633 lines
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633 lines
50 KiB
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<head><title>Estrogen, memory and heredity: Imprinting and the stress response</title></head>
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<h1>
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Estrogen, memory and heredity: Imprinting and the stress response
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</h1>
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<p>
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<hr />
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IN OUTLINE: Stresses, including estrogen excess, activate the Heat Shock Proteins (HSP), the
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stress-proteins, a primitive defense system. Heat Shock Proteins and "hormone receptors" are closely related
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and interdependent. Stress (at least partly via HSP) activates viral expression, ordinary gene expression,
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and destabilizes the genome, activating the "endonucleases," enzymes which break up DNA chains. Stress
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increases genetic variability. DNA chains can be chemically modified (e.g., methylated) in a way that limits
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enzymes' accesss, probably as protection, and to regulate gene expression. Genes, and subsequent growth and
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development, are modified by the prenatal hormonal environment, that of the newborn, and even that of the
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parents before conception.
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<em>Genomic imprinting</em> makes maternal genes behave differently from paternal genes.
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<em>Hormonal imprinting</em> early in life sets the pattern of expression of genes. "Crossing-over"
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intermixes the genes on the chromosomes as cells multiply. Stresses and regulatory substances can change the
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patterns of gene expression that define cell types. "Stem cells" are those capable of renewing tissues, and
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may be "pluripotent," able to become glial cells and neurons in the brain, or, in the bone marrow, to become
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red blood cells or white blood cells, depending on regulatory influences. "Cloning" animals from body cells
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strongly suggests that any cell is potentially totipotent, able to differentiate into any other type of
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cell. We are "imprinted" by our mothers' hormonal and nutritional conditions, but we can intervene to
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correct these "inherited" conditions, by maintaining optimal hormonal and nutritional balances.
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<hr />
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Recent work in several areas of biology is showing that heredity is not rigidly deterministic, in the way
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implied by traditional genetics, and it is opening the way for the development of therapies for incurable,
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chronic, or congenital problems, <em>in natural and holistic ways that don't involve the mechanistic
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interventions of "gene therapy" or "genetic engineering."
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</em> For example, nontoxic treatments for cancer that were demonstrated decades ago, were discarded because
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they didn't seem consistent with "genetics." Many problems that are classified as congenital or genetic,
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turn out to be physiological, and correctable. Even the brain and the heart, which until recently were
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considered to be incapable of regenerative repair, are now seen to be capable of great anatomical
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flexibility.
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</p>
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<p>
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There are still great authoritarian forces opposed to recognizing, and supporting, the organism's full
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potential. <strong>The most useful therapies will remain in obscurity until many people see that those
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therapies have a firmer scientific foundation than orthodox (antiquated) medical genetics has.
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</strong>Over 100 years ago, Samuel Butler had an argument with Charles Darwin, and concluded that Darwin
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was philosophically muddled, and dishonest. Butler was annoyed that Darwin had belittled the work of his
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predecessors, including his grandfather, Erasmus Darwin. Butler was defending the idea of biological
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intelligence, the incorporation of experience into physiology and heredity.
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</p>
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<p>
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My parents had an old copy of one of Darwin's books, and I was impressed by the fact that in his
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introduction, Darwin was careful to point out that <em>his ideas were already being misrepresented, and that
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he did not hold "natural selection" to be the only mechanism of evolution,</em>
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but that several factors were important, including sexual selection and the inheritance of acquired traits.
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I suppose those remarks might have been motivated partly by knowing that Butler didn't approve of the way he
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was behaving, but they didn't seem to have much influence on the way history has characterized Darwin's
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work. All of my biology professors would have been happier if Darwin had never made those remarks. I suspect
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that Darwin's problem was that <em>any theory of evolution </em>
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was under such heavy attack that he couldn't devote much time to the relatively minor issue of how evolution
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works. After Darwin's death, the study of heredity made some strange concessions to the culture of
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anti-evolutionism. As people began thinking about "particles that carry heredity," the "genes," ideas from
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the anti-evolutionist culture formed much of the context for understanding these "particles."
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</p>
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<p>
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Darwin had suggested that the mature organism reconstitutes itself in the germ cells, by sending gemmules or
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pangens (buds or sprouts or derivatives) from its various parts, so that the parent's traits would be
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incorporated into the reproductive cells. This was called pangenesis, meaning that the whole organism was
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the source for the new offspring. This theory opened the possibility for newly acquired traits to be passed
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on. It grew out of the experience of animal breeders and horticulturists, who were dedicated to improving
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their breeds and strains, <em>by selecting the best individuals grown under the best conditions.
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</em> It was known that the miniature ponies, <strong>Shetlands for example, would grow larger each
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generation when bred under favorable conditions of domestication, rather than under the harsh conditions
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of their native island.
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</strong> It apparently never occurred to most plant and animal breeders that they might be able to <em
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>improve</em> a breed by subjecting it to harmful conditions. Around the end of the 19th century, August
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Weismann began a systematic attack on the ideas of Darwin. As part of his campaign, he invented the doctrine
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that the reproductive cells are absolutely isolated from the rest of the organism, and that they are
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immortal. The rest of the organism is built up by the <em>deletion</em> of genetic information. This
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doctrine was very convenient for those who maintained that all organisms had been created in a single
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moment, and that the <em>appearance</em>
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of evolution resulted from the extinction of some species, but not the new appearance of some species. Some
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people, reasoning from Weismannism, suggested that evolution might have resulted without any change in the
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immortal genetic material, except deletion, in a manner analogous to Weismann's theory of the developing
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individual. Bacteria, in that view, would contain all the genes needed to make a tree or a person, and the
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more complex forms would have evolved through the differential loss of that primeval genetic information.
