomal sites could potentially host integration events. However, this is not what is observed in vivo, where integrated viruses are preferentially detected in chromatin regions characterized by an open structure, a hallmark of actively transcribed genes."


    Retroviral DNA integration: ASLV, HIV, and MLV show distinct target site preferences (PLoS Biol. 2004 Aug;2(8):E234. Epub 2004 Aug 17.).

    "ASLV vectors showed only a weak preference for active genes and no preference for transcription start regions. Thus, each of the three retroviruses studied showed unique integration site preferences, suggesting that virus-specific binding of integration complexes to chromatin features likely guides site selection."

    Retroviral DNA integration: viral and cellular determinants of target-site selection (PLoS Pathog. 2006 Jun;2(6):e60. Epub 2006 Jun 23.).

    "Retroviruses differ in their preferences for sites for viral DNA integration in the chromosomes of infected cells. Human immunodeficiency virus (HIV) integrates preferentially within active transcription units, whereas murine leukemia virus (MLV) integrates preferentially near transcription start sites and CpG islands."


    Molecular genetics and target site specificity of retroviral integration (Adv Genet. 2001;43:33-69).

    "The mechanism by which integration sites are chosen is not well understood, and is influenced by several factors, including DNA sequence and structure, DNA-binding proteins, DNA methylation, and transcription. Integrase, the viral enzyme responsible for catalyzing integration, also plays a key role in controlling the choice of target sites."


    Does that satisfy you?

    P.S. Thanks for following my blog.

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  8. Its no wonder he didn't reply: you didn't even bother to read the papers but rather, I suspect, mindlessly parroted evolutionist propaganda who misquote scientific papers.

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  9. I love what you just said John - truly brilliant ; )

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  10. It would be helpful if you cited the papers you quote"
    -each of your quotes taken from papers is quoted by me and underneath is a reply from the same paper

    "Fantastic. Except that there’s one small problem with your response. Namely, that you are forgetting Dr. Douglas Theobald’s criteria for falsifying the retrogene evidence for common descent."
    -oh no science making progress and finding exceptions to rules, we cant have that! back to the dark ages! :(

    "This scenario is exactly what Barbulescu et al. (2001) have detailed."
    -and an explanation is given, which you decided to ignore. ignorance is also a mark of the dark ages :(

    "Instead, you are quoting the Abstract of the paper, without having read the actual paper for yourself"
    -in fact i read the whole paper, but found that the abstract already summed up what i needed to say.

    "n short, you are quoting an irrelevant portion of the paper"
    -actually, it deals with the "problem" you are suggesting is there but isnt.

    "Care to respond to my original quote:"
    -no, i already have.

    "I’m quoting this from their Results"
    -mmhmm do you know about the fallacy of quoting out of context? i take it that you are a creationist so i expect you do not.
    http://en.wikipedia.org/wiki/Fallacy_of_quoting_out_of_context

    "Thank you, Livy, for the detail work you have done for us. Blessings."
    -yes, let us herald in the dark ages of ignorance and fallacies

    ""the integration reaction has no sequence specificity."
    See:"
    -lovely, any sequence specificity there?

    "Does that satisfy you?"
    -no, i dont think you know what a sequence is, or what it means to have specificity.

    "Its no wonder he didn't reply: you didn't even bother to read the papers but rather, I suspect, mindlessly parroted evolutionist propaganda who misquote scientific papers. "
    -mmhmm this seems a bit rich, if not ironic. funny indeed.

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  11. "It would be helpful if you cited the papers you quote"
    -each of your quotes taken from papers is quoted by me and underneath is a reply from the same paper

    "Fantastic. Except that there’s one small problem with your response. Namely, that you are forgetting Dr. Douglas Theobald’s criteria for falsifying the retrogene evidence for common descent."
    -oh no science making progress and finding exceptions to rules, we cant have that! back to the dark ages! :(

    "This scenario is exactly what Barbulescu et al. (2001) have detailed."
    -and an explanation is given, which you decided to ignore. ignorance is also a mark of the dark ages :(

    "Instead, you are quoting the Abstract of the paper, without having read the actual paper for yourself"
    -in fact i read the whole paper, but found that the abstract already summed up what i needed to say.

    "n short, you are quoting an irrelevant portion of the paper"
    -actually, it deals with the "problem" you are suggesting is there but isnt.

    "Care to respond to my original quote:"
    -no, i already have.

    "I’m quoting this from their Results"
    -mmhmm do you know about the fallacy of quoting out of context? i take it that you are a creationist so i expect you do not.
    http://en.wikipedia.org/wiki/Fallacy_of_quoting_out_of_context

    "Thank you, Livy, for the detail work you have done for us. Blessings."
    -yes, let us herald in the dark ages of ignorance and fallacies

    ""the integration reaction has no sequence specificity."
    See:"
    -lovely, any sequence specificity there?

