Genomics Intelligent Design

Popcorn: How much of the genome is transcribed?

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All? Some? None?

Clark et al., The Reality of Pervasive Transcription:

Current estimates indicate that only about 1.2% of the mammalian genome codes for amino acids in proteins. However, mounting evidence over the past decade has suggested that the vast majority of the genome is transcribed, well beyond the boundaries of known genes, a phenomenon known as pervasive transcription [1]. Challenging this view, an article published in PLoS Biology by van Bakel et al. concluded that “the genome is not as pervasively transcribed as previously reported” [2] and that the majority of the detected low-level transcription is due to technical artefacts and/or background biological noise. These conclusions attracted considerable publicity [3]–[6]. Here, we present an evaluation of the analysis and conclusions of van Bakel et al. compared to those of others and show that (1) the existence of pervasive transcription is supported by multiple independent techniques; (2) re-analysis of the van Bakel et al. tiling arrays shows that their results are atypical compared to those of ENCODE and lack independent validation; and (3) the RNA sequencing dataset used by van Bakel et al. suffered from insufficient sequencing depth and poor transcript assembly, compromising their ability to detect the less abundant transcripts outside of protein-coding genes. We conclude that the totality of the evidence strongly supports pervasive transcription of mammalian genomes, although the biological significance of many novel coding and noncoding transcripts remains to be explored.

However, van Bakel et al. respond:

Clark et al. criticize several aspects of our study [1], and specifically challenge our assertion that the degree of pervasive transcription has previously been overstated. We disagree with much of their reasoning and their interpretation of our work. For example, many of our conclusions are based on overall sequence read distributions, while Clark et al. focus on transcript units and seqfrags (sets of overlapping reads). A key point is that one can derive a robust estimate of the relative amounts of different transcript types without having a complete reconstruction of every single transcript.

In this brief response, we first revisit what is meant by pervasive transcription, and its potential significance. We then discuss the major points raised by Clark et al. in the order presented in their critique. Finally, we demonstrate that conclusions very similar to those of our original study are reached with a dataset with far greater read depth, obtained by strand-specific sequencing of rRNA-depleted total RNA from a single cell type.

Thoughts?

8 Replies to “Popcorn: How much of the genome is transcribed?

  1. 1
    NickMatzke_UD says:

    More relevantly, from van Bakel et al:

    Clark et al. define pervasive transcription of a genome to mean “that the majority of its bases are associated with at least one primary transcript”, which is the same definition used in the ENCODE 1% paper [2]. We believe that this specific claim is not contested, nor is it particularly interesting. First, it has long been assumed that roughly half of the human genome comprises introns [3]. Second, the mechanisms that control the positions of initiation and termination of Pol II transcription, as well as RNA processing, are imperfect, such that low-level background transcripts from both physiologically relevant and non-canonical sites arise [4]–[6]. Blockage of surveillance mechanisms that normally degrade such “cryptic” transcripts greatly increases their abundance [7],[8].

    We acknowledge that the phrase quoted by Clark et al. in our Author Summary should have read “stably transcribed”, or some equivalent, rather than simply “transcribed”. But this does not change the fact that we strongly disagree with the fundamental argument put forward by Clark et al., which is that the genomic area corresponding to transcripts is more important than their relative abundance. This viewpoint makes little sense to us. Given the various sources of extraneous sequence reads, both biological and laboratory-derived (see below), it is expected that with sufficient sequencing depth the entire genome would eventually be encompassed by reads. Our statement that “the genome is not as not as pervasively transcribed as previously reported” stems from the fact that our observations relate to the relative quantity of material detected.

    Of course, some rare transcripts (and/or rare transcription) are functional, and low-level transcription may also provide a pool of material for evolutionary tinkering. But given that known mechanisms—in particular, imperfections in termination (see below)—can explain the presence of low-level random (and many non-random) transcripts, we believe the burden of proof is to show that such transcripts are indeed functional, rather than to disprove their putative functionality.

    This is pretty darn good evidence that a lot of that “pervasive transcription” is, well, junk RNA. (On a sequence-by-sequence basis. Their point is that the junk, even if transcribed a little bit by accident, isn’t transcribed much.)