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</p>
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<p>
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The changes produced by <em>subtraction</em> were compatible with the notion of fallen man in a corrupt
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world, while the <em>addition</em> of heritable traits through experience would connote a sharing in the
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process of creation. The hereditary particles making up Weismann's "immortal isolated germ line" connoted a
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single original creation.
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</p>
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<p>
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As mutations in the genes came to be seen as a reality, experiments with X-rays suggested to some that all
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mutations were harmful, and this attitude blended into the stream of doctrine which insisted that no <em>
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improvement</em> could be inherited. Although many experiments showed what seemed to be meaningfully <em
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>directed</em> mutations, the doctrine held its ground, as its advocates taught that mutations were always
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random. (The doctrine of random change, like the idea that entropy only increases, excluded acts of creation
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from the fallen material world.) If a new trait appeared under new conditions, it was said to be <em>only
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because an old trait was being revealed by the induced loss</em> of another trait.
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</p>
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<p>
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I think anyone who reads the "landmark publications" in genetics will see that genetics had very little to
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do with scientific method, as commonly conceived, and that it had all the traits of a cult. Analysis of the
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language of genetics reveals that terms have more often been used to cover up empty speculation than to
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clarify situations of fact.
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</p>
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<p>
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Parallel to the way Darwin infuriated Samuel Butler by misrepresenting the origins of his theory, the
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neodarwinists who debate the creationists over school textbooks are ignoring the ways in which the culture
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of antievolutionism shaped their own view of genetics. The discovery of enzymes that produce DNA modeled on
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RNA, "reverse transcriptases," began undermining traditional genetics, because it showed that new
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information can enter our genome. The discovery that bacteria can pass "genes" from one individual to
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another, conferring antibiotic resistance upon previously sensitive strains, was a major nuisance to people
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working in infectious disease, since it complicates the treating of disease, but it indicated that
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"evolution," or genetic change, was capable of happening in non-random ways. Early in the study of viral
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genetics, many people realized that "organisms" which can't reproduce without their relatively complex
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hosts, presented a problem for evolutionary theory. If the virus requires a cell in order to exist, it is
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hardly a separate organism. A few people suggested that viruses were, or were based on, functional normal
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parts of higher organisms. Some researchers have suggested that virus-like particles serve to carry
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information from one part of an organism to other parts of that organism. Mobile genetic elements are now
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well recognized, operating within cells, and it is common laboratory practice to use viral particles to
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transfer genetic material from one cell to another.
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</p>
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<p>
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Cellular systems which cut and splice nucleic acids, creating sequences of information which don't exist in
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the inherited chromosomes, are now accepted parts of cell biology. Hormonal and environmental influences on
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the stability of messenger RNA, and on mobile genetic elements, and on genomic stability in general, are
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recognized. <strong><em>The center of gravity in the study of the nucleic acids has now shifted from
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heredity to development.
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</em>Almost nothing remains of Weismannism, which was the foundation of neodarwinism. The "isolation of
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the germline" doctrine persists in a few places, such as explaining why "the ovary runs out of eggs,"
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despite some examples of egg-cell renewal.</strong>
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</p>
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<p>
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<strong>
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But when the identity of "germline cells" is found to depend on signals from the environment, the last
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vestige of Weismannian germ-line doctrine disappears.</strong> The only meaning of "germline" is that
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some cells are destined to be germ cells, and the meaning disappears when such cells differentiate to form
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body parts. (see Donovan, 1998, Labosky, et al., 1994.)
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</p>
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<p>
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The difference between primordial germ cells and embryonic cells is a matter of "imprinting," the process in
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which a hormone or "growth factor" or other "signal" directs a cell down a certain course of
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differentiation. "Imprinting" is where genetics and physiology, phylogeny and ontoneny, come together, and
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the new facts that are being discovered are removing the last vestige of scientific content from
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Weismannism/neodarwinism. The argument between Peter Duesberg and the virus establishment, in which Duesberg
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argues that acquired immunodeficiency is produced by a variety of causes, including drug use, and the
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establishment argues that the HIV retrovirus is the only cause, becomes a little clearer when we consider it
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in the context of the larger debate between the genetic determinists and the Darwinian adaptationists. I
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will talk about that in more detail in a newsletter on immunodeficiency.
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</p>
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<p>
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The issues of cancer, aging, and "hormone receptors," are also illuminated by seeing the organism as capable
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of adaptive modification of its genes.
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</p>
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<p>
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These newer molecular approaches to the study of biology are vindicating some of the practical observations
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of plant and animal breeders, and terms such as <em>telegony, heterosis,</em> and <em>xenia</em> might come
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into common use again, along with <em>genomic imprinting.