    "Does that satisfy you?"
    -no, i dont think you know what a sequence is, or what it means to have specificity.

    "Its no wonder he didn't reply: "
    -i find this quite rich if not ironic. funny indeed.

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  12. Is it just me or are Icsou1's responses making no sense? Hopefully he didn't go retarded on us.

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  13. That's a new one. Never had someone resort to stupidity as a defense.

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  14. "Is it just me or are Icsou1's responses making no sense?"
    -its just you.

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  15. With all due respect, your response places the meaning of the word ‘nonsense’ to a new level. If this is what you call a rebuttal, then I can only imagine what a mere cursory debunking would look like.

    oh no science making progress and finding exceptions to rules, we cant have that! back to the dark ages!

    Take that in with Dr. Douglas Theobald. He clearly articulated the criteria for falsifying the retrogene evidence for common descent: this criteria has been met, and hence by his stated criteria, the retrogene evidence for common descent is falsified. If that doesn’t suit you, that’s your problem. Inevitably, the phrase ‘moving the goal posts’ comes to mind. Furthermore, what do you say would falsify this evidence? This should be rather interesting.
    Your remark “back to the dark ages” is completely irrelevant. We are not discussing history – we are discussing whether or not the retrogene evidence for common descent has been falsified. If you want to discuss history, I’m sure there are many blogs out there that would love to hear your thoughts on history.

    …and an explanation is given, which you decided to ignore…

    I did not ignore the explanation. The explanation is simply not pertinent, because waving a magic wand and explaining away discrepancies in endogenous retrovirus phylogenies does not mean that Dr. Douglas Theobald’s stated criteria for falsification has not been met. It has been, and this is what Barbulescu et al. (2001) have demonstrated. You could come up with all the explanations you wanted to, but the observation would remain: the criteria has been met, and this evidence has therefore been falsified.

    i dont think you know what a sequence is…

    Really?

    what it means to have specificity…

    It really is too bad that you didn’t elaborate on this point. I suspect that you are the one who does not know what it means to have specificity. Next time you might want to refute what I actually posted instead of making short, trivial, and amusing remarks.

    its just you…

    I beg to differ.

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  16. Have fun Morgan. This guy's comments will become more stupid with each response.

    In my experience, it seems to be a tactic of his to act stupid when he realizes there are no supporting facts in favor of his argument. He does it all the time in order cover his rectal orifice.

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  17. "With all due respect, your response places the meaning of the word ‘nonsense’ to a new level"
    -im sorry, ad hominem doesnt count as an argument, or distract any (thinking) person away from your refuted claims.

    "He clearly articulated the criteria for falsifying the retrogene evidence for common descent"
    -citing old, informal references in favour of newer references which detail the 'problem' and evidence based solutions to it, is how a creationist would do science.

    "The explanation is simply not pertinent"
    -right because it doesnt suite your agenda.

    "It really is too bad that you didn’t elaborate on this point. I suspect that you are the one who does not know what it means to have specificity."
    -dont blame me for your downfall above.

    "In my experience, it seems to be a tactic of his to act stupid when he realizes there are no supporting facts in favor of his argument."
    -you obviously cannot read.

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  18. obviously you have nothing of value to add john, and are nothing more than a troll going against the rules set by the owner of this blog.

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  19. "obviously you have nothing of value to add john,"

    Nothing of value to you.

    "nothing more than a troll going against the rules set by the owner of this blog."

    Can you substantiate your claim?

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  20. "Nothing of value to you. "
    -so nothing of value to add to the topic? alright then.

    Post 1 - Debate and civil discourse is encouraged, but keep it civil. Moreover, I have no sympathy for trolls and they will be dealt with appropriately.

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  21. Sigh. It's 1:20 in the morning here, and I was planning to reply to this stuff n' nonsense today. That will have to wait though.

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  22. "-so nothing of value to add to the topic? alright then."

    Did I say that?

    "Debate and civil discourse is encouraged, but keep it civil.

    Yes. Okay.

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  23. "citing old, informal references in favour of newer references which detail the 'problem' and evidence based solutions to it, is how a creationist would do science."

    That's typical of the goal-post-moving Darwinians. Please elaborate how the ERV argument would be falsified by your standards.

    "-right because it doesnt suite your agenda."

    No, it's because regardless of Darwinian hand-waving, the criteria outlined by Dr. Theobald has been satisfied, and therefore the argument falsified.