    Larry Moran was saying all of this years ago…

  2. 2
    News says:

    Nick Matzke at 1 above 7/14/2011: “This is pretty darn good evidence that a lot of that “pervasive transcription” is, well, junk RNA.”

    Thank you.

  3. 3
    bornagain77 says:

    Just to note that the ‘trend’, for the last decade, in science has been steadily advancing the case that the genome is not nearly as ‘junky’ as neo-Darwinists had originally led us to believe, I feel Bakel et al, is making, primarily, a philosophically motivated response with very shaky empirical warrant for doing so;

    a few related notes:

    Francis Collins’s Junk DNA Arguments Pushed Into Increasingly Small Gaps in Scientific Knowledge – May 2011
    http://www.evolutionnews.org/2.....46251.html

    Jonathan Wells: On Francis Collins and Junk DNA – video
    http://www.youtube.com/watch?v=hksGZcqJ5h4

    Reference Notes For Jonathan Wells’ Book – The Myth Of Junk DNA – Hundreds of Studies Outlining Function for ‘Junk’ DNA
    http://docs.google.com/viewer?.....xHdM_e731g

    Evolutionary Biologist Richard Sternberg discusses modern genomics and junk DNA – June 2011 – audio podcast
    http://intelligentdesign.podom.....6_26-07_00

    Francis Collins, Darwin of the Gaps, and the Fallacy Of Junk DNA – video
    http://www.evolutionnews.org/2.....40361.html

    Excerpt: Collins’ assertions several years ago concerning “junk DNA” have already been shown to be erroneous: This “junk” regulates the timing of DNA replication, tags sites that need their genetic material rearranged, guides RNA splicing and editing, helps chromosomes fold properly, and regulates embryo development.
    http://www.worldmag.com/articles/18207

    Getting Over the Code Delusion – From Junk to Living Organism – November 2010

    Excerpt: So what’s going on? These puzzles turn out to be intimately related. As organisms rise on the evolutionary scale, they tend to have more “junk DNA.” Noncoding DNA accounts for some 10 percent of the genome in many one-celled organisms, 75 percent in roundworms, and 98 percent in humans. The ironic suspicion became too obvious to ignore: maybe it’s precisely our “junk” that differentiates us from water fleas. Maybe what counts most is not so much the genes themselves as the way they are regulated and expressed. Noncoding DNA could provide the complex regulatory functions that direct genes toward service of the organism’s needs, including its developmental needs.

    That suspicion has now become standard doctrine — though a still much-too-simplistic doctrine if one stops there. For noncoding as well as coding DNA sequences continue unchanged throughout the organism’s entire trajectory of differentiation, from single cell to maturity. Lillie’s point therefore remains: it is hardly possible for an unchanging complex to explain an ordered developmental stream. Constant things cannot by themselves explain dynamic processes.
    http://www.thenewatlantis.com/.....e-delusion

    etc.. etc..

  4. 4
    bornagain77 says:

    Seems like the whole fallacious, and theologically based, vestigial organ argument, that Darwinists use to use to support their theory, is being played out once again on the molecular level:

    The Myth of Junk DNA Grows With the Telling – July 2011
    Since the publication of Jonathan Wells’ The Myth of Junk DNA, many articles have come out documenting more functions for non-protein-coding DNA. It looks like Dr. Wells sampled the water just as the tide was starting to come in, and it’s still rising. Richard Dawkins, Larry Moran, and other proponents of junk DNA should move to higher ground.
    http://www.evolutionnews.org/2.....48311.html

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

  5. 5
    NickMatzke_UD says:

    bornagain77 — links do not equal arguments except when they don’t address the points under discussion. The above quote says that even small amounts of random DNA can be introduced to these experiments and gets detectably expressed as RNA at low levels. This is strong evidence that low-level transcription is mostly biological and experimental noise, not functional.

    Re: junk DNA — why do no ID proponents ever mention, let alone explain, the simple fact that some vertebrates have 10+ times more DNA than humans, and other vertebrates 10 times less? Why do some onions have 5 times more DNA than other onions? Why do some ferns have 70 times more DNA than humans?

    Why should anyone take seriously the idea that this all functional? Especially when most of the variation is due to variable, apparently parasitical sequences?

