Friday, November 12, 2010

Allele-Specific DNA Methylation and the World of Epigenetics

The ability of species to adapt to changing and challenging conditions is remarkable and due to a wide variety of molecular mechanisms. Many of these mechanisms fall into the broad category of epigenetics of which we are still learning the details.

One of the best known epigenetic mechanisms is DNA methylation in which a small molecule (a methyl group) is added to the DNA macromolecule at particular locations. Like a barcode or marker, the methyl group indicates, for instance, which genes in the DNA are to be turned on. This DNA methylation is accomplished via the action of a protein machine that adds the methyl group at precisely the right location in the DNA strand.

The methylation occurs at certain target sites along the DNA sequence where specific short DNA sequences appear. These sequences are found by protein machines as they move along the DNA. The protein machines search for these sequences and add a methyl group to the appropriate DNA base.

The protein machine binds to the DNA, twists the helix so the DNA base rotates into a precisely shaped pocket in the protein, and the protein then facilitates the transfer of the methyl group from a short donor molecule to the DNA base.

In bacterial studies it has been found that the short donor molecule does more, however, than just supply a methyl group. It also helps to control the protein. First, the short donor molecule binds to the pocket of the protein so the methyl group is ready for transfer. But the donor molecule also binds to another site on the protein. This binding serves to alter the structure of the protein, enhancing its function. So the protein is designed to do its job when it is charged with a donor molecule.

But not all of the DNA target sequences are methylated. This complex DNA methylation function doesn’t occur if the target sequence is protected by another protein that binds to the sequence. This protein binds to some of these DNA target sequences but not all. The result is a particular DNA methylation pattern which influences which genes are expressed.

Mark the marker

Furthermore, the methyl group marker can, itself, be modified. That is, the mark can be marked, thus adding another layer of information to the epigenetic mechanism. For instance, the methyl group can be hydroxylated. And of course a different molecular machine is required for the task, and the information of when and where to go to work is needed.

All of this makes for a complex DNA methylation pattern which is superimposed on the DNA macromolecule. In fact, this encoding of epigenetic information varies substantially across different regions of the DNA and it varies between the two alleles of a given gene and this allele-specific methylation can be tissue-specific.
DNA methylation is also transmitted across generations, but in the embryonic stages of development can be erased by yet another protein machine.

Histones

In addition to the DNA macromolecule, methyl groups are also used to tag the histone proteins about which the DNA is wrapped. The histones have a hub, around which the DNA wraps, and a tail that sticks out on which chemical markers are attached. As with DNA, these markers are signals for the protein machinery. And like DNA, these tags are removed as well. Such modifications and removal of these chemical tags means that these codes are dynamic, and there are protein inspectors that double-check these complex encodings.

These subtle codes are also context dependent. In one type of cell a histone modification may turn off a gene whereas in another type of cell the same histone modification may turn on the gene.

In addition to methylation, histones can also vary by tiny differences in their amino acid sequence. This histone sequence variation serves as yet another type of tag used for gene regulation.

Furthermore, histone variants are not merely static sign posts that influence gene expression. These variants are moved, by other proteins, between different locations in the genome, resulting in migration patterns that occur in the embryonic development phases.

Did epigenetics evolve?

Evolutionists do not think twice about the question of whether the epigenetic world evolved. Of course it did. Evolution is a fact, and so all of biology is its handiwork. This despite the “hint at an unimagined complexity of the genome” as one science writer admitted.

With evolution we must be believe that levels of complexity we could never have dreamed of, and which contradict evolution’s predictions, arose from random mutations (no, natural selection doesn’t change that fact, the mutations are still random). And as those complex machines and mechanisms arose, we must either believe there would be no use for them, or just luckily there would be some intermediate use for them that they happened to fulfill, while waiting for a later time for their epigenetic functions to be realized.

In fact, beyond sheer speculation, there is no explanation for how the epigenetic world evolved. The conviction that it did evolve is not a scientific conclusion—it comes from the belief that evolution is a fact.

