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<h1>Estrogen, memory and heredity: Imprinting and the stress response</h1>
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<p class="nav"><span class="nav-left">Listed under <a href="/ray-peat.html">Ray Peat</a>.</span><span class="nav-right"><a href="/theme.html">Theme</a></span></p>
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<p>From the <a href="https://raypeat.com/articles/articles/imprinting.shtml" target="_blank">original article</a> in 2009. Author: <a href="https://raypeat.com/" target="_blank">Ray Peat</a>.</p>
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<p>
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Stresses, including estrogen excess, activate the Heat Shock Proteins
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(HSP), the stress-proteins, a primitive defense system. </p><p>
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Heat Shock Proteins and "hormone receptors" are closely related
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and interdependent. </p><p>
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Stress (at least partly via HSP) activates viral expression, ordinary
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gene expression, and destabilizes the genome, activating the "endonucleases,"
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enzymes which break up DNA chains. </p><p>
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Stress increases genetic variability. </p><p>
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DNA chains can be chemically modified (e.g., methylated) in a way that
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limits enzymes' accesss, probably as protection, and to regulate gene
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expression. </p><p>
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Genes, and subsequent growth and development, are modified by the prenatal
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hormonal environment, that of the newborn, and even that of the parents
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before conception. </p><p>
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<em>Genomic imprinting</em> makes maternal genes behave differently from
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paternal genes. </p><p>
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<em>Hormonal imprinting</em> early in life sets the pattern of expression
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of genes. </p><p>
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"Crossing-over" intermixes the genes on the chromosomes as
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cells multiply. </p><p>
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Stresses and regulatory substances can change the patterns of gene expression
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that define cell types. </p><p>
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"Stem cells" are those capable of renewing tissues, and may
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be "pluripotent," able to become glial cells and neurons in
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the brain, or, in the bone marrow, to become red blood cells or white
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blood cells, depending on regulatory influences. </p><p>
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"Cloning" animals from body cells strongly suggests that any
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cell is potentially totipotent, able to differentiate into any other
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type of cell. </p><p>
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We are "imprinted" by our mothers' hormonal and nutritional
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conditions, but we can intervene to correct these "inherited"
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conditions, by maintaining optimal hormonal and nutritional balances. </p><p>
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Recent work in several areas of biology is showing that heredity is
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not rigidly deterministic, in the way implied by traditional genetics,
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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
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don't involve the mechanistic interventions of "gene therapy"
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or "genetic engineering." </em> For example, nontoxic treatments
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for cancer that were demonstrated decades ago, were discarded because
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they didn't seem consistent with "genetics." Many problems
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that are classified as congenital or genetic, turn out to be physiological,
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and correctable. Even the brain and the heart, which until recently
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were considered to be incapable of regenerative repair, are now seen
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to be capable of great anatomical flexibility.</p>
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<p>
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There are still great authoritarian forces opposed to recognizing, and
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supporting, the organism's full potential. <strong>The most useful therapies
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will remain in obscurity until many people see that those therapies
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have a firmer scientific foundation than orthodox (antiquated) medical
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genetics has. </p>
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<p>
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</strong>Over 100 years ago, Samuel Butler had an argument with Charles Darwin,
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and concluded that Darwin was philosophically muddled, and dishonest.
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Butler was annoyed that Darwin had belittled the work of his predecessors,
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including his grandfather, Erasmus Darwin. Butler was defending the
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idea of biological intelligence, the incorporation of experience into
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physiology and heredity.</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
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by the fact that in his introduction, Darwin was careful to point out
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that <em>his ideas were already being misrepresented, and that he did
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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
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and the inheritance of acquired traits. I suppose those remarks might
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have been motivated partly by knowing that Butler didn't approve of
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the way he was behaving, but they didn't seem to have much influence
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on the way history has characterized Darwin's work. All of my biology
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professors would have been happier if Darwin had never made those remarks.
