Epigenetic information for gene expression (Was: Question)

Discussion in 'Health and medical' started by Cncabej, Feb 18, 2004.

  1. Cncabej

    Cncabej Guest

    On 17 Feb 2004 r norman wrote:

    >NC

    >You write: "I have a great deal of difficulty with statements like "the effect of the stimulus is
    >determined by stereochemical and thermodynamical properties of the stimulus." Let me try to make it
    >simpler . The spatial configuration of a hormone, and an antibody molecule, must be complementary
    >to that of a cell membrane receptor,and an antigen (this is a stereochemical property). But often
    >this may be not sufficient for two molecules to react, if they or their environment do not possess
    >enough energy that is necessary for that reaction to take place
    >(e.g., sequential phosphorylation of proteins in signal transduction pathways is necessary for
    > activation of those pathways).
    >
    >You also write: "Pineal gland cells are highly differentiated by whatever developmental processes
    >produce those cells. As a result, they express the genes involved in melatonin synthesis and are
    >capable of secreting melatonin. That is what I referred to as "their thing"." But, neither the type
    >of the cell nor "the thing" tells us anything about the cause of the expression of genes for
    >melatonin genes in pineal cells (otherwise I would expect you to elaborate on "why" the pineal
    >cells do what other cells can't). You can't explain an unknown with another. If we could
    >automatically figure out causes and mechanisms of gene expression by the type of cell this would
    >make unnecessary or obsolete one of the most important fields of modern biological research.
    >
    >Further you write: "In fact, the stimulation of the pineal is through the sympathetic nervous
    >system. That is, if you drop norepinephrine onto the pineal gland or artificially stimulate the
    >superior cervical
    ganglion,
    >the gland will release melatonin just as effectively as if you stopped shining light into the eye."
    >I am afraid that this contradicts your previous statements (that no information is needed for
    >expression of melatonin genes), but I am glad to find something we agree on. If you drop
    >epinephrine or if you artificially stimulate the pineal cells to synthesize melatonin, you are able
    >to do this because you know, you have information (in your expression you have "calculated") that
    >this will activate melatonin genes. A person that has no information could not do it. Similarly,
    >specific information is needed for specific activation of melatonin genes out of 30,000 genes in
    >billions/trillions of more than 2 hundred types of cells of our body.
    >
    >Now let me comment on your next and more encouraging statement. You write "The nervous system
    >"calculates" only that during daylight it should refrain from sending action potentials to the
    >superior cervical ganglion destined for the pineal and to resume those action potentials." In
    >principle, I agree completely with your ideas that
    >1. the nervous system controls both the activation and inactivation of melatonin genes,
    >2. that this CNS control is "calculated", in the meaning that the CNS knows when to send and when
    > to "refrain" from sending its signals for expression of genes for melatonin synthesis Granted
    > that a "calculated" response implies "information", from the above premises anyone might draw
    > the logical conclusion that the CNS is the source of the epigenetic information for melatonin
    > synthesis.
    >
    >But the last phrase shows that you still feel not comfortable with your above statement. You
    >write:"Nowhere does the nervous system calculate just how to activate any specific genes or how to
    >secrete any specific chemical." I could bring numerous examples proving the contrary. For now let
    >me just very briefly state that the CNS can express genes that no extracerebral cells can. It does
    >this by processing information on internal signals (hormones, growth factors) which HAVE NO ACCESS
    >to the CNS. For example, a stimulus on a drop in the level of estrogen in the blood is perceived
    >and processed in a specific neural

    >circuit. The chemical output of the processing (not the estrogen) of that stimulus via projections
    >of the neurons of that circuit on specific hypothalamic cells triggers the expression of the GnRH
    >(gonadotropin releasing hormone). This response is not determined by the stereochemical and
    >thermodynamical properties but from the processing (computational process) of the stimulus in the
    >respective
    neural
    >circuit. This is the reason why in nonneural cells the estrogen activates compeltely
    >different genes.
    >
    >P.S. as for your statement that "computational properties of neurons have nothing whatsoever to do
    > with" the secretion of melatonin, this is hardly compatible with the predominant opinion of
    > researchers that CNS responses are determined by computational properties of respective neural
    > circuits, and those properties change in response to various internal and external stimuli.
    >
    R. N. We are still far apart but maybe converging.

    Of course there is a sense of "information transfer" in all cell signaling, including the binding of
    a hormone or neurotranmitter to its receptor and the subsequent downstream pathway. Of course there
    is a sense of "information transfer" in the developmental process.

    It was my impression that you were trying to say that somehow neural circuits code "code
    information" for "turn on melatonin synthesis". I am simply saying that the pattern of neural
    connectivity automatically connects certain photosensitive cells to the sympathetic system. The
    nervous system computes something like "tell the pineal to go" or "don't tell the pineal to go".
    What the pineal does with that signal (sympathetic activation) is something "coded" into the pineal
    gland, not into neural computation.

    Yes, CNS cells can express specific genes and they can be induced to do so by stimuli or by hormones
    that never enter the CNS. Clearly what happens is that such stimuli are acting on sense organs that
    send action potentials into the CNS. The post-synaptic signaling pathway in specific CNS cells may
    well have the ability to activate genes -- the CREB system is a good example. My impression was that
    you were saying something like action potentials "code information" to "activate this specific
    gene." What I am saying is the the neural information coded is simply "I got this stimulus". What
    the target cell does with that information is totally irrelevant to the sensory system that detected
    the stimulus.

    R.A.

    First, I am glad we agree that a transfer of information generated in a specific circuit of the CNS
    is transmitted to the pineals cells. As for the nature of this information, it is essential to
    point out that

    -this is different from the genetic information contained in genes in the form of nucleotide
    sequences determining the sequence of amino acids in RNA and polypeptides.