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</em>Here, I want to give examples of "hormonal imprinting" amd "genetic imprinting," and to show how the
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idea of the "retrovirus" or "mobile genetic elements" relates to practical health issues and therapies. The
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developing egg cell is constructed and modified in many ways during its growth. The nurse cells which
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surround it in the ovarian follicle inject massive quantities of material, especially RNA, into the
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expanding egg cell. Regulatory substances and energy production modify enzyme activities and structural
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proteins, which will influence the way it develops after fertilization. During the entire lifetime of the
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individual person, the developing egg cells are open to influences from the organism as a whole. Because of
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the Weismannian scientific culture, it's important to start with a few of the clearest interaction between
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the environment and the reproductive cell, but many other types of interaction are starting to be explored.
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It has been suggested that environmental stress is responsible for viral epidemics, by activating viruses in
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their animal hosts, and causing them to spread to humans. Whether that's true or not, it is well recognized
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that stress causes increased susceptibility to the development of viral infections. It also causes increased
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genetic variability, which is logical in the evolutionary sense, that a species should become more variable
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when its environmental niche has changed. The mobile genetic elements that were first recognized by Barbara
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McClintock are now considered to be the most important means by which stress increases genetic variability.
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In bacteria (J. Cairns<strong>;</strong> Salyers & Shoemaker, 1996), genetic changes are known to occur
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in response to specific substances, which lead to adaptation to that substance. The mobile elements which
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are responsible for the defensive adaptive response to antibiotics are similar to viruses. <strong>In these
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instances, the genetic dogma which has been taught very recently in the universities couldn't have been
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more clearly disproved. So far, the tendency in the United States is to concentrate on the details
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because of their technological potential (for genetic engineering of lucrative products) and to ignore
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the larger biological meaning of this interaction of stress with genetics.
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</strong>
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</p>
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<p>
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Resistance to antibiotics is transmitted to other bacteria by "injecting," during conjugation of a resistant
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bacterium with a sensitive one, a small virus-like granule containing the DNA required for detoxifying the
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antibiotic, along with some adjoining genes. The antibiotic itself, producing stress, stimulates the
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formation of this genetic package. (Whole university courses used to be devoted to showing why such things
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couldn't happen.)
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</p>
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<p>
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The enzymes which cut out sections of DNA are the "restrictases," which are famous for their use in
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identifying samples of DNA. These "endonucleases" are activated by stress. In "excitotoxicity," which kills
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nerve cells through a combination of intense activation with deficient energy stores (i.e., stress), these
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enzymes are activated. In apoptosis, or "programmed cell death," these enzymes are activated, along with
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enzymes which repair the broken genes, and the resulting energy drain from an impossible repair job causes
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the cell's sudden dissolution. Between excitotoxicity and apoptosis, there are intermediate states, in which
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the dissolution is retarded or reversed.
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</p>
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<p>
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When the stress is more generalized, so that the cells survive, the more sensitive sections of DNA are
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rearranged within the cell. Some of them may escape as infective particles.
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</p>
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<p>
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Barbara McClintock wrote about the effects of stress causing genetic rearrangement, and traced the movements
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of the mobile genetic elements. At the same time, without knowing about her work, Leonell Strong was working
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with mice, exploring the role of "genetic instability" in causing cancer, and identifying estrogen and "milk
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particle," or "milk factor," a virus-like particle that interacted with estrogen, as causes of breast
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cancer. With only the elements of <em>stress,</em> the <em>endonucleases,</em> and the <em>mobile packets of
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genes,</em> adaptively increased variability, and the spreading of genes among a population can be
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explained. However, there is a subtler level at which the adaptations acquired by an indiviual can be passed
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on to offspring. This is "imprinting."
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</p>
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<p>
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"Genetic imprinting" is being studied mainly in terms of the covering of regions of DNA with methyl groups.
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This is thought to have evolved as a way to keep the endonucleases from attacking the DNA. Sections of DNA
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that have been methylated can be passed on to offspring in that form, and they can be traced as a pattern of
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gene activity or inactivity. The maternal genes function in a manner identifiably different from the
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paternal genes. Having passed through the mother's body, the genes have been modified.
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</p>
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<p>
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"Hormonal imprinting" refers to the great changes in sensitivity to hormones (and related substances) that
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persist after exposure to that substance early in life. When the mother's hormones are imbalanced during
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pregnancy or nursing, the baby is "imprinted" with an altered sensitivity to hormones. Leonell Strong showed
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that these effects could be exaggerated generation after generation. But--strangely, considering that he was
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a student of T. H. Morgan, who is considered to be the founder of classical genetics--<strong>
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Strong</strong>
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<strong>found that a single treatment, or a series of treatments, with an extract of liver, or with certain
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nucleosides (the units for constructing DNA), could reverse the course of generations of breeding, and
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eliminate the susceptibility to cancer.</strong>
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</p>
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<p>
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<strong> </strong>In modern terms, he was probably working with a combination of genetic imprinting and
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hormonal imprinting. His "milk factor" very probably was one of the "endogenous retroviruses," or mobile
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genetic elements. (However, Gaal, et al., 1998, found that imprinting factors can be transmitted in the
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milk.)
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</p>
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<p>
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Movable genetic elements appear to regulate normal developmental processes (Long, et al., 1998) and the
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introduction of new particles can "improve fitness." This is an aspect of the HIV controversy that has been
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completely ignored, as far as I can tell. Peter Duesberg argues that the presence of antibodies to the HIV
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indicates that the immune system is active, and that there is no evidence showing the virus to be harmful.
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My suggestion would be that the virus is probably present quietly in many people who have no antibodies to
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it, and that environmental toxins and other stressors cause it to be adaptively expressed, creating the
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possibility for an antibody response. The "viral particle" itself might be biologically useful, though this
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wouldn't exclude the possibility that an abnormal immunological response to it could have harmful
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repercussions.