  6. 6
    NickMatzke_UD says:

    Correction:

    “links do not equal arguments except when they don’t address the points under discussion.”

    –>

    “links do not equal arguments when they don’t address the points under discussion. “

  7. 7
    bornagain77 says:

    Nick, you ask;

    ‘why do no ID proponents ever mention, let alone explain, the simple fact that some vertebrates have 10+ times more DNA than humans, and other vertebrates 10 times less? Why do some onions have 5 times more DNA than other onions? Why do some ferns have 70 times more DNA than humans?’

    Well despite your claim that C-values are ignored by IDists,,, genome sizes are known to vary widely between Kinds/Species despite their differences in complexity and this mystery is known as the c-value enigma:

    C-value enigma
    Excerpt: it was soon found that C-values (genome sizes) vary enormously among species and that this bears no relationship to the presumed number of genes (as reflected by the complexity of the organism). For example, the cells of some salamanders may contain 40 times more DNA than those of humans. Given that C-values were assumed to be constant because DNA is the stuff of genes, and yet bore no relationship to presumed gene number, this was understandably considered paradoxical;
    http://en.wikipedia.org/wiki/C-value_enigma

    And yet, even though this C-value enigma is paradoxical to the materialistic, neo-Darwinian, point of view, since there is no direct correlation to the ‘material’ bases of genome sizes and the ‘information’ that is erroneously presupposed to have emerged for that bases, from a design point of view we would expect genome sizes to vary with design constraints imposed in trying to achieve ‘optimal design’ for any particular life-form; For instance:

    “There is strong positive correlation, however, between the amount of DNA and the volume of a cell and its nucleus – which effects the rate of cell growth and division. Furthermore, in mammals there is a negative correlation between genome size and rate of metabolism. Bats have very high metabolic rates and relatively small genomes. In birds, there is a negative correlation between C-value and resting metabolic rate. In salamanders, there is also a negative correlation between genome size and the rate of limb regeneration.”
    Jonathan Wells – The Myth Of Junk DNA – page 85

    THE ALLOMETRIC RELATIONSHIP BETWEEN GENOME SIZE (C-VALUE) AND TOTAL METABOLIC ENERGY PER LIFESPAN, PER UNIT BODY MASS IN ANIMALS
    Excerpt: this show(s) that,,, the higher total life energy per unit body mass leads to smaller C-value.
    http://www.sustz.com/Proceedin.....ANASOV.pdf

    Thus Nick there is a ‘design constraint’ correlation that you have, in your haste to impose your atheistic dogma on the evidence, overlooked. But please note Nick, that behind your whole junk DNA presuppositions is the underlying ‘bad design’ Theological argument in which you have presupposed “God would not have done it that way”. This is the same basic type of ‘Theological’ argumentation that infused Darwin’s book Origin of Species; To put it mildly Nick, considering the level of complexity being dealt with and the utter poverty of material processes to account for the generation of any of that complexity, I should think you would be far more humble in your presupposition that you actually know more than God so as to advise Him on how He should or should not design something!

    notes:

    Here is a peer-reviewed paper which points out the fact Darwin based his arguments primarily on Theology, not science;:

    Charles Darwin, Theologian: Major New Article on Darwin’s Use of Theology in the Origin of Species – May 2011
    http://www.evolutionnews.org/2.....46391.html

    And the Theological arguments from neo-Darwinists continue to this day;

    From Philosopher to Science Writer: The Dissemination of Evolutionary Thought – May 2011
    Excerpt: The powerful theory of evolution hangs on this framework of thought that mandates naturalism. The science is weak but the metaphysics are strong. This is the key to understanding evolutionary thought. The weak arguments are scientific and the strong arguments, though filled with empirical observation and scientific jargon, are metaphysical. The stronger the argument, the more theological or philosophical.
    http://darwins-god.blogspot.co.....riter.html

    Evolution Is Religion–Not Science by Henry Morris, Ph.D.
    Excerpt: Evolution is promoted by its practitioners as more than mere science. Evolution is promulgated as an ideology, a secular religion—a full-fledged alternative to Christianity, with meaning and morality,,, Evolution is a religion. This was true of evolution in the beginning, and it is true of evolution still today.
    Darwinian atheist Michael Ruse – Prominent Philosopher

