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Doug Axe: What the public thinks we know about genes

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From Douglas Axe’s Undeniable,

Consider popular wisdom about genes and DNA. Just as most peole think scientists havefigured out how the brain works, so too they think scientists have figured out how DNA works. By my casual observation, most nonscientists—and some scientists as well—think the blueprint from which every living organism was formed is written on that individual’s genome in the language of genes. Accordingly, geese honk because they have the honk gene, and hyperactive dogs yap because they have the hyperactive-dog gene. Likewise, by this popular view people who can sing or whistle received these abilities by receiving the corresponding genes. The master template for specifying all our attributes became public with the publishing of the human genome, supposedly, so all that remain is to finish the task of assigning traits to genes and to empower very person to read and interpret his or her own personal blueprint.

Coming from that viewpoint, most of us would be shocked to know the actual state of ignorance with respect to DNA. (p. 271) More.

See also: Doug Axe on fear of critical thinking in science

Note: No news blogging till this evening. O’Leary for News’s other alternate day job.

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2 Replies to “Doug Axe: What the public thinks we know about genes

  1. 1
    Origenes says:

    Talbott on DNA:

    According to the usual comparison, it’s as if you had to pack 39 km of extremely thin thread into a tennis ball. Moreover, this thread is divided into 46 pieces (individual chromosomes) averaging, in our tennis-ball analogy, over 0.8 km long. Can it be at all possible not only to pack the chromosomes into the nucleus, but also to keep them from becoming hopelessly entangled?

    This question intrigues me. Is there no physical law that commands chromosomes to become hopelessly entangled? What is the physical explanation for the fact that this does not happen?

    For local regions of a chromosome, this effect of location can be finely tuned to a degree and in ways that currently baffle all attempts at understanding. Spurred by as yet unknown signals and forces, a particular segment of a chromosome will loop out as an open-chromatin “thread” from its primary territory and come together with other looping segments of the same chromosome. This well-aimed movement brings certain genes and regulatory elements together while keeping others apart, and in this way properly coordinated gene expression is brought about. Sometimes the fraternizing genes are separated on their chromosome by tens of millions of nucleotide bases. Such chromosome movements are now known to bring together genes and regulatory sites on different chromosomes as well (12)
    With so much concerted movement going on — not to mention the coiling and packing and unpacking of chromosomes mentioned earlier — how does the cell keep all those “miles of string in the tennis ball” from getting hopelessly tangled? All we can say currently is that we know some of the players addressing the problem. For example, there are enzymes called “topoisomerases” whose task is to help manage the spatial organization of chromosomes. Demonstrating a spatial insight and dexterity that might amaze those of us who have struggled to sort out tangled masses of thread, these enzymes manage to make just the right local cuts to the strands in order to relieve strain, allow necessary movement of genes or regions of the chromosome, and prevent a hopeless mass of knots.
    Some topoisomerases cut just one strand of the double helix, allow it to wind or unwind around the other strand, and then reconnect the severed ends. This alters the supercoiling of the DNA. Other topoisomerases cut both strands, pass a loop of the chromosome through the gap thus created, and then seal the gap again. (Imagine trying this with miles of string crammed into a tennis ball)

  2. 2
    bornagain77 says:

    Talbott on genes and organisms:

    Genes and Organisms: Improvising the Dance of Life – Stephen L. Talbott – Nov. 10, 2015
    Excerpt: The performances of countless cells in your body are redirected and coordinated as part of a global narrative for which no localized controller exists. This redirection and coordination includes a unique choreography of gene expression in each individual cell. Hundreds or thousands of DNA sequences move (or are moved) within vast numbers of cell nuclei, and are subjected to extraordinarily nuanced, locally modulated chemical activity so as to contribute appropriately to bodily requirements that are nowhere codified — least of all in those DNA sequences.,,,
    DNA in its larger matrix
    You may recall from my earlier article, “Getting Over the Code Delusion” (Talbott 2010), that packing DNA into a typical cell nucleus is like packing about 24 miles of very thin, double-stranded string into a tennis ball, with the string cut up (in the normal human case) into 46 pieces, corresponding to our 46 chromosomes.
    To locate a protein-coding gene of typical size within all that DNA is like homing in on a one-half-inch stretch within those 24 miles. Or, rather, two relevant half-inch stretches located on different pieces of string, since we typically have two copies of any given gene. Except that sometimes one copy differs from the other and one version is not supposed to be expressed, or one version needs to be expressed more than the other, or the product of one needs to be modified relative to the other. So part of the job may be to distinguish one of those half-inch stretches from the other. “Decisions” everywhere, it seems.
    But no such decisions are made in a vacuum. As it happens, the chromosome does not consist of a naked DNA double helix. Our DNA, rather, is bound up with a massive, intricate, and dynamic protein-RNA-small molecule complex (called chromatin) that is as fully “informative” for the cell as the DNA sequence itself — and, you might say, much more active and directive.,,,
    the cell, by managing the shifting patterns of the chromatin infrastructure within which DNA is embedded, brings our chromosomes into movement on widely varying scales. These include large looping movements that put particular genes into connection with essential regulatory sequences and with other, related genes (that is, with other one-half inch stretches of our “24 miles of string in a tennis ball”).,,,
    A gene is not in any case the kind of rigidly defined entity one might hope to calculate with. As a functional unit appropriate to current circumstances, it must be cobbled together by the cell according to the needs of the moment. There is no neatly predefined path to follow once the cell has located the “right” half inch or so of string, or once it has done whatever is necessary to bring that locus into proper relation with other chromosomal loci participating in the same “dance”.
    One issue has to do with the fact that there are two strands in the DNA double helix and, starting from any particular point, it is possible to transcibe either of two DNA sequences in either of two directions: “forward” along one strand, or “backward” along the other. This yields two completely different products. One of them is very likely not even a protein-coding RNA, and yet it may still play a vital role in gene expression and in cellular processes more generally.
    And even when the cell would proceed in one particular direction, it must “choose” the exact point in the genetic sequence at which to begin. Different starting points can yield functionally distinct results. “Many studies focusing on single genes have shown that the choice of a specific transcription start site has critical roles during development and cell differentiation, and aberrations in . . . transcription start site use lead to various diseases including cancer, neuropsychiatric disorders, and developmental disorders”.8,,,
    The (protein) enzyme that transcribes DNA into RNA is RNA polymerase12. The enzyme certainly does not work alone, however, and its task is by no means cut-and-dried. To begin with, its critical interactions with various elements of the pre-initiation complex help determine whether and exactly where transcription will begin, if it is to begin at all. Then, after those “decisions” have been made, RNA polymerase moves along the double helix transcribing the sequence of genetic “letters” into the complementary sequence of an RNA.
    Throughout this productive journey, which is called elongation, the RNA polymerase still keeps good and necessary company. Certain co-activators modify it during its transit of a genetic locus, and these modifications not only enable transcription elongation to begin, but also provide binding sites for yet other proteins that will cooperate throughout the transcription journey.,,,
    Finally — and mirroring all the possibilities surrounding initiation of gene transcription — there are the issues relating to its termination. Again, they are far too many to mention here. Transcription may conclude at a more or less canonical terminus, or at an alternative terminus, or it may proceed altogether past the gene locus, even to the point of overlapping what, by usual definitions, would be regarded as a separate gene farther “downstream”. The cell has great flexibility in determining what, on any given occasion, counts as a gene, or transcriptional unit.
    The last part of the transcribed gene is generally non-protein-coding, but nevertheless contains great significance. Examining this region in a single gene, a research team recently identified “at least 35 distinct regulatory elements” to which other molecules can bind.13 Further regulatory potentials arise from yet more binding sites on the customized “tail” that the cell adds to the RNA immediately upon conclusion of its transcription.
    Proteins and other molecules that bind to the various regulatory elements of the non-protein-coding portion of the transcript do so in a context-sensitive manner, where cell and tissue type, phase of the cell cycle, developmental stage, location of the RNA within the cell, and environmental factors, both intra- and extra-cellular, may all play a role. These converging influences can change the stability of the RNA, change its localization within the cell, and change the efficiency of its translation into protein, among other possibilities.,,,
    What is generally considered the post-transcriptional modulation of gene expression actually begins during transcription proper. A prime example has to do with what happens partly as a result of the pauses during elongation.
    Cells don’t just passively accept the RNAs that emerge from the transcription process, but rather “snip and stitch” them via an elaborate procedure known as RNA splicing. It happens that the cutting out and knitting together of selected pieces typically begins before the RNA is fully transcribed, and the rhythm of pauses during elongation has an important influence upon which pieces form the mature transcript.
    This splicing operation, which is applied to nearly all human RNAs, is performed by the spliceosome, consisting of a few non-protein-coding RNAs and over 300 cooperating proteins, and is hardly less exacting in its requirements than, say, brain surgery.
    For the vast majority of human genes the operation can be performed in different ways, yielding distinct proteins (called isoforms) from a single RNA derived from a single DNA sequence. This is called alternative splicing, and it would be hard to find anything in human development, disease etiology, or normal functioning that is not dependent in one way or another on the effectiveness of this liberty the cell takes with its gene products.
    But RNA splicing is hardly the end of it. Through RNA editing the cell can add, delete, or substitute individual “letters” of the RNA sequence.15 Or, leaving the letters in place, the cell can chemically modify them in any of over one hundred different ways.16 ,,,
    Eventually, a protein-coding RNA needs to be translated into protein. This happens by means of large molecular complexes called “ribosomes”. Just as with gene transcription, there are many associated factors that must work together to bring about the initiation of translation, many that cooperate with the ribosome during translation, and yet others that play a role in modifying, localizing, or otherwise regulating the newly produced protein.
    The overall picture of gene expression is one of unsurveyable complexity in the service of remarkably effective living processes.,,,
    A decisive problem for the classical view of DNA is that “as cells differentiate and respond to stimuli in the human body, over one million different proteins are likely to be produced from less than 25,000 genes”.30 Functionally, in other words, you might say that we have over a million genes.,,,

    Or to put it more simply:

    “The genome is an ‘organ of the cell’, not its dictator”
    – Denis Noble – President of the International Union of Physiological Sciences

    Ask an Embryologist: Genomic Mosaicism – Jonathan Wells – February 23, 2015
    Excerpt: humans have a “few thousand” different cell types. Here is my simple question: Does the DNA sequence in one cell type differ from the sequence in another cell type in the same person?,,,
    The simple answer is: We now know that there is considerable variation in DNA sequences among tissues, and even among cells in the same tissue. It’s called genomic mosaicism.
    In the early days of developmental genetics, some people thought that parts of the embryo became different from each other because they acquired different pieces of the DNA from the fertilized egg. That theory was abandoned,,,
    ,,,(then) “genomic equivalence” — the idea that all the cells of an organism (with a few exceptions, such as cells of the immune system) contain the same DNA — became the accepted view.
    I taught genomic equivalence for many years. A few years ago, however, everything changed. With the development of more sophisticated techniques and the sampling of more tissues and cells, it became clear that genetic mosaicism is common.
    I now know as an embryologist,,,Tissues and cells, as they differentiate, modify their DNA to suit their needs. It’s the organism controlling the DNA, not the DNA controlling the organism.

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