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</p>
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<p>
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The importance of the retroviruses in the human genome hasn't been widely appreciated. ("almost 10%<strong>
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. . .</strong> homology with the retroviruses," Deb, et al, 1998.)
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</p>
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<p>
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Environmental pollution with estrogens and immunosuppressive substances, when it persists throughout the
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developmental period, and across generations, will be dangerous at levels much below those that show an
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immediate hormonal or immunosuppressive effect. Tests that determine the "mutagenicity" or "carcinogenicity"
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of a substance are performed within a context of a theoretical genetics which is demonstrably false<strong
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>;</strong>
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until the complexities of imprinting and transgenerational effects are taken into account, it would be wrong
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to accept the claim that there are "safe levels," or "thresholds of harmful effects."
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</p>
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<p>
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When babies are imprinted by the mother's diuretics, by milk substitutes, and by industrial effluents, the
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worst effects are likely to be seen decades later, or even generations later. There is a simple image that I
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think makes it possible to grasp as a whole the unity of things which have been described as existing on
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different "levels," the genetic, the metabolic, and the ecological. This is the image of an interaction
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between water and large molecules, such as proteins and nucleic acids, with the system--the way the large
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molecule is folded, and the way the water molecules are ordered--having more than one arrangement, or
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physical state, each state differing slightly in the amount of potential energy it contains. Then, the
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differences between respiratory energy (producing carbon dioxide and consuming electron-equivalents), and
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relatively anaerobic conditions, determine the probability that the system will return to its higher energy
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state after it has been perturbed.
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</p>
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<p>
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A brief perturbation amounts to simple perception and response, reflecting the basic "irritability" of life,
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to use Lamarck's term. But with more intense disturbances, the structures are altered at deeper levels, and
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structures will be restored with different degrees of completeness, and the organism will have adapted,
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according to its resources, either toward increased "fitness" and sensitivity, or toward decreased
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sensitivity.
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</p>
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<p>
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On the level of an individual, the movement away from fitness and sensitivity would resemble the development
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of aging and degenerative disease<strong>; </strong>
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on the level of a species, it would amount to "reverse evolution," a mammal would become more reptilian, a
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primate would become more rodent-like.
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</p>
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<p>
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Protective interventions, and therapies, will consist of things which protect the structures (preserving
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sensitivity, while blocking excessive stimulation), and which increase the energy resources. A great variety
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of physiological indicators show that substances such as progesterone, thyroid and carbon dioxide are acting
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"universally" as protectants, in ways that make sense only with some perspective such as this, of the
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systematic changes in the physical state of the living substance.
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<h3>REFERENCES</h3>
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Taruscio D, et al., <strong>
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Human endogenous retroviruses and environmental endocrine disrupters: a connection worth exploring?
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</strong> Teratology. 1998 Aug;58(2):27-8.
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</p>
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<p>
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Taruscio D, et al., <strong>Human endogenous retroviral sequences: possible roles in reproductive
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physiopathology.
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</strong> Biol Reprod. 1998 Oct;59(4):713-24
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</p>
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<p>
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Genome 1998 Oct;41(5):662-8. <strong>A single-primer PCR-based retroviral-related DNA polymorphism shared by
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two distinct human populations.</strong> Deb P, Klempan TA, O'Reilly RL, Singh SM Department of Zoology,
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University of Western Ontario, London, Canada. <strong>"Almost 10% of the human genome consists of DNA
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sequences that share homology with retroviruses.</strong>
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These sequences, which represent a stable component of the human genome <strong>
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(although some may retain the ability to transpose),</strong> remain poorly understood." "Such novel
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polymorphisms should provide useful markers and permit assessment of evolutionary mechanisms associated with
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retroviral-related genomic evolution. "
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</p>
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<p>
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Chromosoma 1991 Dec;101(3):141-56 <strong>Integration site preferences of endogenous retroviruses.</strong>
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Taruscio D, Manuelidis L. Yale Medical School, New Haven, CT 06510. "Retroviruses have the ability to
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integrate into the genome of their host, in many cases with little apparent sequence or site specificity.".
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<strong>"Retroviral elements in Alu-rich domains would be expected to be actively transcribed in all cells.
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Surprisingly, hybridization to blots of brain RNA showed an approximately 25 fold lower level of
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transcripts from these Alu associated elements than from retroviral sequences restricted to later
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replicating, heterochromatic domains." "Each host genome may utilize these elements for contrary, and
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possibly beneficial functions."
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</strong>
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</p>
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<p>
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<strong> </strong>APMIS Suppl 1998;84:37-42 <strong>The potential of integrons and connected programmed
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rearrangements for mediating horizontal gene transfer</strong>.. Sundstrom L. "Site-specific
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recombination of integrons, mediates transfer of single genes in small genomes and plasmids. Recent data
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suggest that new genes are recruited to the cassettes--the units moved by integrons. Integrons are resident
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in a class of transposons with pronounced target selectivity for resolution loci in<strong>
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broad host range plasmids. A resulting network of programmed transfer routes, with potential offshoots
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reaching into eukaryotic cells, may channel genes to unexpectedly remote organisms."