    -the information that is sent to pineal cells does not preexist in the brain structure, but it is
    generated in the specific neural circuit, by processing the external stimulus. Being a result of a
    computational process (and having nothing to do with the sequence of nucleotides in DNA), this is
    information is EPIGENETIC.

    -this epigenetic information is necessary for expression of melatonin genes in the pineal cells,
    i.e. controls their expression (in your expression, the nervous system computes something like "tell
    the pineal to go" or "don't tell the pineal to go")

    I have difficulty in agreeing with you that "the neural information coded simply "I got this
    stimulus". What does the target cell do with that information is totally irrelevant to the sensory
    system that detected the stimulus."

    This is indefensible in view of the facts that
    1) the neural circuit sends a "computed" signal that specifically (not randomly) activates a
    specific signal transduction pathway, which makes possible expression of melatonin genes. At this
    point there is no choice for pineal cells; the expression of melatonin genes is unavoidable,
    predetermined by the epigenetic information those cells receive.

    2) The neural circuit not only generates the information for activation of melatonin genes, but it
    "knows" to exactly address that information to a certain type of cell (out of more than 2 hundred
    cell types) of a mammal), the only cells capable of producing melatonin, .

    Finally, I am interested to know more about your idea that such information transfer takes place in
    the developmental process.
     
    Tags:


  2. R Norman

    R Norman Guest

    On Wed, 18 Feb 2004 22:57:56 +0000 (UTC), [email protected] (CNCabej)
    wrote:

    >On 17 Feb 2004 r norman wrote:
    >
    >>NC
    >
    >>You write: "I have a great deal of difficulty with statements like "the effect of the stimulus is
    >>determined by stereochemical and thermodynamical properties of the stimulus." Let me try to make
    >>it simpler . The spatial configuration of a hormone, and an antibody molecule, must be
    >>complementary to that of a cell membrane receptor,and an antigen (this is a stereochemical
    >>property). But often this may be not sufficient for two molecules to react, if they or their
    >>environment do not possess enough energy that is necessary for that reaction to take place
    >>(e.g., sequential phosphorylation of proteins in signal transduction pathways is necessary for
    >> activation of those pathways).
    >>
    >>You also write: "Pineal gland cells are highly differentiated by whatever developmental processes
    >>produce those cells. As a result, they express the genes involved in melatonin synthesis and are
    >>capable of secreting melatonin. That is what I referred to as "their thing"." But, neither the
    >>type of the cell nor "the thing" tells us anything about the cause of the expression of genes for
    >>melatonin genes in pineal cells (otherwise I would expect you to elaborate on "why" the pineal
    >>cells do what other cells can't). You can't explain an unknown with another. If we could
    >>automatically figure out causes and mechanisms of gene expression by the type of cell this would
    >>make unnecessary or obsolete one of the most important fields of modern biological research.
    >>
    >>Further you write: "In fact, the stimulation of the pineal is through the sympathetic nervous
    >>system. That is, if you drop norepinephrine onto the pineal gland or artificially stimulate the
    >>superior cervical
    >ganglion,
    >>the gland will release melatonin just as effectively as if you stopped shining light into the
    >>eye." I am afraid that this contradicts your previous statements (that no information is needed
    >>for expression of melatonin genes), but I am glad to find something we agree on. If you drop
    >>epinephrine or if you artificially stimulate the pineal cells to synthesize melatonin, you are
    >>able to do this because you know, you have information (in your expression you have "calculated")
    >>that this will activate melatonin genes. A person that has no information could not do it.
    >>Similarly, specific information is needed for specific activation of melatonin genes out of 30,000
    >>genes in billions/trillions of more than 2 hundred types of cells of our body.
    >>
    >>Now let me comment on your next and more encouraging statement. You write "The nervous system
    >>"calculates" only that during daylight it should refrain from sending action potentials to the
    >>superior cervical ganglion destined for the pineal and to resume those action potentials." In
    >>principle, I agree completely with your ideas that
    >>1. the nervous system controls both the activation and inactivation of melatonin genes,
    >>2. that this CNS control is "calculated", in the meaning that the CNS knows when to send and when
    >> to "refrain" from sending its signals for expression of genes for melatonin synthesis Granted
    >> that a "calculated" response implies "information", from the above premises anyone might draw
    >> the logical conclusion that the CNS is the source of the epigenetic information for melatonin
    >> synthesis.
    >>
    >>But the last phrase shows that you still feel not comfortable with your above statement. You
    >>write:"Nowhere does the nervous system calculate just how to activate any specific genes or how to
    >>secrete any specific chemical." I could bring numerous examples proving the contrary. For now let
    >>me just very briefly state that the CNS can express genes that no extracerebral cells can. It does
    >>this by processing information on internal signals (hormones, growth factors) which HAVE NO ACCESS
    >>to the CNS. For example, a stimulus on a drop in the level of estrogen in the blood is perceived
    >>and processed in a specific neural
    >
    >>circuit. The chemical output of the processing (not the estrogen) of that stimulus via projections
    >>of the neurons of that circuit on specific hypothalamic cells triggers the expression of the GnRH
    >>(gonadotropin releasing hormone). This response is not determined by the stereochemical and
    >>thermodynamical properties but from the processing (computational process) of the stimulus in the
    >>respective
    >neural
    >>circuit. This is the reason why in nonneural cells the estrogen activates compeltely
    >>different genes.
    >>
    >>P.S. as for your statement that "computational properties of neurons have nothing whatsoever to do
    >> with" the secretion of melatonin, this is hardly compatible with the predominant opinion of
    >> researchers that CNS responses are determined by computational properties of respective
    >> neural circuits, and those properties change in response to various internal and external
    >> stimuli.
    >>
    >R. N. We are still far apart but maybe converging.
    >
    >Of course there is a sense of "information transfer" in all cell signaling, including the binding
    >of a hormone or neurotranmitter to its receptor and the subsequent downstream pathway. Of course
    >there is a sense of "information transfer" in the developmental process.
    >
    >It was my impression that you were trying to say that somehow neural circuits code "code
    >information" for "turn on melatonin synthesis". I am simply saying that the pattern of neural
    >connectivity automatically connects certain photosensitive cells to the sympathetic system. The
    >nervous system computes something like "tell the pineal to go" or "don't tell the pineal to go".
    >What the pineal does with that signal (sympathetic activation) is something "coded" into the pineal
    >gland, not into neural computation.
    >
    >Yes, CNS cells can express specific genes and they can be induced to do so by stimuli or by
    >hormones that never enter the CNS. Clearly what happens is that such stimuli are acting on sense
    >organs that send action potentials into the CNS. The post-synaptic signaling pathway in specific
    >CNS cells may well have the ability to activate genes -- the CREB system is a good example. My
    >impression was that you were saying something like action potentials "code information" to
    >"activate this specific gene." What I am saying is the the neural information coded is simply "I
    >got this stimulus". What the target cell does with that information is totally irrelevant to the
    >sensory system that detected the stimulus.
    >
    >N.C.
    >
    >First, I am glad we agree that a transfer of information generated in a specific circuit of the CNS
    >is transmitted to the pineals cells. As for the nature of this information, it is essential to
    >point out that
    >
    >-this is different from the genetic information contained in genes in the form of nucleotide
    >sequences determining the sequence of amino acids in RNA and polypeptides.
    >
    >-the information that is sent to pineal cells does not preexist in the brain structure, but it is
    >generated in the specific neural circuit, by processing the external stimulus. Being a result of a
    >computational process (and having nothing to do with the sequence of nucleotides in DNA), this is
    >information is EPIGENETIC.
    >
    >-this epigenetic information is necessary for expression of melatonin genes in the pineal cells,
    >i.e. controls their expression (in your expression, the nervous system computes something like
    >"tell the pineal to go" or "don't tell the pineal to go")
    >
    >I have difficulty in agreeing with you that "the neural information coded simply "I got this
    >stimulus". What does the target cell do with that information is totally irrelevant to the sensory
    >system that detected the stimulus."
    >
    >This is indefensible in view of the facts that
    >1) the neural circuit sends a "computed" signal that specifically (not randomly) activates a
    > specific signal transduction pathway, which makes possible expression of melatonin genes. At
    > this point there is no choice for pineal cells; the expression of melatonin genes is
    > unavoidable, predetermined by the epigenetic information those cells receive.
    >
    >2) The neural circuit not only generates the information for activation of melatonin genes, but it
    > "knows" to exactly address that information to a certain type of cell (out of more than 2
    > hundred cell types) of a mammal), the only cells capable of producing melatonin, .
    >
    >Finally, I am interested to know more about your idea that such information transfer takes place in
    >the developmental process.
    >
    >
    We are really just talking at cross purposes about the words used to describe how the nervous system
    works and how it interacts with effects to actually produce action.