    "-dont blame me for your downfall above."

    Um, that's not a refutation.

    "-you obviously cannot read. "

    Okay. Does this sound familiar:
    -im sorry, ad hominem doesnt count as an argument, or distract any (thinking) person away from your refuted claims.

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  24. Dr. Morford will win a Nobel Prize someday in biolgy or biochemistry. Heck maybe even ID if that's possible. Great article Livingstone and well written with many good points btw.

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  25. "Please elaborate how the ERV argument would be falsified by your standards."
    -if there were an ERV not shared by two closely related species, but between one of them and an out-group. that said, we all know science has no set rules. we know that, "for some fraction of the genome, the gorilla and chimpanzee genomes are more closely related to each other than either is to humans"

    "No, it's because regardless of Darwinian hand-waving, the criteria outlined "
    -see the above comment related to no strict rules in science, which comes hand in hand with the advancement of knowledge.

    "Okay. Does this sound familiar:
    -im sorry, ad hominem doesnt count as an argument, or distract any (thinking) person away from your refuted claims. "
    -sure does. its a conclusion ive drawn out for john: when i cite relevant scientific papers that refuted your claims, his response was that i am stupid. he cant have actually read the responses (or in the least understood them), as that was his reply containing no rebuttal or counter argument.

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  26. while were at it
    http://scienceblogs.com/erv/2010/01/endogenous_non-retroviruses.php

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  27. I responded back in May 2011. Here is my reply (2 emails combined for clarity here):

    Dear Livingstone,

    Thanks for the email and for alerting me to these references. I've finally checked them over and read the papers in detail. I do, however, disagree with your assessments of their import.

    The Bonner paper reports a family of retrovirus sequences in the chimp genome, but not in humans, which is consistent with infection in chimps but not in humans. That is not surprising (viruses are often species specific) nor is it inconsistent with the predictions I stated.

    The Lieber paper reports a similar occurrence in mice.

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  28. The Yohn paper is interesting and shows that PTERV1 viruses have inserted independently into similar locations in various apes. However, they did not do a detailed enough analysis to locate the exact locations at nucleotide resolution, so we don't know if the similar locations are exactly the same sites or if they are just close. For instance, they write: "Within the limits of this BAC-based end-sequencing mapping approach, 24 sites mapped to similar regions of the human reference genome (approximately 160 kb) and could not be definitively resolved as orthologous or non-orthologous." We know that viruses have sequence preferences for where they insert, and that there are insertion "hot-spots" in chromosomes where insertion is more likely, so it is not unexpected that viruses will preferentially insert in similar chromosomal locations independently in different closely related species (like African great apes).

    Yohn et al found 12 sites that could possibly be in the same exact chromosomal location. They tried to resolve three of them, and they were able to resolve two. Both were non-orthologous:

    [quote]
    For the three intervals putatively shared between macaque and chimpanzee, we attempted to refine the precise position of the insertions by taking advantage of the available whole-genome shotgun sequences for these two genomes. For each of the three loci, we mapped the precise insertion site in the chimpanzee and then examined the corresponding site in macaque (http://www.ncbi.nlm.nih.gov). In one case, we were unable to refine the map interval owing to the presence of repetitive rich sequences within the interval. In two cases, we were able to refine the map location to single basepair resolution (Figures S4 and S5). Based on this analysis, we determined that the sites were not orthologous between chimpanzee and macaque. It is interesting to note that this level of refined mapping in chimpanzee revealed 4- to 5-bp AT-rich target site duplications in both cases. These findings are consistent with an exogenous retrovirus source since proviral integrations typically target AT-rich DNA ranging from 4 to 6 bp in length [24]. Although the status of the remaining overlapping sites is unknown, these data resolve four additional sites as independent insertion events and suggest that the remainder may similarly be non-orthologous.
    [/quote]

    Unlike the others, the Barbulescu paper shows that humans lack a HERV-K insertion where other great apes have it, in exactly the same chromosomal location (at nucleotide resolution). So this is the closest we have to a "falsification" as I stated it. However, you will note that I was careful to word my claim in terms of organisms that are known to not be closely related, like dogs and humans. For closely related species, like humans, chimps, and gorillas, the story is different, precisely because we share a rather recent common ancestor with chimps and gorillas (they are the most closely related species to us). Discrepancies like that reported in the Barbulescu paper (among closely related species) are in fact expected due to simple population genetics, a phenomenon known as "incomplete lineage sorting". Here's a good explanation and image:

    http://www.flickr.com/photos/stevelewalready/2204204419/

    Lineage sorting, however, could not explain such a discrepancy between distantly related species like dogs and humans.

    Cheers,

    Douglas

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