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</strong>"It seems very clear that integrons and associated programmed transfer mechanisms have high
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significance for the dissemination of antibiotic resistance genes in bacteria whereas further studies are
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needed to assess their importance for spreading of arbitrary genes <strong>in a wider range of host
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systems."</strong>
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</p>
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<p>
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Clin Infect Dis 1996 Dec;23 Suppl 1:S36-43. <strong>Resistance gene transfer in anaerobes: new insights, new
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problems.</strong> Salyers AA, Shoemaker NB. <strong>"Integrated gene transfer elements, called
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conjugative transposons, appear to be responsible for much of the transfer of resistance genes among
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Bacteroides species. Conjugative transposons not only</strong> transfer themselves but also mobilize
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|
coresident plasmids and excise and mobilize unlinked integrated elements." "An unusual feature of the
|
|
Bacteroides conjugative transposons is that <strong>transfer of many of them is stimulated considerably by
|
|
low concentrations of antibiotics. Thus, antibiotics not only select for resistant strains but also can
|
|
stimulate transfer of the resistance gene</strong> in the first place."
|
|
</p>
|
|
<p>
|
|
Genetics 1991 Aug;128(4):695-701 <strong>Adaptive reversion of a frameshift mutation in Escherichia
|
|
coli.</strong> Cairns J, Foster PL Department of Cancer Biology, Harvard School of Public Health,
|
|
Boston, Massachusetts 02115. Mutation rates are generally thought not to be influenced by selective forces.
|
|
<strong>This doctrine rests on the results of certain classical studies of the mutations that make bacteria
|
|
resistant to phages and antibiotics.</strong> We have studied a strain of Escherichia coli which
|
|
constitutively expresses a lacI-lacZ fusion containing a frameshift mutation that renders it Lac-. Reversion
|
|
to Lac+ is <strong>a rare event during exponential growth but occurs in stationary cultures when lactose is
|
|
the only source of energy. No revertants accumulate in the absence of lactose, or in the presence of
|
|
lactose if there is another, unfulfilled requirement for growth.</strong> The mechanism for such
|
|
mutation in stationary phase is not known, but it requires some function of RecA which is apparently not
|
|
required for mutation during exponential growth.
|
|
</p>
|
|
<p>
|
|
Science 1993 Oct 15;262(5132):317-319. <strong>Whither directed mutation? </strong>
|
|
Foster, P.L.
|
|
</p>
|
|
|
|
<p>
|
|
Science 1995, 268(5209):418-420. <strong>Adaptive mutation in Escherichia coli: a role for
|
|
conjugation.</strong> Radicella JP, Park PU, Fox, M.S. Nature 1998 Mar 12;392(6672):141-2<strong>
|
|
Are retrotransposons long-term hitchhikers?</strong> Burke WD, Malik HS, Lathe WC 3rd, Eickbush TH.
|
|
</p>
|
|
<p>
|
|
J Biomol Struct Dyn 1998 Feb;15(4):717-21 <strong>Mammalian retroposons integrate at kinkable DNA
|
|
sites.</strong> Jurka J, Klonowski P, Trifonov EN "This suggests that during interaction with the
|
|
endonucleolytic enzyme, or enzymes, DNA undergoes bending at the integration sites and kinks are formed, as
|
|
initial steps in generating the nicks. Nicking at kinkable sites, particularly at TA steps, may also play a
|
|
role in integration of other insertion elements."
|
|
</p>
|
|
|
|
<p>
|
|
J. Mol Evol 1997 Dec;45(6):599-609 <strong>The evolution of MHC diversity by segmental duplication and
|
|
transposition of retroelements.</strong> Kulski JK, Gaudieri S, Bellgard M, Balmer L, Giles K, Inoko H,
|
|
Dawkins RL.
|
|
</p>
|
|
<p>
|
|
Biochemistry (Mosc) 1997 Nov;62(11):1202-5. <strong>Telomerase is a true reverse transcriptase. A
|
|
review.</strong> Cech TR, Nakamura TM, Lingner J Department of Chemistry and Biochemistry, Howard Hughes
|
|
Medical Institute, University of Colorado,Boulder. <strong>"We find it remarkable that the same type of
|
|
protein structure required for retroviral replication is now seen to be essential for normal chromosome
|
|
telomere replication in diverse eukaryotes</strong>."
|
|
</p>
|
|
|
|
<p>
|
|
Gene 1997 Dec 31;205(1-2):177-82 <strong>Mobile elements inserted in the distant past have taken on
|
|
important functions.</strong> Britten RJ.
|
|
</p>
|
|
<p>
|
|
Genetika 1994 Jun;30(6):725-30 <strong>["Adaptive transposition" of retrotransposons in the Drosophila
|
|
melanogaster genome accompanying the increase in features of adaptability].
|
|
</strong> Beliaeva ES, Pasiukova EG, Gvozdev V.A. . "<strong>The transpositions were accompanied by a
|
|
dramatic increase in individual fitness (competitive success)."</strong>
|
|
</p>
|
|
|
|
<p>
|
|
Genetika 1997 Aug;33(8):1083-93 <strong>[Stress induction of retrotransposon transposition in Drosophila:
|
|
reality of the phenomenon, characteristic features, possible role in rapid evolution].</strong>
|
|
Vasil'eva LA, Ratner VA, Bubenshchikova EV "This stress response involved mobilization of retrotransposons."