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I suspect 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
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relatively minor issue of how evolution works. </p><p>
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After Darwin's death, the study of heredity made some strange concessions
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to the culture of anti-evolutionism. As people began thinking about
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"particles that carry heredity," the "genes," ideas
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from the anti-evolutionist culture formed much of the context for understanding
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these "particles." </p>
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<p>
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Darwin had suggested that the mature organism reconstitutes itself in
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the germ cells, by sending gemmules or pangens (buds or sprouts or derivatives)
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from its various parts, so that the parent's traits would be incorporated
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into the reproductive cells. This was called pangenesis, meaning that
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the whole organism was the source for the new offspring. This theory
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opened the possibility for newly acquired traits to be passed on. It
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grew out of the experience of animal breeders and horticulturists, who
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were dedicated to improving their breeds and strains, <em>by selecting
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the best individuals grown under the best conditions. </em> It was known
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that the miniature ponies, <strong>Shetlands for example, would grow larger
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each generation when bred under favorable conditions of domestication,
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rather than under the harsh conditions of their native island. </strong> It
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apparently never occurred to most plant and animal breeders that they
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might be able to <em>improve</em> a breed by subjecting it to harmful
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conditions. </p><p>
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Around the end of the 19th century, August Weismann began a systematic
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attack on the ideas of Darwin. As part of his campaign, he invented
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the doctrine that the reproductive cells are absolutely isolated from
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the rest of the organism, and that they are immortal. The rest of the
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organism is built up by the <em>deletion</em> of genetic information.
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This doctrine was very convenient for those who maintained that all
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organisms had been created in a single moment, and that the <em>appearance</em>
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of evolution resulted from the extinction of some species, but not the
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new appearance of some species. Some people, reasoning from Weismannism,
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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
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Weismann's theory of the developing individual. Bacteria, in that view,
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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
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of that primeval genetic information. </p>
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<p>
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The changes produced by <em>subtraction</em> were compatible with the
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notion of fallen man in a corrupt world, while the <em>addition</em> of
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heritable traits through experience would connote a sharing in the process
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of creation. The hereditary particles making up Weismann's "immortal
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isolated germ line" connoted a single original creation.</p>
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<p>
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As mutations in the genes came to be seen as a reality, experiments
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with X-rays suggested to some that all mutations were harmful, and this
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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
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what seemed to be meaningfully <em>directed</em> mutations, the doctrine
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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
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increases, excluded acts of creation from the fallen material world.)
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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
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trait. </p>
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<p>
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I think anyone who reads the "landmark publications" in genetics
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will see that genetics had very little to do with scientific method,
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as commonly conceived, and that it had all the traits of a cult. Analysis
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of the language of genetics reveals that terms have more often been
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used to cover up empty speculation than to clarify situations of fact.</p>
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<p>
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Parallel to the way Darwin infuriated Samuel Butler by misrepresenting
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the origins of his theory, the neodarwinists who debate the creationists
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over school textbooks are ignoring the ways in which the culture of
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antievolutionism shaped their own view of genetics. </p><p>
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The discovery of enzymes that produce DNA modeled on RNA, "reverse
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transcriptases," began undermining traditional genetics, because
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it showed that new information can enter our genome. </p><p>
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The discovery that bacteria can pass "genes" from one individual
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to another, conferring antibiotic resistance upon previously sensitive
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strains, was a major nuisance to people working in infectious disease,
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since it complicates the treating of disease, but it indicated that
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"evolution," or genetic change, was capable of happening in
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non-random ways. </p><p>
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Early in the study of viral genetics, many people realized that "organisms"
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which can't reproduce without their relatively complex hosts, presented
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a problem for evolutionary theory. If the virus requires a cell in order
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to exist, it is hardly a separate organism. A few people suggested that
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viruses were, or were based on, functional normal parts of higher organisms.
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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.