Of course none of this means that the epigenetic world absolutely could not have evolved. But there certainly is no justification for taking up positions at the other end of the spectrum. There is no scientific justification for proclaiming that evolution, including the evolution of the epigenetic world, is an undeniable fact, as evolutionists insist.

It is unfortunate that we stake out such hard-edged, dogmatic positions that can be defended only by shouting down and blackballing dissent. In spite of the science, evolution must be true and all who disagree must be rejected.

Evolutionists are not the first, and undoubtedly won’t be the last, to engage in religious narrow-mindedness and parochial intolerance, in defiance of the facts. Religion drives science, and it matters.

45 comments:

  1. Cornelius Hunter:

    "In fact, beyond sheer speculation, there is no explanation for how the epigenetic world evolved. The conviction that it did evolve is not a scientific conclusion—it comes from the belief that evolution is a fact."
    =======

    It's certainly a thorn in any Evolutionist's side with regard behavioral issues. Bad behavioral choices by a Patriarch resulting in degenerative consequences even generations later ??? Hmmmmmmmmm!!!

    As Marcus Pembrey concluded on the Horizon documentary, if someone chooses to take a cavalier(I could care less) attitude about their personal life choice of boozing it up or smoking like a train (or for that matter any number of perverted behavioral life choices) and so what if I die before 60, he said you may want to think about your choice and attitude's effect on your descendants. Not really what the modern world wants to hear.

    When you hear the bottomfeeder proponants(that is in the information theory sense) dogmatically espousing "INFORMATION" is not a top down phenomena, Really ???

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  2. Eocene:

    "As Marcus Pembrey concluded on the Horizon documentary, if someone chooses to take a cavalier(I could care less) attitude about their personal life choice of boozing it up or smoking like a train (or for that matter any number of perverted behavioral life choices) and so what if I die before 60, he said you may want to think about your choice and attitude's effect on your descendants."

    That's right! Epigenetic inheritance will teach those gay alcoholic bacteria to lead better lives.

    Hey E. coli - don't want to give up smoking? Here are some extra methyl-groups on your DNA! Let that be a lesson for you!

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  3. Well to conclude on a scriptural note:

    Romans 8:22 (Amplified Bible)

    22 "We know that the whole creation [of irrational creatures] has been moaning together in the pains of labor until now."

    So all creation is subject and in pain because of the imerfections of the human genome. Hmmmm!!! Now notice the cross referenced scriptures from a more modern day translation:

    Jeremiah 12:4 (GOD’S WORD Translation)


    4 "How long will the land mourn?
    How long will the plants in every field remain dried up?
    The animals and the birds are dying, because people are wicked.
    They think that God[a] doesn’t know what they are doing."

    AND

    Jeremiah 12:11 (New Living Translation)

    11 "They have made it an empty wasteland;
    I hear its mournful cry.
    The whole land is desolate, and no one even cares."

    Now what self-respecting Environmentalist could ever disagree with that ???

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  4. Troy:

    "That's right! Epigenetic inheritance will teach those gay alcoholic bacteria to lead better lives.

    Hey E. coli - don't want to give up smoking? Here are some extra methyl-groups on your DNA! Let that be a lesson for you!"
    ======

    What's wrong, what happened ???

    Did Marcus Pembrey come along and step all over your precious Worldview ???

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  5. continued from above . .

    None of these massive large scale degenerative phenomenas were ever orignally a part of the natural world until Scientists created money making products for the Big-Business pimps who employ them. Faced with the evidence of the cause and effect epigenetics consequences of their actions, Big-Biz has pumped alot of money into fighting the research as opposed to helping make a change for the better.

    This puts the average evolutionist on the fence. While they are usually known for championing environmental causes (tho not so much as one to be found here), there is also that nagging social implication of an increase in homosexuality as the result of environmental ruin. To an evolutionist, you cannot separate the idealogy/politics/philosophy from the science. Look at most of their blogs. It's not about science.

    http://www.ourstolenfuture.org

    Well there it is. The website has nothing to do with anything Creationisty. Any self respecting radical eco-terrorist would even approve.