    My comment about development merely reflects the fact that that is how the 200+ cell types come
    about in the first place. That is the reason that pineal cells express the genes to produce the
    enzymes necessary in synthesizing melatonin. A different type of cell expresses different genes and
    therefore, when stimulated by the sympathetic nervous system, does something quite different.

    The nervous system does "compute" the fact that "this message goes to the pineal, that message goes
    to the heart". The nervous system does "compute" just under what circumstances it should send those
    messages to those organs and when it should refrain from sending messages. I still claim that
    nothing about the neural computation relates to telling the specific target just what to do when it
    gets the message. It is the pineal cell or the heart cell that figures out just what to do when the
    sympathetic system tells it to "go".
     
  3. Peter F.

    Peter F. Guest

    "CNCabej" <[email protected]> wrote in message
    news:[email protected]...
    > On 17 Feb 2004 r norman wrote: What I am saying is the the neural information coded is simply "I
    > got this stimulus". What the target cell does with that information is totally irrelevant to the
    > sensory system that detected the stimulus.

    Most likely, this what-you-wrote is just another case of excusable 'eitheroring' or pidgeon-holing
    -- or 'a collapsing of MY fragile scientific awareness wave-function' statement sans sufficient
    smearing à la EPT.

    However, this is s.b.e., and by your statement you seem to *needlessly ignore* that what any target
    cell does with the sensory information it receives is crucially relevant and important if seen in
    context of naturally selective feedback effects generated throughout phylogeny -- i.e. feedback
    effects in the form of deaths and reproductive failures, and survivals and reproductive successes.

    Especially important is what directly motor-action effecting target cells (embedded in a crucially
    opportune or precariously adverse - though not necessarily cliff-edge hanging - life-circumstances)
    do with their received stimuli.

    Even whilst 'doing exact or exacting science' (so to speak) I don't think one should _accEPT_ [that
    is how - by those three swollen-headed letters - I get up some people's noses by referring to my far-
    out formulation of how I think
    %-}] loosing sight of the big picture.

    Apropos which, I can only try to 'assure' you that EPT is one of these BIG [won't protest if you
    think of it is swollen-headed but might try to correct you if you show sign of vaguely believing
    that it is entirely empty-headed ;-)] PICTURES.

    P P
     
  4. A A

    A A Guest

    Simulaneous changes in two different mechanisms was probably once necessary for the pineal gland
    and the brain to start an interaction. Thus, simultaneous mutations occured and a new species
    was created.

    If speciation is a rooted discontinous branching process then there is two fixed numbers that
    together relate any two species.