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Mobile genetic elements are now well recognized, operating within cells,
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and it is common laboratory practice to use viral particles to transfer
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genetic material from one cell to another.</p>
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<p>
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Cellular systems which cut and splice nucleic acids, creating sequences
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of information which don't exist in the inherited chromosomes, are now
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accepted parts of cell biology. Hormonal and environmental influences
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on the stability of messenger RNA, and on mobile genetic elements, and
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on genomic stability in general, are recognized. <strong><em>The center of
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gravity in the study of the nucleic acids has now shifted from heredity
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to development. </p><p>
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</em>Almost nothing remains of Weismannism, which was the foundation
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of neodarwinism. The "isolation of the germline" doctrine
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persists in a few places, such as explaining why "the ovary runs
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out of eggs," despite some examples of egg-cell renewal.</strong></p>
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<p><strong>
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But when the identity of "germline cells" is found to depend
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on signals from the environment, the last vestige of Weismannian germ-line
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doctrine disappears.</strong> The only meaning of "germline" is
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that some cells are destined to be germ cells, and the meaning disappears
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when such cells differentiate to form body parts. (see Donovan, 1998,
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Labosky, et al., 1994.)</p>
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<p>
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The difference between primordial germ cells and embryonic cells is
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a matter of "imprinting," the process in which a hormone or
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"growth factor" or other "signal" directs a cell
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down a certain course of differentiation. "Imprinting" is
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where genetics and physiology, phylogeny and ontoneny, come together,
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and the new facts that are being discovered are removing the last vestige
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of scientific content from Weismannism/neodarwinism. </p><p>
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The argument between Peter Duesberg and the virus establishment, in
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which Duesberg argues that acquired immunodeficiency is produced by
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a variety of causes, including drug use, and the establishment argues
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that the HIV retrovirus is the only cause, becomes a little clearer
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when we consider it in the context of the larger debate between the
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genetic determinists and the Darwinian adaptationists. I will talk about
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that in more detail in a newsletter on immunodeficiency.</p>
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<p>
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The issues of cancer, aging, and "hormone receptors," are
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also illuminated by seeing the organism as capable of adaptive modification
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of its genes.</p>
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<p>
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These newer molecular approaches to the study of biology are vindicating
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some of the practical observations of plant and animal breeders, and
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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. </p><p>
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</em>Here, I want to give examples of "hormonal imprinting"
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amd "genetic imprinting," and to show how the idea of the
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"retrovirus" or "mobile genetic elements" relates
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to practical health issues and therapies. The developing egg cell is
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constructed and modified in many ways during its growth. The nurse cells
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which surround it in the ovarian follicle inject massive quantities
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of material, especially RNA, into the expanding egg cell. Regulatory
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substances and energy production modify enzyme activities and structural
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proteins, which will influence the way it develops after fertilization.
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During the entire lifetime of the individual person, the developing
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egg cells are open to influences from the organism as a whole. Because
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of the Weismannian scientific culture, it's important to start with
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a few of the clearest interaction between the environment and the reproductive
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cell, but many other types of interaction are starting to be explored. </p><p>
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It has been suggested that environmental stress is responsible for viral
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epidemics, by activating viruses in their animal hosts, and causing
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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
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infections. It also causes increased genetic variability, which is logical
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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
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that were first recognized by Barbara McClintock are now considered
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to be the most important means by which stress increases genetic variability. </p><p>
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In bacteria (J. Cairns<strong>;</strong> Salyers & Shoemaker, 1996), genetic
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changes are known to occur in response to specific substances, which
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lead to adaptation to that substance. The mobile elements which are
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responsible for the defensive adaptive response to antibiotics are similar
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to viruses. <strong>In these instances, the genetic dogma which has been
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taught very recently in the universities couldn't have been more clearly
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disproved. So far, the tendency in the United States is to concentrate
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on the details because of their technological potential (for genetic
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engineering of lucrative products) and to ignore the larger biological
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meaning of this interaction of stress with genetics. </strong> </p>
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<p>
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Resistance to antibiotics is transmitted to other bacteria by "injecting,"
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during conjugation of a resistant bacterium with a sensitive one, a
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small virus-like granule containing the DNA required for detoxifying
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the antibiotic, along with some adjoining genes. The antibiotic itself,
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producing stress, stimulates the formation of this genetic package.
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(Whole university courses used to be devoted to showing why such things
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couldn't happen.)</p>
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<p>
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The enzymes which cut out sections of DNA are the "restrictases,"
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which are famous for their use in identifying samples of DNA. These
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"endonucleases" are activated by stress. In "excitotoxicity,"
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which kills nerve cells through a combination of intense activation
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with deficient energy stores (i.e., stress), these enzymes are activated. </p><p>
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In apoptosis, or "programmed cell death," these enzymes are
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activated, along with enzymes which repair the broken genes, and the
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resulting energy drain from an impossible repair job causes the cell's
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sudden dissolution. Between excitotoxicity and apoptosis, there are
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intermediate states, in which the dissolution is retarded or reversed.</p>
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<p>
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When the stress is more generalized, so that the cells survive, the
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more sensitive sections of DNA are rearranged within the cell. Some
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of them may escape as infective particles.</p>
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<p>
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Barbara McClintock wrote about the effects of stress causing genetic
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rearrangement, and traced the movements of the mobile genetic elements.