    Unfortunately for many it will take to much reading to even care. Some will find it boring while others too political. But it doesn't bode well for evo-world, since they'd have to make excuses for their holymen (scientists) for bringing this on.

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  6. This should have been above my last post, but oh well . .

    Interestingly, animals, fish, plants, birds etc are not effected by this the same way humans are. Obviously they do not make the same stupid choice reasonings humans make. However, they are subject to the degenerative epigenetic actions of human choices. One of the listed of categories in any epigenetics FAQs out there are about the genomic imprinting effects of Bisphenol-A (BPA) found in the plastics of our enlightened modern day world of supposed "brought to you by science" modern convenience. It's effects on nature (especially aquatic world) is disruption of the Endocrine system which fouls up the information regarding breeding, sexual function and perhaps sterility early on at the initial fetal development. It's causing some wild species to actually go extinct, but no one wants to hear about that. Why ??? Because no one likes the idea of making personal behavioral choice changes that would actually be the responsible thing to do. Hey, it's all about unrestrictive freedom, right ???

    In 2009 last year, there were a number of scientific articles championing "Homosexuality" as a normal trait to be found everywhere in nature. So Homosexual behavior was tauted as something normal, not degenerate. Yet back in the 1980s, researchers were actually warning the scientific world about the dangers of BPA in the environment because of the prevalence in some areas where it was found that gay pairs of both birds and fish were trying to mate and nest and reproduction was halted as a result of degerative effects of environmental polution involving BPAs. Many of the same effects are also having the same detrimental effects on humans, but the subject is so politically and philosophically charged and contaminated, no one wants to consider it as a possible cause of homosexual behavior.

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  7. Eocene, this is 2010. It's OK it you wish to come out of the closet. There's no reason to hide the truth by projecting anti-gay bigotry and anger. We won't reject you because of your innate orientation.

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  8. Thorton said...

    Eocene, this is 2010. It's OK it you wish to come out of the closet. There's no reason to hide the truth by projecting anti-gay bigotry and anger. We won't reject you because of your innate orientation.

    ========================

    You would think that Christians stop the anti gay nonsense now. However gays are not the only ones they seem to blame all the ills of the world on.

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  9. Ambiorix:

    "You would think that Christians stop the anti gay nonsense now. However gays are not the only ones they seem to blame all the ills of the world on."
    =======

    There's nothing anti-gay or homophobic about the research information found on http://www.ourstolenfuture.com and the negative response and excuse making prove that this is more of a political games issue as opposed to anyone actually taking serious what major parts of Science have done to our Earth's environment.

    Religion and Money drive science and it shows.

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  10. Hunter in his original post (which deserves a bit of attention):

    There is no scientific justification for proclaiming that evolution, including the evolution of the epigenetic world, is an undeniable fact, as evolutionists insist.

    That there has been a hereditary lineage of living forms throughout geological history is well enough supported by evidence to be scored a fact by science. That any particular molecular mechanism in biology evolved along with those living forms is a logical corollary. That we don't yet know - or may never know - the historical details is not a refutation of that corollary: it's just a measure of the limits of current knowledge.

    All of science (and all of human perception) is hypothesis-laden and provisional.

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  11. From Richard Dawkins bible:

    Romulans 1:1 "Label thy opponent ASAP"

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  12. Cornelius:
    There is no scientific justification for proclaiming that evolution, including the evolution of the epigenetic world, is an undeniable fact, as evolutionists insist.

    There's not much justification to deny the fact that life evolved over time, and I think that's what evolutionists refer to when speaking of the "fact" of evolution. However, the mechanisms by which this occurred, including the mechanisms that produced the "epigenetic world" should of course be open to alternative explanatory hypotheses, provided such hypotheses involve mechanisms that can be in some way tested and observed in nature.