    Mats Liljedahl

    [email protected] (CNCabej) wrote:

    >On 17 Feb 2004 r norman wrote:
    >
    >>NC
    >
    >>You write: "I have a great deal of difficulty with statements like "the effect of the stimulus is
    >>determined by stereochemical and thermodynamical properties of the stimulus." Let me try to make
    >>it simpler . The spatial configuration of a hormone, and an antibody molecule, must be
    >>complementary to that of a cell membrane receptor,and an antigen (this is a stereochemical
    >>property). But often this may be not sufficient for two molecules to react, if they or their
    >>environment do not possess enough energy that is necessary for that reaction to take place
    >>(e.g., sequential phosphorylation of proteins in signal transduction pathways is necessary for
    >> activation of those pathways).
    >>
    >>You also write: "Pineal gland cells are highly differentiated by whatever developmental processes
    >>produce those cells. As a result, they express the genes involved in melatonin synthesis and are
    >>capable of secreting melatonin. That is what I referred to as "their thing"." But, neither the
    >>type of the cell nor "the thing" tells us anything about the cause of the expression of genes for
    >>melatonin genes in pineal cells (otherwise I would expect you to elaborate on "why" the pineal
    >>cells do what other cells can't). You can't explain an unknown with another. If we could
    >>automatically figure out causes and mechanisms of gene expression by the type of cell this would
    >>make unnecessary or obsolete one of the most important fields of modern biological research.
    >>
    >>Further you write: "In fact, the stimulation of the pineal is through the sympathetic nervous
    >>system. That is, if you drop norepinephrine onto the pineal gland or artificially stimulate the
    >>superior cervical
    >ganglion,
    >>the gland will release melatonin just as effectively as if you stopped shining light into the
    >>eye." I am afraid that this contradicts your previous statements (that no information is needed
    >>for expression of melatonin genes), but I am glad to find something we agree on. If you drop
    >>epinephrine or if you artificially stimulate the pineal cells to synthesize melatonin, you are
    >>able to do this because you know, you have information (in your expression you have "calculated")
    >>that this will activate melatonin genes. A person that has no information could not do it.
    >>Similarly, specific information is needed for specific activation of melatonin genes out of 30,000
    >>genes in billions/trillions of more than 2 hundred types of cells of our body.
    >>
    >>Now let me comment on your next and more encouraging statement. You write "The nervous system
    >>"calculates" only that during daylight it should refrain from sending action potentials to the
    >>superior cervical ganglion destined for the pineal and to resume those action potentials." In
    >>principle, I agree completely with your ideas that
    >>1. the nervous system controls both the activation and inactivation of melatonin genes,
    >>2. that this CNS control is "calculated", in the meaning that the CNS knows when to send and when
    >> to "refrain" from sending its signals for expression of genes for melatonin synthesis Granted
    >> that a "calculated" response implies "information", from the above premises anyone might draw
    >> the logical conclusion that the CNS is the source of the epigenetic information for melatonin
    >> synthesis.
    >>
    >>But the last phrase shows that you still feel not comfortable with your above statement. You
    >>write:"Nowhere does the nervous system calculate just how to activate any specific genes or how to
    >>secrete any specific chemical." I could bring numerous examples proving the contrary. For now let
    >>me just very briefly state that the CNS can express genes that no extracerebral cells can. It does
    >>this by processing information on internal signals (hormones, growth factors) which HAVE NO ACCESS
    >>to the CNS. For example, a stimulus on a drop in the level of estrogen in the blood is perceived
    >>and processed in a specific neural
    >
    >>circuit. The chemical output of the processing (not the estrogen) of that stimulus via projections
    >>of the neurons of that circuit on specific hypothalamic cells triggers the expression of the GnRH
    >>(gonadotropin releasing hormone). This response is not determined by the stereochemical and
    >>thermodynamical properties but from the processing (computational process) of the stimulus in the
    >>respective
    >neural
    >>circuit. This is the reason why in nonneural cells the estrogen activates compeltely
    >>different genes.
    >>
    >>P.S. as for your statement that "computational properties of neurons have nothing whatsoever to do
    >> with" the secretion of melatonin, this is hardly compatible with the predominant opinion of
    >> researchers that CNS responses are determined by computational properties of respective
    >> neural circuits, and those properties change in response to various internal and external
    >> stimuli.
    >>
    >R. N. We are still far apart but maybe converging.
    >
    >Of course there is a sense of "information transfer" in all cell signaling, including the binding
    >of a hormone or neurotranmitter to its receptor and the subsequent downstream pathway. Of course
    >there is a sense of "information transfer" in the developmental process.
    >
    >It was my impression that you were trying to say that somehow neural circuits code "code
    >information" for "turn on melatonin synthesis". I am simply saying that the pattern of neural
    >connectivity automatically connects certain photosensitive cells to the sympathetic system. The
    >nervous system computes something like "tell the pineal to go" or "don't tell the pineal to go".
    >What the pineal does with that signal (sympathetic activation) is something "coded" into the pineal
    >gland, not into neural computation.
    >
    >Yes, CNS cells can express specific genes and they can be induced to do so by stimuli or by
    >hormones that never enter the CNS. Clearly what happens is that such stimuli are acting on sense
    >organs that send action potentials into the CNS. The post-synaptic signaling pathway in specific
    >CNS cells may well have the ability to activate genes -- the CREB system is a good example. My
    >impression was that you were saying something like action potentials "code information" to
    >"activate this specific gene." What I am saying is the the neural information coded is simply "I
    >got this stimulus". What the target cell does with that information is totally irrelevant to the
    >sensory system that detected the stimulus.
    >
    >N.C.
    >
    >First, I am glad we agree that a transfer of information generated in a specific circuit of the CNS
    >is transmitted to the pineals cells. As for the nature of this information, it is essential to
    >point out that
    >
    >-this is different from the genetic information contained in genes in the form of nucleotide
    >sequences determining the sequence of amino acids in RNA and polypeptides.
    >
    >-the information that is sent to pineal cells does not preexist in the brain structure, but it is
    >generated in the specific neural circuit, by processing the external stimulus. Being a result of a
    >computational process (and having nothing to do with the sequence of nucleotides in DNA), this is
    >information is EPIGENETIC.
    >
    >-this epigenetic information is necessary for expression of melatonin genes in the pineal cells,
    >i.e. controls their expression (in your expression, the nervous system computes something like
    >"tell the pineal to go" or "don't tell the pineal to go")
    >
    >I have difficulty in agreeing with you that "the neural information coded simply "I got this
    >stimulus". What does the target cell do with that information is totally irrelevant to the sensory
    >system that detected the stimulus."
    >
    >This is indefensible in view of the facts that
    >1) the neural circuit sends a "computed" signal that specifically (not randomly) activates a
    > specific signal transduction pathway, which makes possible expression of melatonin genes. At
    > this point there is no choice for pineal cells; the expression of melatonin genes is
    > unavoidable, predetermined by the epigenetic information those cells receive.
    >
    >2) The neural circuit not only generates the information for activation of melatonin genes, but it
    > "knows" to exactly address that information to a certain type of cell (out of more than 2
    > hundred cell types) of a mammal), the only cells capable of producing melatonin, .
    >
    >Finally, I am interested to know more about your idea that such information transfer takes place in
    >the developmental process.
     