|
|
<strong>"In all these cases, stress induction of retrotransposon transpositions was mediated by molecular
|
|
mechanisms of the heat shock system-the general system of cell resistance to external and physiological
|
|
stress factors. From the viewpoint of evolution, stress induction of transpositions is a powerful factor
|
|
generating new genetic variation in populations under stressful environmental conditions.</strong>
|
|
Passing through a "bottleneck," a population can rapidly and significantly alter its population norm and
|
|
become the founder of new, normal forms."
|
|
</p>
|
|
|
|
<p>
|
|
Mol Biol (Mosk) 1995 May-Jun;29(3):522-8 <strong>[Conserved regions of potential ORF1 protein products of
|
|
mobile elements and retroviral proteins, encoded by the gag gene].
|
|
</strong> Kanapin AA, Ivanov VA, Il'in IuV.
|
|
</p>
|
|
<p>
|
|
Radiats Biol Radioecol 1995 May-Jun;35(3):356-63 <strong>[DNA analysis of retroposon-like genetic LINE
|
|
elements in blood plasma of rats exposed to radio-diapason electromagnetic waves].</strong> [Article in
|
|
Russian] Belokhvostov AS, Osipovich VK, Veselova OM, Kolodiazhnaia VA<strong>
|
|
The elevation of LINE-elements' DNA level was revealed in blood plasma of rats exposed to
|
|
electromagnetic waves.</strong> The amount of full-size 5'-containing LINE-elements copies was
|
|
increased<strong>
|
|
especially. Connection of this effect with retrotransposon activation and genetic instability condition
|
|
of organism development is supposed.
|
|
</strong>
|
|
</p>
|
|
|
|
<p>
|
|
<strong> </strong>Dokl Akad Nauk 1995 Jan;340(1):138-40 <strong>[Induction of virus-like particles Tu1 by
|
|
the mini-Tu1 element in the SPT3 mutant strain of Saccharomyces cerevisiae].
|
|
</strong> Reznik NL, Zolotova LI, Shuppe NG.
|
|
</p>
|
|
<p>
|
|
Dokl Akad Nauk 1994 Dec;339(6):838-41 <strong>[Extracellular virus-like particles retrotransposon Gypsy (MDG
|
|
4) as an infectivity factor].</strong> Semin BV, Il'in IuV.
|
|
</p>
|
|
<p>
|
|
Mol Biol (Mosk) 1994 Jul-Aug;28(4):813-21.<strong>
|
|
[Expression of the third open reading frame of the drosophila MDG4 retrotransposon similar to the
|
|
retroviral env-genes, occurring through splicing].
|
|
</strong> Avedisov SN, Il'in IuV "The presence of a third long open reading frame (ORF3) is the common
|
|
feature of a number of Drosophila retrotransposons, including MDG4 (gypsy). <strong>Thus, these elements
|
|
have a strong structural resemblance to the integrated forms of vertebrate retroviruses."</strong>
|
|
"The regulation at the level of splicing is supposed to be one of the most important factors controlling the
|
|
transposition frequency of MDG4."
|
|
</p>
|
|
<p>
|
|
Genetika 1994 Jun;30(6):743-8 <strong>[Introduction of a single transpositionally-active copy of MDG4 into
|
|
the genome of a stable line of Drosophila melanogaster causes genetic instability].</strong>
|
|
Liubomirskaia NV, Shostak NG, Kuzin AB, Khudaibergenova BM, Il'in IuV, Kim AI. "A previously described
|
|
system of a Drosophila melanogaster mutative strain (MS), which originates from a stable strain (SS), is
|
|
characterized by genetic instability caused by transposition of the retrotransposon gypsy. New unstable
|
|
strains were obtained by microinjections of the gypsy transposable copy into SS embryos." "Genetic
|
|
instability in the MS system is apparently induced by a combination of two factors: the presence of a gypsy
|
|
transposable copy and mutation(s) in the gene(s) regulating its transpositions."
|
|
</p>
|
|
|
|
<p>
|
|
Genetika 1991 Mar;27(3):404-10 <strong>[Maintenance of the copy number of retrotransposon MDG3 in the
|
|
Drosophila melanogaster genome].</strong> Glushkova IV, Beliaeva ESp, Gvozdev VA The genomes of
|
|
laboratory stocks and natural population of Drosophila melanogaster contain 8-12 copies of retrotransposon
|
|
MDG3 detected by in situ hybridization. Construction of genotypes with decreased MDG3 copy number using
|
|
X-chromosome and chromosome 3 free of MDG3 copies <strong>results in appearance of hybrid genomes carrying
|
|
up to 7-10 copies, instead of 2-4 copies expected.</strong> New MDG3 copies are detected in different
|
|
genome regions, including the 42B hot spot of their location. The chromosomes, where new clusters of MDG3
|
|
were observed, carry conserved "parental pattern" of MDG1 arrangement. <strong>
|
|
The data obtained suggest the existence of genomic mechanism for maintenance of retrotransposon copy
|
|
number on a definite level.</strong>
|
|
</p>
|
|
<p>
|
|
<strong> </strong>Biull Eksp Biol Med 1998 Jul;126(7):4-14 <strong>[The role of retroposition in the
|
|
self-regulation of genome processes (do genes program the body and retroposons program genome]?</strong>
|
|
Bebikhov DV, Postnov AIu, Nikonenko TA.