    For example, the central concept behind modern evolutionary theory is that random mutations create variability in populations and that natural selection filters out these variations, such that individuals that are in some way better suited to their environment survive differentially. The particulars of what constitutes “better suited” is of course dependent on the population and environment in question.

    Both random mutation and natural selection can be tested and observed in nature so we know demonstrably that a) mutations can and do occur and b) natural selection can and does act on variations within a population with measurable results (the Grant's study of Galapagos finches is a good example of this). Whether or not RM + NS is enough to drive speciation is another question. Nevertheless, the fact that we have a demonstrated mechanism that potentially explains the variety of life we see around us is one of the strengths of modern evolutionary theory.

    The problem with alternative theories to date is that they have not offered any form of a testable or demonstrable mechanism. Intelligent design theory in particular offers nothing in the way of a mechanism that would drive speciation. It is at its core merely a critique of the RM + NS paradigm. Until such time as an alternative, testable mechanism is proposed, scientists will be hesitant to abandon an existing theory that has so far had great explanatory power. That doesn't of course imply that it explains everything and that there are no mysteries yet to solve, but there is no reason to abandon evolutionary theory based solely on some gap in our current understanding.

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  13. I really read the post thoroughly, but I don't get it. What exactly is the problem for evolution?

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  14. Norm Olsen you state:

    'but there is no reason to abandon evolutionary theory based solely on some gap in our current understanding.'

    ,,,Are you appealing to a Darwin of the gaps?

    Francis Collins, Junk DNA, Evolution and "Darwin of the Gaps"
    http://www.evolutionnews.org/2010/11/francis_collins_is_one_of040361.html

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  15. second opinion said...

    I really read the post thoroughly, but I don't get it. What exactly is the problem for evolution?


    There's no problem at all for evolution. The problem is with the scientifically ignorant mouth-breathers who feel threatened by scientific reality because it conflicts with their narrow religious beliefs. Their solution of course is to rant and scream and deny reality instead of critically reevaluating their views in light of the evidence.

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  16. Okay, maybe as a follow up question. Is it only because of the complexity that this DNA methylation can't have evolved? If so is this system more or less complex than the human eye?

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  17. Epigenetic effects rarely persist more than a few generations, and thus play an extremely minor role in genetic change in populations over time.

    Dave Wisker

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  18. Dave Wisker:

    "Epigenetic effects rarely persist more than a few generations, and thus play an extremely minor role in genetic change in populations over time."

    Is the jury out on that? In their 2009 Quarterly Review of Biology paper Jablonka & Raz list quite a few examples of long-term stability. Especially in uni-cellular organisms. Could be a different story for multi-cellulars that use epigenetic marks during development and cell differentiation.

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  19. Dave Wisker:

    "Epigenetic effects rarely persist more than a few generations, and thus play an extremely minor role in genetic change in populations over time."
    =======

    Not true, they can actually be compounded by other negative additions by the later generations. In most all cases the effects are always negative.

    It's like starting out with a perfect cake mould. Take a hammer and put a small ding in it and then proceed to make a cake. It's not exactly a perfect copy of the original, but it's close. Now make a mould of that cake, but before you make a replication of that first generation cake, take that hammer and put another ding in it's side, then make a cake. The 3rd cake now has not only the first flaw, but also the second flaw and is further away from looking like that original perfect cake mould we started out with. Now times this times 10s of thousands of generations and what does that cake look like ??? Hardly anything like the original.

    This is what has happened to the human family. The constant degeneration of human society and our planet's environment truthfully does bare this out. The Horizon documentary with researcher Marcus Pembrey admitted that traditionally science has always looked at DNA in terms of materialist mechanics, but modern day discoveries are finding out that there is more to it than that. Behavior drives genetics and it matters.

    This is why Marcus Pembrey and his fellow colleagues have been branded a Heretic and damned to materialist Hell for thinking and relating the reality of what is actually happening outside the Scientifism's Idealogical Box. Surprise Surprise!!!