  5. John Edser

    John Edser Guest

    > JE:- This means that any supposed epigenetic inheritance (the inheritance of a controlling
    > substance to a joint sub system above the gene level) can in principle, control the rigidity
    > /flexibility of this jointly selected sub system within the same fertile form. This means the
    > _total_ amount of melatonin per unit time and the way this effects diverse other sub systems and
    > the flexibility or otherwise of this melatonin secretion as is controlled by the said sensory
    > system is as a whole is potentially controllable via an epigenetic form of inheritance. To my
    > knowledge no
    such
    >system has been identified in this specific case.

    NC:- I agree with you that from a single case of epigenetic control of the expression of melatonin
    genes in the pineal cells one may not conclude the existence of the epigenetic system of inheritance
    predicted already by
    J.Maynard Smith. But would you agree with me that the existence of an epigenetic system of
    inheritance could not be reasonably denied if
    1. The epigenetic control of the expression of nonhousekeeping genes proves to be a general mode of
    expression of (nonhousekeeping) genes in the CNS, and
    2. The expression of nonhousekeeping genes in extraneural cells is epigenetically regulated by
    signals from the CNS?

    JE:- I agree that the CNS can control gene expression. However, that is different to suggesting that
    the CNS provides a verified heritable epigenetic platform from which to do this. The problem is that
    very little will seems to exist to explore such a possibility. Can the CNS provide substances that
    can move into egg and/or sperm cells that could alter, when, by how much, and which genes are
    expressed within each offspring? It seems to me that such substances, if they existed, would be of
    enormous benefit and would most probably be proteins. Because proteins can be coded by DNA/RNA does
    not mean that they cannot be regarded as epigenetic in their own right. Such a epigenetic system
    would act something like Darwin's pangenes. Substances that control gene expression that have been
    fine tuned to the parental environment could be passed on to offspring who are born and develop
    already fine tuned to the immediate parental environment in which they will probably find
    themselves, giving them a selective edge. In some species the primordial germ cells Of course this
    does not stop these offspring doing their own fine tuning and passing this on to their offspring.
    Heritable epigenetic control systems would mostly remain much more flexible than genetic control
    systems because immediate environments can quickly change. It seems reasonable to suppose that the
    more rigid genetic system working alongside a more flexible epigenetic system allows much more
    efficient long and short term adaptation.

    Respectfully,

    John Edser Independent Researcher

    PO Box 266 Church Pt NSW 2105 Australia

    [email protected]
     
  6. CNCabej

    CNCabej Guest

    On Feb 23 J.Edser wrote:>NC:-
    >I agree with you that from a single case of epigenetic control of the expression of melatonin genes
    >in the pineal cells one may not conclude the existence of the epigenetic system of inheritance
    >predicted already by
    >J.Maynard Smith. But would you agree with me that the existence of an epigenetic system of
    > inheritance could not be reasonably denied if
    >1. The epigenetic control of the expression of nonhousekeeping genes proves to be a general mode of
    > expression of (nonhousekeeping) genes in the CNS, and
    >2. The expression of nonhousekeeping genes in extraneural cells is epigenetically regulated by
    > signals from the CNS?
    >
    >JE:- I agree that the CNS can control gene expression. However, that is different to suggesting
    >that the CNS provides a verified heritable epigenetic platform from which to do this. The problem
    >is that very little will seems to exist to explore such a possibility. Can the CNS provide
    >substances that can move into egg and/or sperm cells that could alter, when, by how much, and which
    >genes are expressed within each offspring? It seems to me that such substances, if they existed,
    >would be of enormous benefit and would most probably be proteins. Because proteins can be coded by
    >DNA/RNA does not mean that they cannot be regarded as epigenetic in their own right. Such a
    >epigenetic system would act something like Darwin's pangenes. Substances that control gene
    >expression that have been fine tuned to the parental environment could be passed on to offspring
    >who are born and develop already fine tuned to the immediate parental environment in which they
    >will probably find themselves, giving them a selective edge. In some species the primordial germ
    >cells Of course this does not stop these offspring doing their own fine tuning and passing this on
    >to their offspring. Heritable epigenetic control systems would mostly remain much more flexible
    >than genetic control systems because immediate environments can quickly change. It seems reasonable
    >to suppose that the more rigid genetic system working alongside a more flexible epigenetic system
    >allows much more efficient long and short term adaptation.

    While you agree that the CNS can control gene expression (and I expect you also to agree that it
    DOES that), you question whether this epigenetic control might represent a general mechanism of gene
    expression in metazoans.

    My answer would be "Yes", but I know I need to elaborate on this and I will within the limits of
    this newsgroup.