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At the same time, without knowing about her work, Leonell Strong was
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working with mice, exploring the role of "genetic instability"
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in causing cancer, and identifying estrogen and "milk particle,"
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or "milk factor," a virus-like particle that interacted with
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estrogen, as causes of breast cancer. </p><p>
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With only the elements of <em>stress,</em> the <em>endonucleases,</em> and
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the <em>mobile packets of genes,</em> adaptively increased variability,
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and the spreading of genes among a population can be explained. However,
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there is a subtler level at which the adaptations acquired by an indiviual
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can be passed on to offspring. This is "imprinting."</p>
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<p>
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"Genetic imprinting" is being studied mainly in terms of the
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covering of regions of DNA with methyl groups. This is thought to have
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evolved as a way to keep the endonucleases from attacking the DNA. Sections
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of DNA that have been methylated can be passed on to offspring in that
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form, and they can be traced as a pattern of gene activity or inactivity.
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The maternal genes function in a manner identifiably different from
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the paternal genes. Having passed through the mother's body, the genes
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have been modified.</p>
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<p>
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"Hormonal imprinting" refers to the great changes in sensitivity
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to hormones (and related substances) that persist after exposure to
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that substance early in life. When the mother's hormones are imbalanced
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during pregnancy or nursing, the baby is "imprinted" with
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an altered sensitivity to hormones. Leonell Strong showed that these
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effects could be exaggerated generation after generation. But--strangely,
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considering that he was a student of T. H. Morgan, who is considered
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to be the founder of classical genetics--<strong> Strong</strong> <strong>found that
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a single treatment, or a series of treatments, with an extract of liver,
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or with certain nucleosides (the units for constructing DNA), could
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reverse the course of generations of breeding, and eliminate the susceptibility
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to cancer.</strong></p>
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<p>In modern terms, he was probably working with a combination of genetic
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imprinting and hormonal imprinting. His "milk factor" very
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probably was one of the "endogenous retroviruses," or mobile
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genetic elements. (However, Gaal, et al., 1998, found that imprinting
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factors can be transmitted in the milk.)</p>
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<p>
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Movable genetic elements appear to regulate normal developmental processes
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(Long, et al., 1998) and the introduction of new particles can "improve
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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
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the presence of antibodies to the HIV indicates that the immune system
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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
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many people who have no antibodies to it, and that environmental toxins
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and other stressors cause it to be adaptively expressed, creating the
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possibility for an antibody response. The "viral particle"
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itself might be biologically useful, though this wouldn't exclude the
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possibility that an abnormal immunological response to it could have
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harmful repercussions. </p>
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<p>
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The importance of the retroviruses in the human genome hasn't been widely
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appreciated. ("almost 10%<strong> . . .</strong> homology with the retroviruses,"
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Deb, et al, 1998.)</p>
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<p>
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Environmental pollution with estrogens and immunosuppressive substances,
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when it persists throughout the developmental period, and across generations,
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will be dangerous at levels much below those that show an immediate
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hormonal or immunosuppressive effect. Tests that determine the "mutagenicity"
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or "carcinogenicity" of a substance are performed within a
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context of a theoretical genetics which is demonstrably false<strong>;</strong>
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until the complexities of imprinting and transgenerational effects are
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taken into account, it would be wrong to accept the claim that there
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are "safe levels," or "thresholds of harmful effects."</p>
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<p>
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When babies are imprinted by the mother's diuretics, by milk substitutes,
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and by industrial effluents, the worst effects are likely to be seen
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decades later, or even generations later. </p><p>
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There is a simple image that I think makes it possible to grasp as a
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whole the unity of things which have been described as existing on different
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"levels," the genetic, the metabolic, and the ecological.