|
|
</p>
|
|
<p>
|
|
Genetika 1996 Jul;32(7):902-13 <strong>[Analysis of motifs of functional MDG2 sites in assuring its possible
|
|
molecular functions].</strong> Ratner VA, Amikishiev VG "Enhancers of mobile genetic elements are
|
|
assumed to determine modification of adjacent genes and polygenes. <strong>Excisions and transpositions of
|
|
mobile elements seem to be induced by external stress factors or physiological factors through a
|
|
heat-shock system."
|
|
</strong>
|
|
</p>
|
|
<p>
|
|
<strong> </strong>Genomics 1998 Dec 15;54(3):542-55 <strong>A long terminal repeat of the human endogenous
|
|
retrovirus ERV-9 is located in the 5' boundary area of the human beta-globin locus control
|
|
region.</strong> Long Q, Bengra C, Li C, Kutlar F, Tuan D. "Transcription of the human beta-like <strong
|
|
>
|
|
globin genes in erythroid cells</strong> is regulated by the far-upstream locus control region (LCR). In
|
|
an attempt to define the 5' border of the LCR, we have cloned and sequenced 5 kb of new upstream DNA. We
|
|
found an LTR <strong>retrotransposon belonging to the ERV-9 family of human endogenous retroviruses</strong>
|
|
in the apparent 5' boundary area of the LCR." "This LTR is conserved in human and gorilla, indicating its
|
|
evolutionary stability in the genomes of the higher primates. In both recombinant constructs and the
|
|
endogenous human genome, the LTR enhancer and promoter activate the transcription of cis-linked DNA
|
|
preferentially in erythroid cells. <strong>Our findings suggest the possibility that this LTR
|
|
retrotransposon may serve a relevant host function in regulating the transcription of the
|
|
beta-globin</strong> LCR." Copyright 1998 Academic Press.
|
|
</p>
|
|
<p>
|
|
Genetika 1995 Dec;31(12):1605-13 <strong>[Heterologous induction of the retrotransposon Ty1: reverse
|
|
transcriptase plays a key role in initiating the retrotransposition cycle].
|
|
</strong> Reznik NL, Kidgotko OV, Zolotova LI, Shuppe NG A new method was developed to study the mechanism
|
|
of initiation of the retrotransposition cycle: retrotransposons of Drosophila melanogaster, gypsy, copia,
|
|
and 17.6 were expressed in yeast under the control of potent yeast promoters. <strong>
|
|
Expression of retrotransposons induced formation of viruslike particles (VLPs) associated with
|
|
full-length Ty1 RNA and DNA sequences.</strong> This phenomenon was termed heterologous induction.
|
|
<strong>When the gene for reverse transcriptase of human immunodeficiency virus (HIV) was expressed in
|
|
yeast, the same results were obtained. These data allowed us to assume the excess of active reverse
|
|
transcriptase to play the central role in induction of transposition.</strong> Possible mechanisms of
|
|
induction of Ty1 transposition by homologous and heterologous elements are discussed. Hum Exp Toxicol 1998
|
|
Oct;17(10):560-3 <strong>Effect of retinoid (vitamin A or retinoic acid) treatment (hormonal imprinting)
|
|
through breastmilk on the glucocorticoid receptor and estrogen receptor binding capacity of the adult
|
|
rat offspring.</strong> Gaal A, Csaba G. "Hormonal imprinting occurs perinatally when the developing
|
|
receptor and the appropriate hormone meet each other. The presence of related molecules in this critical
|
|
period causes misimprinting. Ligands bound<strong>
|
|
to a member of the steroid-thyroid receptor superfamily can disturb the normal maturation of other
|
|
members of the family,</strong> which is manifested in altered binding capacity of the receptor and
|
|
decreased or increased response of the receptor-bearing cell for life. Excess or absence of the hormone also
|
|
can cause misimprinting." <strong>
|
|
"The results of the experiment call attention to the transmission of imprinter molecules by breastmilk
|
|
to the progenies, which can cause lifelong alterations at receptorial level and points to the human
|
|
health aspect. Possible reasons for the differences between retinol and retinoic acid effects and in the
|
|
sensitivity of receptors are discussed."
|
|
</strong>
|
|
</p>
|
|
<p>
|
|
<strong> </strong>Life Sci 1998;63(6):PL 101-5 <strong>Neonatal vitamin E treatment induces long term
|
|
glucocorticoid receptor changes: an unusual hormonal imprinting effect.</strong> Csaba G, Inczefi-Gonda
|
|
A. "Thousandfold tocopherol did not compete with labeled dexamethasone for their receptors,
|
|
suggesting<strong>
|
|
that neonatal vitamin E imprinting effect was not done at direct receptorial level."</strong>
|
|
</p>
|
|
<p>
|
|
<strong> </strong>J Hypertens 1998 Jun;16(6):823-8 <strong>Female Wistar-Kyoto and SHR/y rats have the same
|
|
genotype but different patterns of expression of renin and angiotensinogen genes.</strong> Milsted A,
|
|
Marcelo MC, Turner ME, Ely DL "Female SHR/y rats have the parental Wistar-Kyoto rat autosomes and X
|
|
chromosomes and have no chromosomes of spontaneously hypertensive rat origin; thus they are genetically
|
|
equivalent to female Wistar-Kyoto rats." "The combination of removing estrogen early in development and
|
|
supplementing the ovariectomized females with testosterone revealed strain differences in response of blood
|
|
pressure." "Differences in regulation of renin-angiotensin system genes between strains may result from
|
|
epigenetic mechanisms such as <strong>genome imprinting</strong> of these genes or of another gene that
|
|
functions as a common regulator of renin and angiotensinogen."