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  20. second_opinion:

    "Okay, maybe as a follow up question. Is it only because of the complexity that this DNA methylation can't have evolved? If so is this system more or less complex than the human eye?"
    =======

    "The Ghost In Your Genes"
    http://video.google.com/videoplay?docid=1128045835761675934#

    Sorry, but i don't have the ability or tools here to provide an actual link. Others have that ability, but maybe they purchased blog tools for this, I'm not sure.

    Anyway, on your question here:
    "Is it only because of the complexity that this DNA methylation can't have evolved?"

    and the last subtitle at the bottom of Cornelius' O.P. and his following paragraphs under the concluding title:
    "DID EPIGENETICS EVOLVE?"

    If you watch that entire documentary, it's the woman narrator who expresses it this way.
    " so just what was evolution's purpose was in creating epigenetics?" Really, "evolution's purpose" ??? That's basically it.

    Seriously that is the extent of the documentaries mention of evolutionary philosophy injection being introduced. It is assumed as usual to be a fact. There's no proof other than the priori of it's philosophical mandated factual existance. But surely never the less evolution must have done it. It's almost as if Emperor worship was required by the Panel of Peers in order for the program to pass the grade. Simply offer a pinch of incense (which means merely just referencing the word "evolution" in the documentary) before an burning alter in front of Charles Darwin's image.

    At the very least the documentary is interesting without mention of anyone's religio/politico beliefs, that is either evo-creo or id.

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  21. Eocene,
    You can use html tags for formatting and for embedding links. The syntax for links is:

    <a href="URL">TITLE</a>

    Replace URL with your link address, and replace TITLE with the text you want to appear as the link.

    For example here, is the formatting for the link you provided:

    <a href="http://video.google.com/videoplay?docid=1128045835761675934#">The Ghost In Your Genes</a>

    and as an embedded link:

    The Ghost In Your Genes

    ReplyDelete
  22. --------"Is the jury out on that? In their 2009 Quarterly Review of Biology paper Jablonka & Raz list quite a few examples of long-term stability. Especially in uni-cellular organisms. Could be a different story for multi-cellulars that use epigenetic marks during development and cell differentiation."-----------

    That would be expected in unicellular organisms, and in eukaryotic taxa where (as Jablonka & Raz note) there is a "lack of segregation between soma and germline", such as plants and fungi.

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  23. If every organism has epigenetic mechanisms, then that would seem to indicate that these mechanisms are necessary for all life. So how did life survive before epigenetic mechanisms evolved?

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  24. Norm Olsen:

    "Eocene,
    You can use html tags for formatting and for embedding links. The syntax for links is:"
    =======

    Well thanks Norm, I appreciate that. No matter how one may view the subject matter, that documentary and the subject epigenetics and genomic imprinting itself is fascinating.

    Thanks again.

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  25. How did you discern DNA methylation is designed?

    By what mechanism was it designed?

    How did you rule out it could not have evolved from simpler systems (e.g. the restriction modification system)?
    http://en.wikipedia.org/wiki/Restriction_enzyme

    Why does this design fail so often, for example, in accounting for the majority of cancers?
    http://www.epigeneticstation.com/dna-methylation-cancer/

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  26. RobertC:

    Lots of thnigs designed by humans fail. Cars break down, bridges collapse, computers crash.

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  27. natschuster-

    The evolutionary hypothesis would be that cancer has not been selected against because it is generally post reproductive, and largely a recent event of industrialized living.

    I was looking for a more specific explanatory design hypothesis than "stuff breaks."

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  28. The evolutionary hypothesis works for design as well. It was intended that it work long enough to allow the organism to reproduce.

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  29. natschuster said...

    The evolutionary hypothesis works for design as well. It was intended that it work long enough to allow the organism to reproduce.


    "It could have been designed that way" explains absolutely nothing. You might as well say "ZOMG it cudda been MAJIK!"