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This is the image of an interaction between water and large molecules,
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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
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more than one arrangement, or physical state, each state differing slightly
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in the amount of potential energy it contains. Then, the differences
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between respiratory energy (producing carbon dioxide and consuming electron-equivalents),
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and relatively anaerobic conditions, determine the probability that
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the system will return to its higher energy state after it has been
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perturbed.</p>
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<p>
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A brief perturbation amounts to simple perception and response, reflecting
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the basic "irritability" of life, to use Lamarck's term. But
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with more intense disturbances, the structures are altered at deeper
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levels, and structures will be restored with different degrees of completeness,
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and the organism will have adapted, according to its resources, either
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toward increased "fitness" and sensitivity, or toward decreased
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sensitivity.</p>
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<p>
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On the level of an individual, the movement away from fitness and sensitivity
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would resemble the development of aging and degenerative disease<strong>; </strong>
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on the level of a species, it would amount to "reverse evolution,"
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a mammal would become more reptilian, a primate would become more rodent-like.</p>
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<p>
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Protective interventions, and therapies, will consist of things which
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protect the structures (preserving sensitivity, while blocking excessive
|
|
stimulation), and which increase the energy resources. A great variety
|
|
of physiological indicators show that substances such as progesterone,
|
|
thyroid and carbon dioxide are acting "universally" as protectants,
|
|
in ways that make sense only with some perspective such as this, of
|
|
the systematic changes in the physical state of the living substance. </p>
|
|
<h2>References</h2>
|
|
<small>
|
|
<p>
|
|
Taruscio D, et al., <strong>
|
|
Human endogenous retroviruses and environmental endocrine disrupters:
|
|
a connection worth exploring? </strong> Teratology. 1998 Aug;58(2):27-8. </p>
|
|
<p>
|
|
Taruscio D, et al., <strong>Human endogenous retroviral sequences: possible
|
|
roles in reproductive physiopathology. </strong> Biol Reprod. 1998 Oct;59(4):713-24</p>
|
|
<p>
|
|
Genome 1998 Oct;41(5):662-8. <strong>A single-primer PCR-based retroviral-related
|
|
DNA polymorphism shared by two distinct human populations.</strong> Deb P,
|
|
Klempan TA, O'Reilly RL, Singh SM Department of Zoology, University
|
|
of Western Ontario, London, Canada. <strong>"Almost 10% of the human
|
|
genome consists of DNA sequences that share homology with retroviruses.</strong>
|
|
These sequences, which represent a stable component of the human genome <strong>
|
|
(although some may retain the ability to transpose),</strong> remain poorly
|
|
understood." "Such novel polymorphisms should provide useful
|
|
markers and permit assessment of evolutionary mechanisms associated
|
|
with retroviral-related genomic evolution. "</p>
|
|
<p>
|
|
Chromosoma 1991 Dec;101(3):141-56 <strong>Integration site preferences of
|
|
endogenous retroviruses.</strong> Taruscio D, Manuelidis L. Yale Medical
|
|
School, New Haven, CT 06510. "Retroviruses have the ability to
|
|
integrate into the genome of their host, in many cases with little apparent
|
|
sequence or site specificity.". <strong>"Retroviral elements in
|
|
Alu-rich domains would be expected to be actively transcribed in all
|
|
cells. Surprisingly, hybridization to blots of brain RNA showed an approximately
|
|
25 fold lower level of transcripts from these Alu associated elements
|
|
than from retroviral sequences restricted to later replicating, heterochromatic
|
|
domains." "Each host genome may utilize these elements for
|
|
contrary, and possibly beneficial functions." </strong></p>
|
|
<p>APMIS Suppl 1998;84:37-42 <strong>The potential of integrons and connected
|
|
programmed rearrangements for mediating horizontal gene transfer</strong>..
|
|
Sundstrom L. "Site-specific recombination of integrons, mediates
|
|
transfer of single genes in small genomes and plasmids. Recent data
|
|
suggest that new genes are recruited to the cassettes--the units moved
|
|
by integrons. Integrons are resident in a class of transposons with
|
|
pronounced target selectivity for resolution loci in<strong> broad host range
|
|
plasmids. A resulting network of programmed transfer routes, with potential
|
|
offshoots reaching into eukaryotic cells, may channel genes to unexpectedly
|
|
remote organisms." </strong>"It seems very clear that integrons
|
|
and associated programmed transfer mechanisms have high significance
|
|
for the dissemination of antibiotic resistance genes in bacteria whereas
|
|
further studies are needed to assess their importance for spreading
|
|
of arbitrary genes <strong>in a wider range of host systems."</strong> </p>
|
|
<p>
|
|
Clin Infect Dis 1996 Dec;23 Suppl 1:S36-43. <strong>Resistance gene transfer
|
|
in anaerobes: new insights, new problems.</strong> Salyers AA, Shoemaker
|
|
NB. <strong>"Integrated gene transfer elements, called conjugative transposons,
|
|
appear to be responsible for much of the transfer of resistance genes
|
|
among Bacteroides species. Conjugative transposons not only</strong> transfer
|
|
themselves but also mobilize 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.</p>
|
|
<p>
|
|
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>
|
|
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>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>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. </p>
|
|
<p>
|
|
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>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>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>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>
|
|
</small>
|
|
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