|
|
</p>
|
|
|
|
<p>
|
|
Gen Pharmacol 1998 May;30(5):685-7 <strong>Imprinting of thymic glucocorticoid receptor and uterine estrogen
|
|
receptor by a synthetic steroid hormone at different times after birth.</strong> Csaba G, Inczefi-Gonda
|
|
A. 1. "Single allylestrenol treatment (hormonal imprinting) of 3-day old rats reduced the density of thymus
|
|
glucocorticoid receptors and increased the density of uterus estrogen receptors at adult age." "4. The
|
|
experiments demonstrate that hormonal imprinting can be provoked by allylestrenol not only pre- or
|
|
neonatally, as was done in previous experiments, but also a few days later. The imprintability was lost
|
|
between the 4th and 8th day of life."
|
|
</p>
|
|
<p>
|
|
Gen Pharmacol 1998 May;30(5):647-9 <strong>Fetal digoxin treatment enhances the binding capacity of thymic
|
|
glucocorticoid receptors in adult female rats.</strong> Csaba G, Inczefi-Gonda A. 1. Hormonal imprinting
|
|
is provoked in the perinatal critical period in the presence of the appropriate hormone or molecules similar
|
|
to it. As a consequence of hormonal imprinting, the developing receptor finishes its maturation normally (in
|
|
the presence of the adequate hormone) or abnormally (under the effect of foreign molecules that are able to
|
|
bind to the receptor). 2. Digoxin--which has a steroid character--caused faulty imprinting by treatments at
|
|
the 15th, 17th and 20th days of pregnancy. In the adult (3-month-old) animals, the density of thymic
|
|
glucocorticoid receptors was significantly elevated, whereas the density of uterine estrogen receptors was
|
|
not, without any change in receptor affinity. 3. The experiments call attention to the steroid receptor
|
|
imprinting effect of fetal digoxin treatment that must be considered in regard to this treatment at this
|
|
period and later in regard steroid treatments.
|
|
</p>
|
|
|
|
<p>
|
|
Hum Exp Toxicol 1998 Feb;17(2):88-92 <strong>Transgenerational effect of a single neonatal benzpyrene
|
|
treatment on the glucocorticoid receptor of the rat thymus.</strong> Csaba G, Inczefi-Gonda A. Hormonal
|
|
imprinting is provoked perinatally by the appropriate <strong>hormone on its receptor,</strong>
|
|
causing a life-long adjustment of the connection between the two participants. Faulty imprinting is caused
|
|
by the presence of molecules similar to the hormone in this critical period, which results in a persistent
|
|
alteration of the receptor. In the present experiment the transgenerational imprinting effect of a
|
|
steroid-like environmental pollutant, benzpyrene, on the receptor binding capacity of filial thymic
|
|
dexamethasone and uterine estrogen receptors was studied. The receptor density (Bmax) of the thymic
|
|
glucocorticoid receptors of the males was reduced <strong>up to the third (F2) generation.
|
|
</strong>In females this reduction was observed only in the F1 generation of treated animals. There was no
|
|
change in receptor affinity (Kd). Uterine estrogen receptors were not subjected to transgenerational
|
|
imprinting. The experiments demonstrate (1) the possibility of the <strong>
|
|
transgenerational transmission</strong> of imprinting effect, (2) the differences of steroid receptors
|
|
in different organs, and (3) the differences of male's and female's reactions from this aspect. The results
|
|
call attention to the dangers of perinatal aromatic hydrocarbon exposition to the progeny generations.
|
|
</p>
|
|
|
|
<p>
|
|
Genetika 1994 Apr;30(4):437-44 [Tv1--a new family of Drosophila virilis retrotransposons]. Andrianov BV,
|
|
Shuppe NG.<strong>"The method is based on the hypothesis about the universal character of retrotransposition
|
|
through reverse transcription."</strong>
|
|
</p>
|
|
<p>
|
|
<strong> </strong>Genetika 1990 Mar;26(3):399-411 <strong>[Transpositional bursts and chromosome
|
|
rearrangements in unstable lines of Drosophila].
|
|
</strong> Gerasimova TI, Ladvishchenko AB, Mogila VA, Georgieva SG, Kiselev SL, Maksymiv DV "The phenomenon
|
|
of transpositional bursts--massive simultaneous transpositions of mobile elements belonging to different
|
|
structural classes and accompanied by multiple mutagenesis were earlier described. Although the mechanisms
|
|
of this phenomenon are still unclear, it is obvious now that<strong>
|
|
it embraces total genome and includes not only transpositions of different mobile elements but also
|
|
recombination processes--homologous recombination</strong>
|
|
for LTR's and gene conversion."
|
|
</p>
|
|
|
|
<p>
|
|
Eksp Onkol 1986;8(2):29-32 <strong>
|
|
[Nature of the endogenous retrovirus-like particles of the rat liver].
|
|
</strong>
|
|
Korokhov NP, Pyrinova GB, Kurtsman MIa, Tomsons VP, Salganik RI.
|
|
</p>
|
|
|
|
© Ray Peat Ph.D. 2009. All Rights Reserved. www.RayPeat.com
|
|
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|
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|