    As we all know, from 10-30,000 genes of the metazoan genome, several thousands, the so-called
    HOUSEKEEPING GENES, are needed for the subsistence and reproduction of metazoan cells and are
    expressed some time during the lifetime of the cell. The rest, i.e. the majority of them are
    NONHOUSEKEEPING GENES, which perform extracellular, organismic functions and are expressed
    differentially in different types of cells. Their extracellular function determines the
    extracellular origin of signals for their expression, for no cell could figure out what the organism
    might need at any particular point in time (cell-cell interactions come to mind but they will later
    be dealt with).

    But the extracellular signals (protein- and nuclear hormones, growth factors, other secreted
    proteins and even neuropeptides, neurotransmitters and neuromodulators) are themselves produced in
    response to upstream signals (hormones of the target endocrine glands in the case of growth
    factors). For almost a century it is known that those glands produce their hormones in response to
    specific hormones produced by the pituitary that was considered to be the "master gland". After 50-
    60es of the last century biologists have shown that the pituitary, as well, synthesizes each of its
    hormones in response to a specific "releasing" hormone produced by a part of the brain, the
    hypothalamus. During the last two decades evidence is accumulating that shows that the signal
    cascade for expression of the hypothalamic genes starts still higher (or deeper) in the brain with
    the chemical output (signals) that neural circuits produce by processing (a computational,
    nongenetic process) of interna/external stimuli.

    This mechanism of gene activation in the CNS makes possible a flexible and manipulative expression
    of genes that could otherwise not be expressed. The need for this manipulative expression of genes
    might have determined the evolution of blood-brain barrier; the CNS does not need to have contact
    with most of the circulating signal molecules. What it needs is information on the presence and/or
    level of the signal molecules (the pervasive presence of the neural tissue in the body allows
    this) which is used to "calculate" the necessary response, that is release of a chemical signal
    that leads to the expression of a gene that the signal. molecule itself can not express. So, e.g.
    a the estradiol does not have access to the hypothalamus, but a change in its level is
    "perceived'" by the CNS, which by processing this stimulus makes possible expression of the GnRH
    gene (not genes that it activates in nonneural cells, such as cyclin D, IGF-1 etc.). This is
    clearly a manipulative expression of genes that is made possible by the processing of a stimulus
    in a specific neural circuit.

    I admit that by showing that epigenetic information generated in the CNS regulates gene expression
    we have not proven the existence of what you call "heritable epigenetic platform" for as you point
    out, this would require the CNS to "provide substances that can move into the egg and/or sperm cells
    that could alter, when, by how much, and which genes are expressed within each offspring."

    What we need to demonstrate is that all the stages of animal reproduction, starting with the
    formation of gametes and individual development are under the CNS control and regulation.

    Adequate experimental evidence already shows that the CNS (to be more exact, the integrated control
    system, which besides the CNS comprises the mechanisms for monitoring the status of the living
    system in general as well as the pathways for transmission to the cells all over the animal body of
    the epigenetic information generated in neural circuits) controls and regulates:

    1. The formation of the egg and sperm cells

    2. The placement of maternal cytoplasmic factors in the egg cell.

    3. The early embryonic development (which is regulated not by zygotic genes, but by maternal
    cytoplasmic factors) up to the phylotypic stage, when a functioning CNS first arises.

    4.The postphylotypic development, including the post-natal development (the
     
  7. John Edser

    John Edser Guest

    >JC;- I agree with you that from a single case of epigenetic control of the expression of melatonin
    >genes in the pineal cells one may not conclude the existence of the epigenetic system of
    >inheritance predicted already by
    >J.Maynard Smith. But would you agree with me that the existence of an epigenetic system of
    > inheritance could not be reasonably denied if
    >1. The epigenetic control of the expression of nonhousekeeping genes proves to be a general mode of
    > expression of (nonhousekeeping) genes in the CNS, and
    >2. The expression of nonhousekeeping genes in extraneural cells is epigenetically regulated by
    > signals from the CNS?

    >JE:- I agree that the CNS can control gene expression. However, that is different to suggesting
    >that the CNS provides a verified heritable epigenetic platform from which to do this. The problem
    >is that very little will seems to exist to explore such a possibility. Can the CNS provide
    >substances that can move into egg and/or sperm cells that could alter, when, by how much, and which
    >genes are expressed within each offspring? It seems to me that such substances, if they existed,
    >would be of enormous benefit and would most probably be proteins. Because proteins can be coded by
    >DNA/RNA does not mean that they cannot be regarded as epigenetic in their own right. Such a
    >epigenetic system would act something like Darwin's pangenes. Substances that control gene
    >expression that have been fine tuned to the parental environment could be passed on to offspring
    >who are born and develop already fine tuned to the immediate parental environment in which they
    >will probably find themselves, giving them a selective edge. In some species the primordial germ
    >cells Of course this does not stop these offspring doing their own fine tuning and passing this on
    >to their offspring. Heritable epigenetic control systems would mostly remain much more flexible
    >than genetic control systems because immediate environments can quickly change. It seems reasonable
    >to suppose that the more rigid genetic system working alongside a more flexible epigenetic system
    >allows much more efficient long and short term adaptation.

    JC:- While you agree that the CNS can control gene expression (and I expect you also to agree that
    it DOES that), you question whether this epigenetic control might represent a general mechanism of
    gene expression in metazoans.

    My answer would be "Yes", but I know I need to elaborate on this and I will within the limits of
    this newsgroup.

    As we all know, from 10-30,000 genes of the metazoan genome, several thousands, the so-called
    HOUSEKEEPING GENES, are needed for the subsistence and reproduction of metazoan cells and are
    expressed some time during the lifetime of the cell. The rest, i.e. the majority of them are
    NONHOUSEKEEPING GENES, which perform extracellular, organismic functions and are expressed
    differentially in different types of cells. Their extracellular function determines the
    extracellular origin of signals for their expression, for no cell could figure out what the organism
    might need at any particular point in time (cell-cell interactions come to mind but they will later
    be dealt with).

