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Gene expression is under epigenetic control (Was: Epigenetic information

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General fitness, health and nutrition
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9 March 2004
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9 March 2004
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John Edser
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  1. NC:-

    Quoted message said:

    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).

    Quoted message said:

    JE:- OK

    Quoted message said:

    NC:-


    .........................................................

    Quoted message said:

    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.

    NC (is NC you correct initials?): Thus, you agree that the
    expression of nonhousekeeping genes, which are responsible
    for cell differentiation and cell-cell interactions, is
    under epigenetic (NONGENETIC) control.

    JE:- Yes. Note however that epigenetic products are
    ultimately coded for by genes. "Everything" can be reduced
    to just genes when reductive reasoning (deduction) is
    misused. This is something like reducing a work of
    Shakespeare to just a word count. When you do this, 99% of
    the information is deleted. What you are fighting against is
    the reductive view that we are just the sum of our genes.

    NC:- 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.

    JE:- It is a classical "chicken and egg" argument. The CNS
    regulates genes but genes code for the CNS. So what came
    first, the genes or the CNS? The answer is neither. They
    evolved _together_ within a _single_ unit of selection.

    Epigenetic systems of inheritance have been documented
    within nature. The problem is, how do you experimentally
    separate out Mendelian gene inheritance from an epigenetic
    level of inheritance? Classical analytical genetics will
    just "see through" any proposed epigenetic level to only
    resolve the most basic level: the gene. Epigeneticists will
    have to readjust their deductive microscopes to only resolve
    a low power of magnification.

    Quoted message said:

    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

    Quoted message said:

    the CNS control and regulation.

    Quoted message said:

    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.

    NC:- 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.

    JE:- Ok. I attempt to illustrate this in the following way:-

    selective forces
    |
    V
    +-----------------------------+
    selective | | selective
    forces ---> | genes --->epigenes---->CNS | <--- forces
    | |
    | |
    +-----------------------------+
    ^
    |

    selective forces

    The box represents a single Darwinian unit of selection (one
    fertile form). Selective forces surround it,
    i.e. they act on every level within the box strictly
    however, at just the one level of selection which the
    dotted line of the box represents: one fertile form.

    Within each fertile form genes can only limit epigenes and
    likewise, epigenes can only limit the CNS which is here,
    supposed as the highest (most complex) epigenetic level
    within each Darwinian form. Any deduction from the CNS must
    end up with just, genes. The reductionist "misses" the other
    two levels by "seeing through" them. Inductive theory
    building sees in the direction of the arrows within each
    independently selected box but analytical deductive theory
    can only see against the arrows. Epigenes become the meat in
    the sandwich because they control gene expression but at the
    same time limit CNS action. In this respect they may be
    missed by both reductive and inductive investigation.

    Quoted message said:

    NC:- Adequate experimental evidence already shows that the
    CNS (to be more


    exact,

    Quoted message said:

    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,

    Quoted message said:

    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

    Quoted message said:

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

    NC:- "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
    from the PROCESSING of an external stimulus (queen
    pheromone) in the brain controls oogenesis and
    oviposition (Boulay et al 2000).

    JE:- It would be interesting to find out if the activation
    of this dopamine system could be preactivated by epigenetic
    inheritance of queen pheromone.

    NC:-
    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).

    Quoted message said:

    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).

    Quoted message said:

    3. The early embryonic development (which is regulated not
    by zygotic


    genes,

    Quoted message said:

    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)

    Quoted message said:

    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.

    JE:- Thank you for your scholarly discourse. However for the
    gene centrics that dominate this site most will just falsely
    conclude that in the end, it is all just reducible to genes.

    I agree that "the epigenetic system of heredity in metazoans
    is an obvious reality" but proving the obvious is no easy
    task but remains, essential. Nobody seems to be interested
    in attempting to measure epigenetic inheritance because the
    genetic component of it (which has to exist) must be
    entirely removed within a properly controlled experiment.
    Indeed, prejudice against investigating epigenetic systems
    within evolutionary theory because of ancient echoes of
    Lamarck's "acquired characters", remains so enormous that it
    seems to me that researchers are going out of their way to
    avoid observing any epigenetic heritability in the dire fear
    of being labelled a Lamarckian heretic and having their
    research grants stopped.

    Genes remain today's new toys and not epigenes. I think a
    good strategy would be to create a hot list of documented
    heritable epigenetic events and post it to sbe for comment.

    Respectfully,

    John Edser Independent Researcher

    PO Box 266 Church Pt NSW 2105 Australia

    [email hidden]

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