    And the theological ‘bad design’ argument, which Darwinists unwittingly continually use to try to make their case, is actually its own independent discipline of study within Theology itself called Theodicy:

    Is Your Bod Flawed by God? – Feb. 2010
    Excerpt: Theodicy (the discipline in Theism of reconciling natural evil with a good God) might be a problem for 19th-century deism and simplistic natural theology, but not for Biblical theology. It was not a problem for Jesus Christ, who was certainly not oblivious to the blind, the deaf, the lepers and the lame around him. It was not a problem for Paul, who spoke of the whole creation groaning and travailing in pain till the coming redemption of all things (Romans 8).
    http://www.creationsafaris.com.....#20100214a

    Here is an atheist professor who openly proselytizes his religion in his classroom:

    Dr. Will Provine on Religion and Creationism – video
    https://www.youtube.com/watch?v=nnMjaw8zUxQ

    Nick, do you actually think that it is OK for Provine to do this??? Myself, I think Perhaps neo-Darwinian evolution should be moved out of science class to Theology class??? Perhaps even astrology class;

    Is evolution pseudoscience?
    Excerpt:,,, Thus, of the ten characteristics of pseudoscience listed in the Skeptic’s Dictionary, evolution meets nine. Few other?pseudosciences — astrology, astral projection, alien abduction, crystal power, or whatever — would meet so many.
    http://creation.com/is-evolution-pseudoscience

    “Certainly, my own research with antibiotics during World War II received no guidance from insights provided by Darwinian evolution. Nor did Alexander Fleming’s discovery of bacterial inhibition by penicillin. I recently asked more than 70 eminent researchers if they would have done their work differently if they had thought Darwin’s theory was wrong. The responses were all the same: No.
    Philip S. Skell – Professor at Pennsylvania State University.

    Podcasts and Article of Dr. Skell
    http://www.evolutionnews.org/2.....40981.html

    Darwinian Medicine and Proximate and Evolutionary Explanations – Michael Egnor – neurosurgeon – June 2011
    http://www.evolutionnews.org/2.....47701.html

    Science Owes Nothing To Darwinian Evolution – Jonathan Wells – video
    http://www.metacafe.com/watch/4028096

  8. 8
    bornagain77 says:

    Nick, you ask;

    ‘why do no ID proponents ever mention, let alone explain, the simple fact that some vertebrates have 10+ times more DNA than humans, and other vertebrates 10 times less? Why do some onions have 5 times more DNA than other onions? Why do some ferns have 70 times more DNA than humans?’

    Well despite your claim that C-values are ignored by IDists,,, genome sizes are known to vary widely between Kinds/Species despite their differences in complexity and this mystery is known as the c-value enigma:

    C-value enigma
    Excerpt: it was soon found that C-values (genome sizes) vary enormously among species and that this bears no relationship to the presumed number of genes (as reflected by the complexity of the organism). For example, the cells of some salamanders may contain 40 times more DNA than those of humans. Given that C-values were assumed to be constant because DNA is the stuff of genes, and yet bore no relationship to presumed gene number, this was understandably considered paradoxical;

    And yet, even though this C-value enigma is paradoxical to the materialistic, neo-Darwinian, point of view, since there is no direct correlation to the ‘material’ bases of genome sizes and the ‘information’ that is erroneously presupposed to have emerged for that bases, from a design point of view we would expect genome sizes to vary with design constraints imposed in trying to achieve ‘optimal design’ for any particular life-form; For instance:

    “There is strong positive correlation, however, between the amount of DNA and the volume of a cell and its nucleus – which effects the rate of cell growth and division. Furthermore, in mammals there is a negative correlation between genome size and rate of metabolism. Bats have very high metabolic rates and relatively small genomes. In birds, there is a negative correlation between C-value and resting metabolic rate. In salamanders, there is also a negative correlation between genome size and the rate of limb regeneration.”
    Jonathan Wells – The Myth Of Junk DNA – page 85

    THE ALLOMETRIC RELATIONSHIP BETWEEN GENOME SIZE (C-VALUE) AND TOTAL METABOLIC ENERGY PER LIFESPAN, PER UNIT BODY MASS IN ANIMALS
    Excerpt: this show(s) that,,, the higher total life energy per unit body mass leads to smaller C-value.
    http://www.sustz.com/Proceedin.....ANASOV.pdf