    JE:- OK

    JC:- But the extracellular signals (protein- and nuclear hormones, growth factors, other secreted
    proteins and even neuropeptides, neurotransmitters and neuromodulators) are themselves produced in
    response to upstream signals (hormones of the target endocrine glands in the case of growth
    factors). For almost a century it is known that those glands produce their hormones in response to
    specific hormones produced by the pituitary that was considered to be the "master gland". After 50-
    60es of the last century biologists have shown that the pituitary, as well, synthesizes each of its
    hormones in response to a specific "releasing" hormone produced by a part of the brain, the
    hypothalamus. During the last two decades evidence is accumulating that shows that the signal
    cascade for expression of the hypothalamic genes starts still higher (or deeper) in the brain with
    the chemical output (signals) that neural circuits produce by processing (a computational,
    nongenetic process) of interna/external stimuli.

    JE:- OK. Epigenetic control hierarchies exist which may be much larger within metazoan forms such
    that they can alter the phenotype expressed from the same set of genes.

    In the diagrams below I have indicated the genetic system (box G) connected to two epigenetic
    systems boxes E and E1. The genes code for just a 0 range but the epigenetic systems can allow a
    maximal extension the range of expression of that phenotype to +1 or -1. I have shown that the
    extreme phenotype of -1 only has one G-->E -->E1 configuration. Obviously only one such
    configuration also exists for +1.

    Fig 1. Extreme -1 phenotype.

    --|+1
    |
    |
    |
    |
    |
    |
    +---+ --0
    | G | |
    +---+\ | \ +---+ | \ | E | | +---+\ | \ +---+ | \|E1 | --|-1 +---+

    Given the position of E, E1 the phenotype can only range between 0 and -1. Thus if the position of E
    but not E1 was epigenetically inherited then exactly the same genes could produce a phenotype now
    ranging from 0 to -1. However if E was inherited in its mmaximal position above G and not below it,
    then exactly the same genes would range from 0 to +1.

    Fig 2. An alternative gene coded phenotype range of 0.

    -- +1
    |
    |
    +---+ | /| E | | / +---+\ | +---/ \ +---+ | |G | \| E1| -- 0 +---+ +---+
    |
    |
    |
    |
    |
    -- -1

    Here the positions of E and E1 contradict each other only allowing the genes to be expressed
    within range 0.

    Clearly, many more phenotypes can be expressed using epigenetics than can be expressed just using
    genes. The greater the number of sequentially linked epigenetic boxes the more complex the range of
    phenotype expression.

    I don't think the above is controversial. What is, is the supposition that E and E1 can be
    inherited. In fig 1, if E and E1 are inherited in that exact position then the phenotype range would
    be restricted to -1. Obviously, using the opposite configuration it would be fixed to +1.

    JC:- This mechanism of gene activation in the CNS makes possible a flexible and manipulative
    expression of genes that could otherwise not be expressed.

    JE:- OK

    JE:- The need for this manipulative expression of genes might have determined the evolution of blood-
    brain barrier; the CNS does not need to have contact with most of the circulating signal molecules.
    What it needs is information on the presence and/or level of the signal molecules (the pervasive
    presence of the neural tissue in the body allows this) which is used to "calculate" the necessary
    response, that is release of a chemical signal that leads to the expression of a gene that the
    signal. molecule itself can not express. So, e.g. a the estradiol does not have access to the
    hypothalamus, but a change in its level is "perceived'" by the CNS, which by processing this
    stimulus makes possible expression of the GnRH gene (not genes that it activates in nonneural cells,
    such as cyclin D, IGF-1 etc.). This is clearly a manipulative expression of genes that is made
    possible by the processing of a stimulus in a specific neural circuit.

    I admit that by showing that epigenetic information generated in the CNS regulates gene expression
    we have not proven the existence of what you call "heritable epigenetic platform" for as you point
    out, this would require the CNS to "provide substances that can move into the egg and/or sperm cells
    that could alter, when, by how much, and which genes are expressed within each offspring."

    JE:- I think that proving a heritable epigenetic platform exists is the next step. Prions and known
    heritable epigenetic effects in the cortex of protists studied by Sonniborn have set the stage.

    JC:- What we need to demonstrate is that all the stages of animal reproduction, starting with the
    formation of gametes and individual development are under the CNS control and regulation.

    JE:- I think you are arguing that the CNS is the last (highest) epigenetic system that exists so
    that it has the power of direction of the phenotype. In my diagram this means the CNS would be E2
    where E2 is limited by E1 and E1 is limited by G.

    JC:- Adequate experimental evidence already shows that the CNS (to be more exact, the integrated
    control system, which besides the CNS comprises the mechanisms for monitoring the status of the
    living system in general as well as the pathways for transmission to the cells all over the animal
    body of the epigenetic information generated in neural circuits) controls and regulates:

    1. The formation of the egg and sperm cells

    2. The placement of maternal cytoplasmic factors in the egg cell.

    3. The early embryonic development (which is regulated not by zygotic genes, but by maternal
    cytoplasmic factors) up to the phylotypic stage, when a functioning CNS first arises.

    4.The postphylotypic development, including the post-natal development (the

    JE:- Could you provide one example of each of the above?