    Tell me nat - what evidence could we find that wouldn't be covered by the nebulous "It must have been designed that way"?

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  30. "It was intended that it work long enough to allow the organism to reproduce."

    Is, then, reproduction the only goal of design?

    Why do other design features (e.g. menopause and post-menopausal life span) seem to contradict the design feature you have discovered in the DNA methylation system?

    Also, no answer to the first three questions. Tsk.

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  31. natschuster: If every organism has epigenetic mechanisms, then that would seem to indicate that these mechanisms are necessary for all life. So how did life survive before epigenetic mechanisms evolved?

    Nat, if every computer now in service has microchips, then that would seem to indicate that microchips are necessary for all computers. So how did computers operate before the invention of the microchip?

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  32. Dereck:

    We know of computers that don't have microchips. And we understnadf how computers could have functioned with things like vacuum tubes. I don't think that the same thing could be said for organisms.

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  33. RobertC:

    I really don't know what the goal of the designer is. But maybe as long as an organism lives long enough to reproduce, it has fullfilled the designers purpose.

    And I'm not sure what the significance of cancer is, anyway. Most people don't die from cancer. And some people die from cancer before they have passed out if the reproductive years. Do cnacer rates suddenly go up after menopause? And men can remain fertile into old age. But they get cancer.

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  34. Thorton:

    People say that bad design can't be explained by a designer.

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  35. natschuster said...

    Thorton:

    People say that bad design can't be explained by a designer.


    Reference please. No one I've ever heard of says that.

    People say bad design can't be explained by an all powerful, all knowing, competent Designer, but that is something completely different.

    Is your Designer an incompetent boob?

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  36. Well, as long aa most of the time, the stuff He designed functions as intended, then He is at least a good enough Designer.

    And if engineers are studying organism to gety ideas, because so many organisms show superb, even optimal design, then the designer is pretty good.

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  37. natschuste: rAnd if engineers are studying organism to gety ideas, because so many organisms show superb, even optimal design, then the designer is pretty good.

    I study clouds to get ideas. Does that mean clouds are designed? I study canyons to get ideas. Does that mean canyons are designed?

    natschuster: Well, as long aa most of the time, the stuff He designed functions as intended, then He is at least a good enough Designer.

    That reminds me of the song they sing at church: "How Good Enough is our God," or that one by Rich Mullins: "Our God is a Good Enough God."

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  38. Do you study canyons to get ideas for designing structures like desalinization plants or efficinet airfoil designs?

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  39. An expert designer can choose to design less than perfect things. Often, this is the case when humans make things. There are usually trade offs caused by engineering, manufacturing, and economic constraints.

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  40. natschuster: An expert designer can choose to design less than perfect things. Often, this is the case when humans make things. There are usually trade offs caused by engineering, manufacturing, and economic constraints.

    Ah, that explains it then. God had 'engineering constraints' when making viruses. Or His shop didn't have the right manufacturing capability for the anti-birth-defect mechanism. Perhaps God ran out of money for the project before he could implement the anti-leukemia mechanisms.

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  41. Where did I ever say that the Designer was God? That's a theological issue. And its been discussed by theologians for centuries.

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  42. natschuster: Where did I ever say that the Designer was God?

    Puh-lease, nat. Don't insult people's intelligence like that.

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  43. Derick:

    I never said that we can infer from studying organisms that the designer was the God of the Bible. I don't think it can be infered from studying organism alone.

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  44. Natschuster wrote:

    Well, as long aa most of the time, the stuff He designed functions as intended, then He is at least a good enough Designer.

    What makes you think anything actually functions as the designer actually intended? Given an abstract designer, it would seem you couldn't actually know this without making additional assumptions.

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  45. DNA means deoxy ribose nucleic acid. DNA methylation is accomplished via the action of a protein machine that adds the methyl group at precisely the right location in the DNA strand. Thanks...

    DNA Methylation

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