    Thus Nick there is a ‘design constraint’ correlation that you have, in your haste to impose your atheistic dogma on the evidence, overlooked. But please note Nick, that behind your whole junk DNA presuppositions is the underlying ‘bad design’ Theological argument in which you have presupposed “God would not have done it that way”. This is the same basic type of ‘Theological’ argumentation that infused Darwin’s book Origin of Species; To put it mildly Nick, considering the level of complexity being dealt with and the utter poverty of material processes to account for the generation of any of that complexity, I should think you would be far more humble in your presupposition that you actually know more than God so as to advise Him on how He should or should not design something!

    notes:

    Here is a peer-reviewed paper which points out the fact Darwin based his arguments primarily on Theology, not science;:

    Charles Darwin, Theologian: Major New Article on Darwin’s Use of Theology in the Origin of Species – May 2011
    http://www.evolutionnews.org/2.....46391.html

    And the Theological arguments from neo-Darwinists continue to this day;

    From Philosopher to Science Writer: The Dissemination of Evolutionary Thought – May 2011
    Excerpt: The powerful theory of evolution hangs on this framework of thought that mandates naturalism. The science is weak but the metaphysics are strong. This is the key to understanding evolutionary thought. The weak arguments are scientific and the strong arguments, though filled with empirical observation and scientific jargon, are metaphysical. The stronger the argument, the more theological or philosophical.
    http://darwins-god.blogspot.co.....riter.html

    Evolution Is Religion–Not Science by Henry Morris, Ph.D.
    Excerpt: Evolution is promoted by its practitioners as more than mere science. Evolution is promulgated as an ideology, a secular religion—a full-fledged alternative to Christianity, with meaning and morality,,, Evolution is a religion. This was true of evolution in the beginning, and it is true of evolution still today.
    Darwinian atheist Michael Ruse – Prominent Philosopher

    And the theological ‘bad design’ argument, which Darwinists unwittingly continually use to try to make their case, is actually its own independent discipline of study within Theology itself called Theodicy:

    Is Your Bod Flawed by God? – Feb. 2010
    Excerpt: Theodicy (the discipline in Theism of reconciling natural evil with a good God) might be a problem for 19th-century deism and simplistic natural theology, but not for Biblical theology. It was not a problem for Jesus Christ, who was certainly not oblivious to the blind, the deaf, the lepers and the lame around him. It was not a problem for Paul, who spoke of the whole creation groaning and travailing in pain till the coming redemption of all things (Romans 8).
    http://www.creationsafaris.com.....#20100214a

    Here is an atheist professor who openly proselytizes his religion in his classroom:

    Dr. Will Provine on Religion and Creationism – video
    https://www.youtube.com/watch?v=nnMjaw8zUxQ

    Nick, do you actually think that it is OK for Provine to do this??? Myself, I think Perhaps neo-Darwinian evolution should be moved out of science class to Theology class??? Perhaps even astrology class;

    Is evolution pseudoscience?
    Excerpt:,,, Thus, of the ten characteristics of pseudoscience listed in the Skeptic’s Dictionary, evolution meets nine. Few other?pseudosciences — astrology, astral projection, alien abduction, crystal power, or whatever — would meet so many.
    http://creation.com/is-evolution-pseudoscience

    “Certainly, my own research with antibiotics during World War II received no guidance from insights provided by Darwinian evolution. Nor did Alexander Fleming’s discovery of bacterial inhibition by penicillin. I recently asked more than 70 eminent researchers if they would have done their work differently if they had thought Darwin’s theory was wrong. The responses were all the same: No.
    Philip S. Skell – Professor at Pennsylvania State University.

    Podcasts and Article of Dr. Skell
    http://www.evolutionnews.org/2.....40981.html

    Darwinian Medicine and Proximate and Evolutionary Explanations – Michael Egnor – neurosurgeon – June 2011
    http://www.evolutionnews.org/2.....47701.html

    Science Owes Nothing To Darwinian Evolution – Jonathan Wells – video
    http://www.metacafe.com/watch/4028096

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