    Respectfully,

    John Edser Independent Researcher PO Box 266 Church Pt NSW 2105 Australia

    [email protected]
     
  8. CNCabej

    CNCabej Guest

    On Fri, 27 Feb 2004 16:40:59 +0000 (UTC) John Edser" [email protected] wrote

    NC:-
    >As we all know, from 10-30,000 genes of the metazoan genome, several thousands, the so-called
    >HOUSEKEEPING GENES, are needed for the subsistence and reproduction of metazoan cells and are
    >expressed some time during the lifetime of the cell. The rest, i.e. the majority of them are
    >NONHOUSEKEEPING GENES, which perform extracellular, organismic functions and are expressed
    >differentially in different types of cells. Their extracellular function determines the
    >extracellular origin of signals for their expression, for no cell could figure out what the
    >organism might need at any particular point in time (cell-cell interactions come to mind but they
    >will later be dealt with).
    >
    >JE:- OK

    >NC:-
    .........................................................
    >JE:- OK. Epigenetic control hierarchies exist which may be much larger within metazoan forms such
    >that they can alter the phenotype expressed from the same set of genes.
    >

    Thus, you agree that the expression of nonhousekeeping genes, which are responsible for cell
    differentiation and cell-cell interactions, is under epigenetic (NONGENETIC) control. In view of the
    fact that all the stages of metazoan reproduction (gametogenesis, early development and
    organogenesis) depend on cell differentiatiion, it follows that this epigenetic system, or these
    "epigenetic control hierarchies", regulates the individual development in metazoans.

    >NC:- What we need to demonstrate is that all the stages of animal reproduction, starting with the
    >formation of gametes and individual development are under the CNS control and regulation.
    >
    >JE:- I think you are arguing that the CNS is the last (highest) epigenetic system that exists so
    >that it has the power of direction of the phenotype. In my diagram this means the CNS would be E2
    >where E2 is limited by E1 and E1 is limited by G.
    >

    I would rather say that there is one integrated control system, with the CNS as its controller that
    is limited by genes (G), as well by numerous external and internal stimuli.

    >JC:- Adequate experimental evidence already shows that the CNS (to be more exact, the integrated
    >control system, which besides the CNS comprises the mechanisms for monitoring the status of the
    >living system in general as well as the pathways for transmission to the cells all over the animal
    >body of the epigenetic information generated in neural circuits) controls and regulates:
    >
    >1. The formation of the egg and sperm cells
    >
    >2. The placement of maternal cytoplasmic factors in the egg cell.
    >
    >3. The early embryonic development (which is regulated not by zygotic genes, but by maternal
    > cytoplasmic factors) up to the phylotypic stage, when a functioning CNS first arises.
    >
    >4.The postphylotypic development, including the post-natal development (the

    >
    >JE:- Could you provide one example of each of the above?
    >

    "One example of each of the above" is a reasonable challenge, even though examples abound.

    >1. The formation of the egg and sperm cells

    a. In the female fire ant, Solenopsis invicta, the electrical activation of the dopamine system
    resulting fromthe PROCESSING of an external stimulus (queen pheromone) in the brain controls
    oogenesis and oviposition (Boulay et al 2000).
    b. For more than two decades it is generally acknowledged that spermatogenesis "is ultimately
    controlled by neurons in the CNS" (Sharp and Gow 1983) and that the CNS exerts that control via
    the GnRH pulse generator and the hypothalamic-pituitary-testicular axis (Vander).

    >2. The placement of maternal cytoplasmic factors in the egg cell.

    In the canary, Serinus canaria, the seasonal changes of photoperiod are processed in the brain and
    via hypothalamic-pituitary-ovarian axis determine the concentration of maternal testosterone in the
    egg (Schwabl, 1993).

    >3. The early embryonic development (which is regulated not by zygotic genes, but by maternal
    > cytoplasmic factors) up to the phylotypic stage, when a functioning CNS first arises.

    Since -the parental CNS regulates the placement of maternal cytoplasmic factors in the egg cell, and
    -maternal cytoplasmic factors regulate the early development (Wolpert et al 1998; Hall 1998; Gilbert
    2000, etc etc.)

    -THE PARENTAL CNS(s) REGULATE THE EARLY DEVELOPMENT (since A regulates B and B regulates C)

    >4.The postphylotypic development, including the post-natal development (the

    During embryogenesis the sensory neurons and Schwann cells secrete VEGF, which determines the cell
    differentiation and patterning of arteries in their vicinity what explains the old anatomic
    observation on the general association of arteries and peripheral nerves (Mukoyama et al. 2002).

    One more example. For a long time it has been believed that the expression of the Sry gene on the
    chromosome Y induces the development of testes and hormones secreted by testes determine the
    specific organization of the male

    differentiation of the brain starts before the expression of the Sry gene on the chromosome Y,
    before the testes are formed and testosterone is secreted (Dewing et al 2003). Recently (2003) in
    the Proc.Natl. Acad. Sci. USA, a naturally occurring zebra finch was reported to be male (with
    testis) on the right side and female (with an ovary) on the left, although genes and the circulating
    hormones are the same in both sides. Only brain circuits on the right side are of different male
    patterning.

    I believe the epigenetic system of heredity in metazoans is an obvious reality. The examples
    presented here and numerous others clearly show that the expression of nonhousekeeping genes and the
    main stages of individual development are under control of an epigenetic control predicted by J.
    Maynard Smith.

    Thank you for giving me the opportunity to argue and substantiate the existence of this system.
    Further input and critical remarks from you, r. norman, and others in the sbe are wellcomed and
    appreciated.
     
  9. Peter F.

    Peter F. Guest

    "CNCabej" <[email protected]> wrote in message
    news:[email protected]...
    > I would rather say that there is one integrated control
    > system, with the
    CNS as
    > its controller that is limited by genes (G), as well by
    > numerous external
    and
    > internal stimuli.

    I think that what you are expounding fits in somewhere at
    the center of the most interesting and fascinating of all
    fields of scientific inquiry.

    (It makes me salivate without being able to chew and swallow
    - but I still love it from a distance.;)

    However, even if the notion and embryonic theory of "the
    histone code" might currently not catalyze conceptual
    clarity or inspire further insight, I still think it is
    generally so relevant to what is discussed here that you
    ought to have at least given it a mention.

    If only for sake of a good (comprehensively spread-
    out) measure.

    P
     
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